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Dr. Jay Duker joins the program to discuss his transition from chair of an ophthalmology department to President & CEO of Eyepoint Pharmaceuticals.Disclosures: Dr. Duker is President & CEO of Eyepoint Pharmaceuticals. Dr. Sridhar has consulted for Eyepoint Pharmaceuticals.You can claim CME credits for prior episodes via the AAO website. Visit https://www.aao.org/browse-multimedia?filter=Audi

In the second part of this two-part series, we continue our discussion with Drs. Eric Suhler and George Mount regarding the use of biologics for the management of non-infectious uveitis.Disclosures:Dr. Suhler has consulted for Abbvie

In the first part of this two-part series, we are joined by Drs. Eric Suhler and George Mount to discuss the use of biologics for the management of non-infectious uveitis.Disclosures:Dr. Suhler has consulted for Abbvie

JCO PO author Dr. Amar U. Kishan, Professor, Executive Vice Chair, and Chief of Genitourinary Oncology Service in the Department of Radiation Oncology at the University of California, Los Angeles, shares insights into his JCO PO article, “Transcriptomic Profiling of Primary Prostate Cancers and Nonlocalized Disease on Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography: A Multicenter Retrospective Study.”  Host Dr. Rafeh Naqash and Dr. Kishan discuss the relationship between Decipher genomic classifier scores and prostate-specific membrane antigen (PSMA) PET/CT-based metastatic spread. TRANSCRIPT Dr. Rafeh Naqash: Hello and welcome to JCO Precision Oncology Conversations, where we bring you engaging conversations with authors of clinically relevant and highly significant JCO articles. I'm your host, Dr. Rafeh Naqash, Assistant Professor at the OU Health Stephenson Cancer Center at the University of Oklahoma. Today we are joined by Dr. Amar Kishan, Executive Vice Chair of the Department of Radiation Oncology at the David Geffen School of Medicine at UCLA and UCLA Jonsson Comprehensive Cancer Center, and also the corresponding and senior author of the JCO Precision Oncology article entitled, “Transcriptomic Profiling of Primary Prostate Cancers and Non Localized Disease on Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography/Computed Tomography: A Multicenter Retrospective Study.” Dr. Kishan, welcome to our podcast and thank you for joining us today. Dr. Amar Kishan: Thank you so much for that kind introduction and the invitation to be here today. Dr. Rafeh Naqash: Well, it seems to me that there's a theme that people in the GU space, investigators in the GU space, are very interested in trying to understand risk predictors for prostate cancer. We had somebody, I believe from Huntsman Cancer Center a few months back on a previous podcast, where they were trying to do risk prediction modeling as well. Could you tell us why that's something that the GU community is very interested in? What's the background? Is it because there's no risk prediction approaches currently? And would this somehow influence management in the near future? Dr. Amar Kishan: Yeah, that's a great question. So, I think this goes back to the point that we're in the era of precision medicine now, and many cancers have these molecular stratification scores and all that. Prostate cancer has lagged a little bit behind in that regard, despite the fact that it's such a common cancer that affects so many people across the country and across the world. So, we do have risk stratification schemes for prostate cancer. These are based off clinical and pathologic variables, like the level of PSA, the size of the tumor on digital rectal examination, now, we're incorporating MRI imaging as well, and then what the cancer looks like under the microscope, the Gleason score. And now there have been revisions to the Gleason score, but it's really kind of the architecture, what the biopsy looks like. And this was kind of developed many, many years ago by Donald Gleason, a pathologist at the VA. What we're not necessarily taking into account routinely is kind of the biology of the cancer per se. You know, what are the molecular drivers? How could that influence ultimate outcome? And that's very important because we have these risk groups, low risk, very low risk, favorable intermediate risk, unfavorable intermediate risk, high risk, very high risk. But within each of those groups, based on the clinical kind of pathological characteristics, there's a huge heterogeneity in outpatients too, and our treatments are effective, but they can be morbid. Putting someone on hormone therapy for an extended period of time has a lot of side effects. Dose escalating radiotherapy or doing surgery and then radiation afterwards, these are big things that have a big impact on the patient, and I think we really need better risk stratification tools to understand who needs intensification and who we can de-escalate treatment for. Dr. Rafeh Naqash: I think those are absolutely valid points, perhaps not just for prostate cancer, more so for all cancers that we currently treat, especially in the current day and age, where we have a tendency to add more and more therapies, combination therapies for patients, and as you mentioned, risk stratification to help identify high risk versus low risk, where you can de intensify treatment, is of high value from a patient standpoint as well as from a financial toxicity standpoint. So then, going to this next part of the approach that you used, and from what I understand in this paper, you had the radiological aspect, which is the PSMA PET, which we'll talk about. Then you had the genomic aspect, where you did some genomic risk-based stratification. Then you had the transcriptomic score based on the Decipher score. So, could you go into some of the details, first, for the PSMA PET, when is it used? What is the utilization? What is it based on, the science behind the PSMA PET? And then we can talk about some of the other genomic transcriptomic predictors that you use in this study. Dr. Amar Kishan: Sure. Absolutely. So, a PSMA PET is an advanced molecular imaging tool. PSMA stands for prostate specific membrane antigen. It's a membrane protein that is expressed on the surface of prostate cancer cells. It is expressed elsewhere in the body as well. The utilization of this for imaging has been a revolution in the staging of prostate cancer, both upfront and in the recurrent setting. We basically had fairly recent approval for PSMA PET being used more routinely in upfront staging and recurrent staging in 2022. Essentially, what this is it gives us an ability to detect whether prostate cancer has spread at a time of diagnosis or try to localize the recurrence. Now, no imaging test is perfect, of course, and a PET has a resolution of about 3 mm. There are questions about the sensitivity of the PET. You get it on a patient with high-risk disease, the PET is negative; you do surgery, there are positive lymph nodes. That can happen, but it's far superior to the tools that we have had before. For instance, beforehand, all we would have is a contrast enhanced CT, bone scan, and MRI. And the sensitivity of those is far below that of a PSMA PET. And that has actually been shown in a randomized trial called the ProPSMA trial out of Australia, where they compared conventional upfront imaging versus PSMA upfront imaging with a crossover design, and there was better detection of disease with the PSMA PET. So that's been a revolution in how we stage prostate cancer. But I'm sure many of your listeners and others are aware of the concerns. When you get a new test and you're detecting disease that's extra prostatic, for instance, are you seeing truly significant new disease that we do need to change our management for, or are we just seeing stuff that wasn't there before that actually wouldn't impact anything? And what I mean by that is, let's say you're seeing things that would never have made a difference to the patient, but now you're saying they have metastatic disease. You're changing their entire treatment paradigm, all kinds of things like that. There's implications to this that hasn't been fully fleshed out. But very recently, like we're talking in July of 2024, essentially, there was a Lancet Oncology paper that looked at the long-term prognosis of patients who had extra prostatic disease on PSMA PET, judged by something called a PROMISE score, kind of gives a quantification on the volume of disease, the brightness of disease, and they correlated that with long term outcomes. And that was really the first time that we have long term follow up data that this extra prostatic disease on PSMA PET actually is prognostically important. So, we're getting there. I mean, now that it's approved and, in some sense, the cat is out of the bag, patients are coming in asking for a PSMA PET, etc. I'm sure everyone has experienced that, but I think we now do have good evidence that it actually is prognostically important as well. Dr. Rafeh Naqash: Thank you for that explanation. And again, to put this into context for things that I've seen and that might also help the listeners in other tumors, so, for example, melanoma surveillance tends to be or while on treatment, patients tend to have more PET scans than what you see, maybe in individuals with lung cancer, where you get a baseline PET and then you have follow up CT scan based imaging is that something that you guys have shifted from in the prostate cancer space with the approval for PSMA PET, where follow up imaging, whether patient is on treatment or surveillance imaging, is PSMA PET based? Dr. Amar Kishan: Yeah, that's a good question. I think there's actually less robust data to support it as a means of treatment response. But in terms of evaluating a recurrence, then, yes, that has become kind of a standard tool. It's very complicated because all of the metrics that we have for, say, a treatment failing are based on conventionally detected metastases or something that shows up on a CT or bone scan. So, again, that question arises if someone is on systemic therapy and then you see something on a PSMA PET, are you going to abandon the therapy that you're on? It technically would be earlier than you would otherwise have done that, or what are you going to do? So, that hasn't been fully fleshed out, but it is used in that circumstance. So, I'd say less for treatment monitoring and more for evaluation of suspected recurrence. Dr. Rafeh Naqash: Understood. And I'm guessing, as a futuristic approach, somebody out there may perhaps do a trial using PSMA PET based imaging to decide whether treatment change needs to be made or does not need to be made. Dr. Amar Kishan: Yeah. It is being incorporated into trials as we speak, I think. Dr. Rafeh Naqash: Now, going to the second part of this paper is the Decipher score. Could you explain what the score is, what its components are, how it's calculated? Is it DNA, is it RNA, is it both combined? Is it tissue based; is it blood based? Dr. Amar Kishan: Yeah. So, the Decipher is also an approved test now, was approved in 2018. What it is, essentially, and how it's derived is based on the idea originally that patients might have a recurrence after surgery for prostate cancer. And it's just a PSA recurrence. It's this way. It's literally what we call a biochemical recurrence. That patient might not have any problems, whereas other patients with a recurrence might go on to develop metastatic disease. And we didn't have a good way of determining which patient is which. Get back to that prognostic problem that we have. So, some investigators, they looked at men that had radical prostatectomy from 1987 to 2001 at the Mayo Clinic that had archived tissue. They looked at FFPE, or basically paraffin embedded tissue. They extracted the RNA and then did a microarray analysis and looked at transcriptomic signatures and wanted to see, could this discern the patients who had mets, who had clinically significant recurrences from those that didn't? And out of that exercise came the Decipher Genomic Classifier, which basically is based on 22 genes. These are involved with cell proliferation, etc., but it's an RNA-based, tissue-based assay. So, if you wanted to order a Decipher on somebody, you would need to use a biopsy or prostatectomy specimen to do so. Essentially, that the samples, they would take the highest grade, highest Gleason grade specimen, send it to their lab. Their main lab is in California. The company is called Veracyte. And then they will do this RNA express analysis with a microarray and then return a score. The score is 0 to 1. Basically, 0 is the lowest, one is the highest, and it is a way of prognosticating the risk of metastasis. Originally, when you get a Decipher report, it actually will tell you the 5 and 10-year risks of distant metastasis, and we'll quantify that. Dr. Rafeh Naqash: And you said this is approved or has been approved in 2018. So, is this insurance reimbursable at this point? Dr. Amar Kishan: Most insurances do, not all, and the criteria for getting it can vary, so we can talk about it, but it was initially developed in this post-op setting. On the basis of a significant amount of validation studies, it has been moved to being used in the upfront setting as well. So, if you look at some of the ongoing NRG trials, for instance, they are stratifying patients based off the upfront Decipher score. And this is based off of validation studies that have been conducted looking at past RTOG trials and other trials. That said, sometimes it is not approved by commercial insurances in the upfront setting, because that wasn't where it was initially validated and derived. But honestly, here in 2024, that's very uncommon. It's much more common that it's approved. Dr. Rafeh Naqash: Understood. And in your practice, or the medical oncologist practice at your institution or other institutions, is this something that is commonly used for some sort of treatment decision making that you've seen? Dr. Amar Kishan: Yeah. So, as a radiation oncologist, I do think it's a useful test, because my approach is, if we're talking about adding hormone therapy, for instance, which is oftentimes dominating the conversation, we know that it offers a relative benefit to a lot of patients. We've published on this; others have published on it. Let's say it reduces the chance of metastasis by about 40%. 10-year risk of metastasis has a ratio of 0.6. So, 40% reduction. But if your risk of metastasis is 2%, that benefit is not that much in absolute terms. And we don't historically have a great way of saying, what is your absolute risk of metastasis? And I think Decipher is one tool that does tell us that - it literally gives it on the report. Now, is that a holy grail? Is it 100% accurate? Nothing is 100% accurate. But it does give us some quantification. Then I can go back to the patient and say, yes, you will get a benefit from adding hormone therapy, but you're talking about going from 2% to 1%, and so they can decide if that's worth it to them. Conversely, it could be a situation where they really don't want hormone therapy, but it comes back that their risk of metastasis is 20%, and then there's actually a big absolute benefit. So that's how I use it as a radiation oncologist, and we would use it upfront. Now surgeons, and if I was consulting on a post operative patient, maybe it plays more of a role. And do we need to do post operative radiotherapy on this patient, or do we need to add hormone therapy in the postoperative situation? From the medical oncology perspective, there are emerging data that may be useful in the choice of systemic therapy for metastatic disease, but that is a little bit earlier in the investigational stage, I would say. So, when I'm working with medical oncologists, it's often still in this localized setting, and typically, do we add hormone therapy or not, and that type of thing. Dr. Rafeh Naqash: Understood. And from a reporting standpoint, so the Decipher score, I'm guessing it's some sort of a report that comes back to the ordering physician and you basically see the score, it gives you a potential recurrence free survival percentage or a metastasis percentage of what is your risk for having metastasis in the next five years - is that how they generally do it? Because I've personally never seen one, so I'm just curious. Dr. Amar Kishan: Yeah, essentially, it comes back with a score, a numerical score, again, from 0 to 1, and it will basically give you the five-year risk of distant metastasis. The ten-year risk of distant metastasis. You can request an extended report that provides additional, not as well supported signatures that are out there, like ADT response signature, etc. But those maybe may have been published, but are not clinically validated as much, but the actual Decipher report, which goes to patients too, just has this kind of 5,10-year risk of distant metastasis. They have some estimations on prostate cancer specific mortality as well. Dr. Rafeh Naqash: Sure. Now, the third part of this project, and correct me if I'm wrong, the grid database of the 265 genomic signature score. From what I understood, this is a different component than the Decipher score. Is that a fair statement? Dr. Amar Kishan: Yeah. No, that's exactly correct. And that was an exploratory part of this analysis, to be honest. Basically, I think our main focus in the paper was those advances that we've talked about PSMA and Decipher, those happened concurrently. People started developing PSMA PET, people started developing Decipher. And so, what we wanted to understand was, if you have a patient that has extra prosthetic disease on PSMA PET, are those biologically more aggressive cancers, is their Decipher score going to be higher? What can we learn about the biology of this? And we were the first, to my knowledge, where we actually had a large data set of patients that actually received PSMA PETs and Decipher. And that's kind of the gist of the paper. We have patients in the upfront setting, patients in the post radical prostatectomy setting, and we're essentially showing that there is this correlation. In the upfront setting, the odds of extra prosthetic disease are higher for higher Decipher scores, which is kind of maybe validating that this biology is capturing something that's akin to this ability to spread. And in the post-op setting, because we have time to failure, technically, we can calculate a hazard ratio rather than odds ratio. So, we have a hazard ratio that's significantly associated with an increased risk of spread for patients with higher Decipher. The grid portion, which is the genomic resource information database, was more of an exploratory part where I mentioned the Decipher score is based off this microarray, they're looking at 1.4 million transcripts. Only 22 are part of the Decipher, but you can request the rest of the signature data as well. And so, we wanted to look at other pathways, other signatures that have been published, like looking at DNA repair, neuroendocrine pathway, just to see if we could see any correlations there that's not necessarily as clinically actionable. These are more exploratory. But again, we were trying to just look at whether patients who had non localized disease on their PSMA PET, whether their primary had more aggressive biology. We did see that. So that's kind of loosely speaking things like PTEN loss, androgen receptor, DNA repair, metabolism, neuroendocrine signaling, which are thought to be portenders of aggressive disease. Those pathways were upregulated at the RNA level in patients who had non-localized disease. And that's kind of the take home from that. But I wouldn't say any of that is clinically actionable at this point. It's more kind of defining biology. Dr. Rafeh Naqash: Some of the interesting correlations that you make here, at least in the figures that we see, you're looking at different local occurrences, nodal metastases, M1A and M1B disease. And one thing that I'm a little curious about is the Decipher score seems to be lower in pelvic nodal metastasis, that is, PSMA PET positive versus local recurrence, which has a slightly higher Decipher score. Is that just because of a sample size difference, or is there a biologically different explanation for that? Dr. Amar Kishan: Yeah, that's a good point. I would assume that's probably because of a sample size in this case, and it's a little bit complicated. It wasn't statistically different. And it was 0.76 on average for patients with local recurrence and 0.7 for patients with a pelvic nodal metastasis. Well, what I think is interesting is we can maybe think that in this post-op setting the time to failure could have been long in some of these cases. So, it is conceivable that an isolated nodal recurrence 10 years after the surgery, for instance, is not as aggressive a cancer as a local recurrence in a short time after the surgery. And that's not taken into account when you're just looking at median scores like we are in this fox and whiskers plot. But overall, I think what it's suggesting is that there are patients who have more indolent disease. That's actually pretty widespread there. There are pretty indolent cases that have these nodal metastases. So just because you have a nodal metastasis doesn't mean it's an incredibly aggressive cancer, biologically. Dr. Rafeh Naqash: Now, the exploratory component, as you mentioned, is the grid part where you do look at TP53, which is a cell cycle gene, and higher TP53 associated with worse recurrences, from what I understand. Do you see that just from a cell cycle standpoint? Because from what I, again, see in the paper, there's a couple of other cell cycle related signatures that you're using. Is that just a surrogate for potential Gleason score? Have you guys done any correlations where higher Gleason score is associated with maybe higher cell cycle checkpoint, pathway related alterations and replication stress and DNA damage and perhaps more aggressive cancers? Dr. Amar Kishan: Yeah, that's a great question. We haven't done that in this paper, but it has been published before that there is this correlation loosely between grade and some of these parameters - so repair, metabolism, androgen receptor signaling. However, it's a very great point that you bring up, which is that it's pretty heterogeneous and that's why we need something like this as opposed to Gleason score. So, you can have Gleason 10 cancer. I mean, that would be pretty uncommon. But within the Gleason 9, at least, which we have published on and looked at, there's a heterogeneity. There are some that are biologically not that aggressive. And the converse Gleason 7, you can have some that are actually biologically aggressive. That's why it may be useful to move away from just the pathological architecture and get a little bit more into some of these pathways. Dr. Rafeh Naqash: What's the next step here? I know this perhaps isn't ready for primetime. How would you try to emphasize the message in a way that makes it interesting and clinically applicable for your colleagues in the GU community? Dr. Amar Kishan: Yeah. I think for me, what I would try to emphasize here and what I think is the main takeaway is this is kind of a validation that having extra prostatic disease on PSMA PET is likely suggestive of a more aggressive disease biology. And I think what this stresses to me is the importance of getting a PSMA PET, particularly in patients with high-risk prostate cancer. This isn't always happening. And I think if we see things on a PSMA PET, we really need to consider systemic therapy intensification. And what do I mean by that as a practical point? You have a high-risk prostate cancer patient. You get a PSMA PET, you see an isolated pelvic lymph node. If we believe the results of the study, that's a more aggressive biology likely. Whether we have the Decipher or whether we have genomic signatures, which we may or may not have, maybe that patient should get treated with something like an androgen receptor signaling inhibitor in addition to ADT, more akin to a clinically node positive case. So, intensify the systemic therapy, more aggressive disease. That's how I would incorporate it practically into my practice, that really what we're seeing on the PSMA PET is real. It's a reflection of biology that's aggressive. It's not just some Will Rogers effect where you're upstaging stuff needlessly. I think this is telling us some true biology. So that's kind of what my takeaway would be. I think future areas of investigation would be, honestly, to try to have a better idea of what's going on in these metastases. So, if you could design a study potentially, where your biopsy some of these and actually do sequencing and understand a little bit more of that. And so, we're looking into stuff like that. But my takeaway for like the everyday clinician would be to try to get a PSMA PET, if you can, and to intensify therapy on the basis of that, or at least consider it, discuss it in a multidisciplinary setting. Dr. Rafeh Naqash: And I'm guessing somebody out there, perhaps even you, are thinking or planning on doing a ctDNA MRD based correlation here, since that's up and coming in this space. Dr. Amar Kishan: That is up and coming, I think one of the challenges in prostate cancer is the amount of ctDNA can be low. But yes, you're right, that's certainly things that a lot of us are looking at, too. Dr. Rafeh Naqash: Excellent. Well, thank you for the science discussion, Dr. Kishan, could you tell us a little bit about yourself, your career trajectory, where you started, what you're doing, and perhaps some advice for early career junior investigators, trainees, things that might have worked for you, that could also work for them as they are progressing in their careers. Dr. Amar Kishan: Sure. So, yeah, I'm a radiation oncologist at UCLA. I run the prostate cancer radiation program. Clinically. I'm also heavily involved in our research enterprise, so I kind of oversee the clinical and translational research aspect. That's what I do currently. So, I did my residency in radiation oncology at UCLA. Just on a personal note, my wife is from LA, her parents live in LA. We really wanted to stay in LA, so I was fortunate to be able to join the faculty here. I always liked GU oncology, so that was kind of a natural thing for me to kind of go into this position here and try to build the GU program. I've been very fortunate to have great collaborators. My message to students and trainees is to try to reach outside your department for mentorship as well. It's important to have people inside your department who can mentor you. But as a radiation oncologist, I work so closely with urology, so closely with medical oncology that I'm very fortunate to have individuals in those departments who have a vested interest in me and my success as well. I like working with them. It's important to be a team player. If they need help, you help them. If you need help, you ask for help from them. So, I think that's the single biggest thing that I would say to any trainee is don't be intimidated. Please reach outside of your department. Lots of people are willing to help and provide mentorship, and it's helpful to have that perspective. We are in a very multidisciplinary environment and era of practicing medicine. Dr. Rafeh Naqash: Well, thank you again for those personal insights and especially for submitting your work to JCO PO. And we hope to see more of this work perhaps in the subsequent sessions for JCO PO, and maybe we'll bring you back again. And at that point, the Decipher and the PSMA PET scan will have more data, more implementation in the clinically relevant real-world setting. Dr. Amar Kishan: Thank you very much. And if I could just give one quick shout out. The first author of this work, which I presented, was Dr. John Nikitas, who is a trainee that works with me here at UCLA a PGY5 resident. So, I do want to give credit to him as well. Dr. Rafeh Naqash: And John, if you're listening to this hopefully, it's always great to get a shout out from your mentor. Thank you both again for putting in the work and effort to submit this manuscript. Thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcasts.   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.    Disclosures  Dr. Kishan Honoraria Company: Varian Medical Systems, Boston Scientific,  Janssen Oncology  Consulting or Advisory Role Company: Janssen, Boston Scientific, Lantheus  Research Funding Company: Janssen , Point Biopharma

JCO PO author Dr. Alok A. Khorana, MD, FASCO, Professor of Medicine, Cleveland Clinic and Case Comprehensive Cancer Center, shares insights into the JCO PO article, “Molecular Differences With Therapeutic Implications in Early-Onset Compared With Average-Onset Biliary Tract Cancers.” Host Dr. Rafeh Naqash and Dr. Khorana discuss how multiomic analysis shows higher FGFR2 fusions and immunotherapy marker variations in early-onset biliary cancer. TRANSCRIPT Dr. Rafeh Naqash: Hello, and welcome to JCO Precision Oncology Conversations, where we bring you engaging conversations with authors of clinically relevant and highly significant JCO POarticles. I'm your host, Dr. Rafeh Naqash, Podcast Editor for JCO Precision Oncology and Assistant Professor at the OU Health Stephenson Cancer Center at the University of Oklahoma.  Today, we are joined by Dr. Alok A. Khorana, Professor of Medicine at the Cleveland Clinic and Case Comprehensive Cancer Center, and also the Senior Author of the JCO Precision Oncology article titled, “Molecular Differences With Therapeutic Implications in Early-Onset Compared With Average-Onset Biliary Tract Cancers.”  At the time of this recording, our guest disclosures will be linked in the transcript.  Dr. Khorana, it's an absolute pleasure to have you here today, and welcome to the podcast. Dr. Alok A. Khorana: Thank you. It's an absolute pleasure to be here and thank you for highlighting this article. Dr. Rafeh Naqash: Absolutely. We're going to talk about science, obviously, and a few other things. So to start off, for the sake of our audience, which comprises academicians and community oncologists as well as trainees, can you tell us a little bit about biliary tract cancers, what we have learned over the last decade or so, where the standard of treatment currently lies. And then we can dive into the article that you published. Dr. Alok A. Khorana: As many of you who treat GI cancers know, biliary tract cancers for a long period of time were sort of the orphan cancer in the GI cancer world. They're not nearly as common as, say, pancreatic cancer, and certainly not as common as colorectal cancer. They're sort of also, in this weird ‘no man's land' between well known sort of adjuvant therapy trials in pancreatic cancer or colorectal cancer, but because they're not as high in volume, there weren't really large trials done in this population. What's really changed in the past decade, especially, has been the slow but sure realization that biliary tract cancers are in fact a target rich cancer, almost similar to what you would see with lung cancer, and that's only a slight exaggeration. And in some studies, as many as up to 40% of patients with biliary tract cancers can have something that's targetable. And that's really revolutionized the way we think of biliary tract cancers. It also separated this field from pancreatic cancer where formerly the two used to be lumped together, and even within biliary tract cancers, we are now slowly realizing that there are differences between intrahepatic, extrahepatic and gallbladder cancers. Big change is really afoot in this field, particularly with the identification of mutation directed targets. Dr. Rafeh Naqash: Thank you for that explanation.  Now, another question I have is, although I don't see any GI cancers, but I have good colleagues of mine at our cancer center who see a lot of GI pancreatic/biliary cancers, and one of the things that comes up in our molecular tumor board often is how certain cancers of unknown primary end up being identified or categorized as biliary tract cancers based on NGS. And again, the uptake for these NGS is perhaps isn't optimal in the field yet, but in your practice, how do you approach situations like that? Do you use NGS in certain cases where the tissue of origin or the patterns of the mutations indicate that this might be biliary tract cancer and then treat the patient accordingly?  Dr. Alok A. Khorana: Yeah, that's true. And that's certainly how I approach things, and I would say even in my own personal practice, that has been a change. I was a little bit skeptical about the benefit of sort of tissue of origin type of testing in carcinoma of unknown, primarily, especially if you can sort of narrow it down to one or other area of the GI tract. But with the identification of sort of targeted subpopulations, especially of biliary tract cancer, I think it's become imperative. And I know we're going to get into the paper, but if you want to learn nothing else from this 20, 25 minute podcast, one lesson I just want to make sure everybody gets is that any patient with biliary tract cancer should have NGS done as soon as possible. Dr. Rafeh Naqash: Thank you for highlighting that important aspect.  Now, going to the topic at hand, what was the driving factor? I've heard a lot about colorectal cancers, early onset versus later onset. What was the reason that you looked at biliary tract cancers? Is that something that you've seen on a rise as far as early onset biliary tract cancers is concerned?  Dr. Alok A. Khorana: Yeah. So we got into this subject also from starting out at colorectal cancer. And as you know, and I'm sure most of your audience knows, there's been a lot of literature out there over the past five, six, seven years suggesting and then documenting and then sort of proving and reproving that colorectal cancer is on the rise, and especially in people younger than age 50. And even in that population, it's on the rise in two different subpopulations, people in their 20s and 30s and then people in their 40s that are close to the screening colonoscopy rates. That's been investigated heavily. We still don't fully understand why that's happening, but it's not restricted to the United States. It's a worldwide phenomenon. You can see it in the United States, in North America. You can see it in western Europe, but you can also see it in many Asian countries with specific sort of subpopulations. For instance, in some countries, men are more likely to have early onset cancers.   And then a newer finding that sort of emerged over the past couple of years is that this early onset increase in cancers is not just restricted to colorectal cancer, although that's the one that sticks out the most, but in fact, is widespread across a bunch of different types of cancers. In my own research program, we had gotten into a sort of better understanding of early onset colorectal cancer a couple of years ago, driven primarily by the sort of patients that I saw in my practice. And it's just, as you know, when you have a couple of those heartbreaking cases and they're just impossible to forget, and it sort of just drives your attention, and then you want to do something to help them. And if you can't help them personally, then you want to do something that can change the field so that more of these patients are not coming in your clinic next year or the year after.  So a couple years ago, at the Cleveland Clinic where I practice, we created a center for young onset cancers, and at the time it was primarily focused on colorectal cancer. But as we are getting into colorectal cancer, we realize that beyond colorectal cancer, we are also starting to see more younger people with other cancers, including pancreas cancer, including gastric cancer, and including bile duct cancers. And we realized that because so much attention was being focused on colorectal, that maybe we should also be paying a little bit of attention to what was happening in this space. I want to, for your listeners, point out that the problem in bile duct cancers is not to the same degree as you see in colorectal cancer. Just a couple numbers to sort of, to set this in perspective: about 5%, 7% of bile duct cancers are young onset - it's not a huge proportion - 90%+ percent of patients are not young onset. But the impact on society, the impacts on those providing care, is obviously substantial for younger patients. And it is true that even though the proportion of patients is not that high, the incidence is rising.   And there's a very nice study done a couple of years ago and published that looked at what the cancers are that are rising at the highest rates. And bile duct cancer and gallbladder cancers were listed amongst the two with the highest rate, so about an 8% rate per year of increase. And so that's really what drove our interest was, as we're seeing early onset bile duct cancers, it's rising year by year, and what is this disease? Is it the same as you see in sort of the average patient with bile duct cancer? Is it different? How do we characterize it? How do we understand it? What are some of the causes precipitating it? And so that's what led us to sort of one of the investigations that we've documented in this paper.  Dr. Rafeh Naqash: Excellent.   So, talking about this paper, again, can you describe the kind of data that you use to understand the molecular differences and also look at potential immune signatures, etc., differences between the groups? Dr. Alok A. Khorana: Yeah. So the objective in this paper was to look at genomic differences between early onset and usual onset, or average onset biliary tract cancers. And this sort of followed the paradigm that's already been established for early onset colorectal cancer, where you take a bunch of people with early onset disease, a bunch of patients with average onset or usual onset disease, and then look at the profiling of the tumors. And we've done this for genomics, we've done this for microbiomics, we've done it for metabolomics. And the lessons we've learned in colorectal cancer is that, in many ways, the profiles are actually quite substantially different. And you can almost think of them as diseases of the same organ, but caused by different processes, and therefore leading to different genotypes and phenotypes and microbiomes. We had absorbed that lesson from colorectal cancer, and we wanted to replicate it in this type of cancer.  But as we discussed earlier, this is a relatively rare cancer, not that many cases per year. For colorectal, we could do a single institution or two institution studies. But for this, we realized we needed to reach out to a source of data that would have access to large national data sets. We were happy to collaborate with Caris Life Sciences. Caris, many of you might know, is a provider of genomics data, like many other companies, and they house this data, and they had the age categorization of patients less than 50, more than 50. And so we collaborated with investigators at Caris to look at all the specimens that had come in of bile duct cancers, identified some that were young onset and some that were older onset. It was roughly about 450 patients with the early onset or young onset, and about 5000 patients with usual onset cases. And then we looked at the genomics profiling of these patients. We looked at NGS, whole exome sequencing, whole transcriptome sequencing, and some immunohistochemistry for usual, like PDL-1 and MSI High and things like that. And the purpose was to say, are there differences in molecular profiling of the younger patient versus the older patient? And the short answer is yes, we did find substantial differences, and very crucial for providers treating these patients is that we found a much higher prevalence of FGFR2 fusion. And that's important because, as I'm sure you've heard, there's a ton of new drugs coming out that are targeting specifically FGFR fusion in this and other populations. And hence my statement at the outset saying you've got to get NGS on everybody, because especially younger patients seem to have higher rates of some of these mutations.  Dr. Rafeh Naqash: Excellent. You also looked at the transcriptome, and from what I recollect, you identified that later onset tumors had perhaps more immune favorable tumor microenvironment than the early onset. But on the contrary, you did find that FGFR2 early onset had better survival. So how do you connect the two? Is there an FGFR link, or is there an immune signature link within the FGFR cohort for early onset that could explain the differences? Dr. Alok A. Khorana: Yeah, that's a great question. So, to kind of summarize a couple of these things you talked about. So, one is we looked at these genomic alterations, and, yes, FGFR2 fusion was much more prevalent. It's close to 16% of young onset patients, as opposed to roughly 6% of average onset patients. So almost a threefold increase in FGFR fusion. And because there's so many drugs that are targeting FGFR fusion, and because the population included a period of time when these drugs had already been approved, we think some of the benefit or the improvement in median survival associated with being younger is likely driven by having more FGFR fusion and therefore having more drugs available to treat FGFR fusion related tract cancer with corresponding increase and increase in survival. And that was part of it. There was one other alteration, NIPBL fusion, that's been sort of known to be associated with a certain subtype of cholangiocarcinoma, but it doesn't really have a drug that targets it, so it's not sort of very useful from a clinical perspective.   The other two things you talked about, so transcriptome and immuno oncology markers, we found a couple different results on this. So one is that we found in younger people, angiogenesis was enriched, and why this is so we don't quite have a good answer for that. The other was inflammatory responses. So there's a couple of gamma interferon pathways and a couple other types of pathways that you can sort of do pathway analysis, and we found that those were enriched in the older patients or the average onset patients. But the benefit for immunotherapy was similar across the two groups. So even though we saw these differences in signaling in terms of which pathways are upregulated or downregulated, it didn't seem to translate into the current generation of immune checkpoint inhibitors that we're using in terms of benefit for patients. But we did see those differences.  Dr. Rafeh Naqash: I completely agree, Doctor Khorana. As you mentioned, that one size fits all approach does not necessarily work towards a better, optimal, personalized treatment stratification. So, as we do more and more sequencing and testing for individuals, whether it's early onset cancers or later onset cancers, figuring out what is enriched and which subtype, I think, makes the most sense.   Now, going to the FGFR2 story, as you and most listeners probably already know, FGFR is an approved target, and there are a band of FGFR inhibitors, and there's some interest towards developing specific FGFR2, 3 fusion inhibitors. What has your experience with FGFR inhibitors in the clinic been so far? And what are you personally excited about from an FGFR standpoint, in the drug development space for GI cancers?  Dr. Alok A. Khorana: Yeah, I think the whole FGFR fusion story sort of actually deserves more excitement than it's gotten, and it may be because, as I mentioned earlier, biliary tract cancers are a relatively low volume type of cancer. But the results that we are seeing in the clinic are very impressive. And the results that we are anticipating, based on some ongoing phase two and phase three trials, appear to be even more impressive for the very specific inhibitors that are about to hopefully come out soon.   Also, the possibility of using successive lines of FGFR inhibitors - if one fails, you try a second one; if the second one fails, you try a third one because the mechanisms are subtly different - I think it will take a little while to figure out the exact sequencing and also the sort of the rates of response in people who might previously have been exposed to an FGFR inhibitor. So that data may not be readily available, because right now most patients are going in for longer trials. But having that type of possibility, I think, kind of reminds me of the excitement around CML back when imatinib suddenly became not the only drug and a bunch of other drugs came out, and it's kind of like that. I think again, it's not a very common cancer, but it's really wonderful to see so many options and more options along the way for our patients. Dr. Rafeh Naqash: Thank you. Now, going to your personal story, which is the second part of this conversation, which I think personally, for me, is always very exciting when I try to ask people about their personal journeys. For the sake of the listeners, I can say that when I was a trainee, I used to hear about Dr. Khorana's course, I always thought that Dr. Alok Khorana was a hematologist. My friends corrected me a few years back and said that you're a GI oncologist. Can you tell us about your love for GI oncology and the intersection with hematology thrombosis, which you have had a successful career in also? Can you explain how that came about a little bit? Dr. Alok A. Khorana: Yeah, sure. So it is a common, I guess I shouldn't say misperception, but it's certainly a common perception that I'm a hematologist. But I'll sort of state for the record that I never boarded in hematology. I did do a combined hem-onc fellowship, but only boarded in oncology. So I'm actually not even boarded in hematology. My interest in thrombosis came about- it's one of those things that sort of happen when you're starting out in your career, and things align together in ways that you don't sort of fully understand at the time. And then suddenly, 10 years later, you have sort of a career in this.   But it actually came about because of the intersection of, at the time, angiogenesis and coagulation. And this is the late ‘90s, early two ‘00s, there was a lot of buzz around the fact that many of the factors that are important for coagulation are also pro angiogenic and many factors that are coagulation inhibitors. These are naturally occurring molecules in your body, and can be anticoagulant and anti angiogenic. A great example of this is tissue factor, which is, as you'll remember from the coagulation pathways, the number one molecule that starts off the whole process. But less widely appreciated is the fact that nearly every malignancy expresses tissue factor on its cell surface. This includes breast cancer, it includes leukemia cells, it includes pancreatic cancer. In some cancers, like pancreatic cancer, we've even shown that you can detect it in the blood circulation. And so for me, as a GI oncologist who was seeing a lot of patients get blood clots, it was particularly fascinating to sort of see this intersection and try and understand what is this interaction between the coagulation and angiogenic cascades that's so vital for cancers. Why is coagulation always upregulated in cancer patients? Not all of them get blood clots, but subclinical activation of coagulation always exists. So I would say I was fascinated by it as an intellectual question and really approached it from an oncology perspective and not a hematology perspective.   But then as I got deeper into it, I realized not everybody's getting blood clots, and how can I better predict which patients will get blood clots. And so I had both a hematology mentor, Charlie Francis, and an oncology mentor, Gary Lyman. And using sort of both their expertise, I drafted a K23 career development award specifically to identify predictors of blood clots in cancer patients. And that's the multivariate model that later became known as the Khorana Score. So again, I approach it from an oncology perspective, not a hematology perspective, but really a fascinating and still, I would say an understudied subject is why are cancer patients having so many clotting problems? And what does it say about the way cancer develops biologically that requires activation of the coagulation system across all of these different cancers? And I think we still don't fully understand the breadth of that. Dr. Rafeh Naqash: Very intriguing how you connected two and two and made it a unique success story. And I completely agree with you on the tissue factor. Now there's ADCs antibody drug conjugates that target tissue factor, both a prude as well as upcoming.   Now, the second part of my question is on your personal journey, and I know you've talked about it on social media previously, at least I've seen it on social media, about your interactions with your uncle, Dr. Har Gobind Khorana, who was a Nobel Prize winner in medicine and physiology for his work on DNA. Could you tell us about how that perhaps shaped some of your personal journey and then how you continued, and then also some personal advice for junior faculty trainees as they proceed towards a successful career of their own? Dr. Alok A. Khorana: Yeah, thank you for bringing that up. So very briefly, this is about my uncle. He's actually my great uncle. So he's my grandfather's youngest brother. And I grew up in India in the ‘70s and ‘80s, and at the time, I ran away from this association as fast as I could, because growing up in India in the 70s and ‘80s, it was a socialist economy. There wasn't a lot going on. There was certainly none of the IT industry and all of everything that you see right now. And so there were very few icons, and my great uncle was definitely one of those few icons. As soon as you mentioned your last name, that would sort of be the first question people would ask. But he did serve as a role model, I think, both to my father, who was also a physician scientist and a professor of medicine, and then to myself in sort of making me realize, one, that you can't really separate medicine from science. I think those are really integrated, and we want to ask questions and answer questions in a scientific manner. He chose to do it in a basic science world. My father did it in a clinical science world, and I have done it in a clinical and a translational science world. Again, sort of using science as the underpinning for sort of understanding diseases, I think, is key. And so that was certainly a massive inspiration to me.  And then after I immigrated to the US in the late ‘90s, I met him on a regular basis. He was certainly very inspirational in his successes, and I realized the breadth of what he had done, which I did not realize in my youth growing up. But this is a person who came to the US. This was before Asian immigration was even legal. So he got here and they had to pass a special bill in Congress to let him be a citizen that was based on the sort of work that he had done in Canada and in the UK before he came here. And then he sets up shop in the University of Wisconsin in Madison and hires tons of these postdocs and essentially converted his lab into this massive factory, trying to figure out the genetic code. Really just the type of dedication that that needs and the amount of work that that needs and the ability to do that in a setting far removed from where he grew up, I think it's just really quite mind boggling.  And then he didn't stop there. He got the Nobel for that, but I have these letters that he wrote after he got the Nobel Prize, and he was just completely obsessed with the possibility that getting the Nobel would make him sort of lose his mojo and he wouldn't be as focused on the next aspects of science. And he was just really dedicated to synthesizing DNA in the lab, so creating artificial DNA, which he ended up doing. And the offshoot of that work, so not just the genetic code, but PCR essentially was developed by his lab before it became sort of what we now know as PCR. And then ditches all of that in the ‘80s and ‘90s and moves to understanding the retina and just focuses on retinal disorders. And then signal transduction, essentially trying to figure out when a single photon of light hits your eye, what happens biologically. It's a completely different field. And just took that on and spent the next 20,30 years of his life doing that. So the ability to sort of change fields, I thought that was very inspirational as well, that you don't have to just stick to one question. You can get into one question, answer it as much as possible, and then find something else that's really interesting to you and that really grabs your attention, and then stick with that for the next couple of decades. So lots to learn there. Dr. Rafeh Naqash: Thank you. Thank you. And then, based on some of your personal lessons, what's your advice for junior faculty and trainees as you've progressed in your career?  Dr. Alok A. Khorana: I think, number one, and I can't emphasize this enough, and sometimes it actually causes a little bit of anxiety, but it is finding the right mentor. And for me, certainly that was key, because my mentor, who was Charlie Francis, was not an oncologist who was a hematologist, but was like me, sort of supported this idea of trying to understand, hey, why does coagulation interact with cancer? And so he approached it from a hematology perspective, I approached it from a cancer perspective, but he sort of gave me the freedom to ask those questions in his lab and then later on in the clinical setting and clinical translational setting, and then got me access to other people who are experts in the field and introducing you and then getting you on committees and making sure you sort of get into clinical trials and so on. And so having a mentor who sort of supports you but doesn't stifle you, and that's really key because you don't want to just ask the question that the mentor is interested in. And as a mentor now, I don't want to have my mentee ask the question that I'm interested in, but also a question that the mentee is interested in. And so there's a little bit of a chemistry there that's not always replicable, and it can go wrong in sort of five different ways, but when it goes right, it's really vital. And I mentioned it causes anxiety because, of course, not every day is great with your mentor or with your mentee, but over a period of time, has this person done sort of their best to get your career off to a start? And have you served that mentor well by doing the things that are– there's responsibilities on both sides, on both on the mentor and on the mentee. And if you can find that relationship where there's a little bit of chemistry there and both of you are effectively discharging both your responsibilities and satisfying your intellectual curiosity, I think that can't be beat, honestly. To me, sort of number one is that and everything else follows from that. So, the networking, making sure your time is sort of allocated appropriately, fighting with sort of the higher ups to make sure that you're not having to do too much, things that are sort of away from your research interests, all of that sort of flows from having the right person. Dr. Rafeh Naqash: Couldn't agree with you more, Dr. Khorana, thank you so much. It was an absolute pleasure. Thank you for sharing with us the science, the personal as well as the professional journey that you had. And hopefully, when you have the next Khorana Score, Khorana score 2.0, JCO Precision Oncology will become the home for that paper and we'll try to have you again maybe in the near future.  Thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcast. Thank you so much.   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.   Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.   Disclosures: Dr. Khorana  - Honoraria Company: Pfizer, Bayer,  Anthos, Sanofi, BMS, WebMD/MedscapeConsulting or Advisory Role Company: Janssen, Bayer, Anthos, Pfizer, Sanofi, BMS Research Funding Company: Anthos, Bristol-Myers,  Squibb Travel, Accommodations, Expenses Company: Janssen, Bayer, Bristol-Myers Squibb 

Host Dr. Davide Soldato interviews Dr. Sana Raoof to discuss the JCO article Turning the Knobs on Screening Liquid Biopsies for High-Risk Populations: Potential for Dialing Down Invasive Procedures. TRANSCRIPT Dr. Davide Soldato: Hello, and welcome to JCO After Hours, the podcast where we sit down with others from some of the latest articles published in the Journal of Clinical Oncology. I am your host, Dr. Davide Soldato, Medical Oncologist at Ospedale San Martino in Genoa, Italy. Today, we are joined by JCO author Dr. Sana Raoof, Physician at Memorial Sloan Kettering, to talk about her article, “Turning the Knobs on Screening Liquid Biopsies for High-Risk Populations: Potential for Dialing Down Invasive Procedures.”   Thank you for joining us today, Dr. Raoof. Dr. Sana Raoof: Thank you so much. It's lovely to be here. Dr. Davide Soldato: So, Dr. Raoof, I just wanted to start a little bit about the theme of your article, which is really centered around multi-cancer early detection tests. And this comes from the results of several studies that showed their reliability and efficacy in identifying cancer in the average risk population. But I just wanted to ask you if you could give us and our readers a brief overview of how these tests work and how they were designed for this specific population. Dr. Sana Raoof: Of course. Well, there's an interesting story. The origin of multi-cancer early detection tests actually begins with insights that come from the field of obstetrics and gynecology. So about six or seven years ago, in the peripheral blood of pregnant women, we discovered that you can actually find fetal DNA floating around. And that was an early discovery of cell free DNA coming from the baby into the mother's bloodstream. But in some of those young, otherwise healthy women, we also discovered that there's another clonal signal, unfortunately not coming from the fetus, but coming from an undiagnosed tumor. And that led to the entire field of circulating tumor DNA and all of its applications.  Of course, scientists in the last six or seven years have harnessed the fact that DNA and the methylation patterns on the circulating tumor DNA, as well as other analytes like glycosaminoglycans, proteins, and other analytes, are secreted by tumors into the peripheral blood in order to try and screen for tumors, hopefully at early stages, when there are still curative, definitive interventions that are available. There's several different tests now that are providing the ability to detect cancers at many stages, including early stages. They're in different phases of preclinical to clinical development, and one is even commercialized and available by prescription in the United States. Dr. Davide Soldato: Okay. So I think that in most of these tests, they really look at the tumor DNA, so they identify mutations or, for example, methylation patterns. But do we also have some tests that integrate some other type of biomarkers that we can identify in the blood? Like, are they integrated all with the others, or are we just relying on circulating tumor DNA? Dr. Sana Raoof: It's a great question. There's a lot of really fascinating biology that different companies predominantly are using in order to find signs of early cancer. One of the analytes that I find really interesting, other than looking for small variants in circulating tumor DNA and looking at methylation patterns, as you mentioned, is looking at fragment length. So, for example, the company DELFI looks at the different patterns of the length of DNA fragments that are floating around in the peripheral blood. And not only is fragment length tissue specific, so in theory, a fragmentomics based multi-cancer early detection test could tell us what is the tissue that this aberrant signal is coming from, but they can also tell you if there's likely a cancer present, because there's a difference in fragment length patterns in cancer versus non cancer.  There are also other analytes. I mentioned glycosaminoglycan. There's another company that doesn't yet have prospective data, to my knowledge, that is making a test that looks at these analytes instead. There are other companies, again, without prospective data yet, that are looking at circulating tumor cells. And I'm sure that in the next few years, we're going to start getting prospective data from all of these players and also hear about other analytes that scientists have found can predict cancer from non cancer and maybe even protect tissue of origin based on artificial intelligence. Dr. Davide Soldato: So you mentioned artificial intelligence. So, basically what you're suggesting, but correct me if I'm wrong, is that when we use this test, we are actually measuring something in the bloodstream, but at the same time, we are actually applying some type of artificial intelligence to actually interpret these results and then give us the definitive results, or what we would call like a positive and a negative of the tests, is that right? Dr. Sana Raoof: Yeah, absolutely. And it's an important distinction that you're making, we are measuring something in the blood, but we're not just measuring it. We're using machine learning algorithms that have been trained on thousands and thousands of patients with cancer and thousands and thousands of patients without cancer, and have measured various analytes and analyzed the patterns, for example, of DNA sequence, or bisulfite sequencing of methylation patterns of patients with and without cancer, and have been trained to look for the differences between them. And so the analyte that we're looking for is not a specific mutation per se, but is a pattern that looks like patterns that you typically find more so in cancer patients.   There's many different companies, they are trained on different types of cancer. So some companies, like GRAIL, have a test that looks for a very expanded list of over 50 cancer types. Other tests have a narrower focus and were trained and validated on a smaller list of cancer types. So there's just a great diversity in this space. These tests are trained to look for different types of cancer. They're trained and validated on different populations of interest. So, for example, some of the populations that these tests were trained on are predominantly white, and that will have impacts, potentially on how these tests perform in non-white populations. And that's a really interesting area of future research. These tests may or may not have included cancer survivors in their populations, and that could ultimately impact how these tests perform in those populations.  So there's just so much to learn, so much data that's going to be coming out in the next few years from all of these different key players in the multi-cancer early detection space. But one thing that I'm sure of is between all of the different analytes, all of the different training and validation studies, and all of the different prospective studies, we're going to learn a tremendous amount about the potential clinical utility of using multi-cancer early detection tests to complement the few standard of care surveillance cancer screening tests that we have recommended today. Dr. Davide Soldato: So just taking a step back and going back to the fact that we actually use machine learning algorithms to identify a pattern that can give us an idea of whether cancer is present or not, I believe that there is also some room for calibration of these types of tests. And I think that this is one of the key arguments that you make in your paper where you say that we can actually personalize a little bit more these types of tests to understand and then to decide what we are looking for. Is that correct and can you expand a little bit on that? Dr.Sana Raoof: Yeah, absolutely. This is the central concept of the paper that we're discussing. Because these tests are machine learning based, as I said, they're trained to say cancer versus not cancer, and some of them are further trained to say, coming from this organ or coming from that organ. But what does it mean to say cancer or not cancer? There are specific thresholds that are defined to say, above this threshold of signal detection, we're going to say this is a positive cancer signal detected, and below it we're going to say negative. And so right now, these tests are kind of designed to have this binary output, and the concept that I wanted to put forth in the paper is it doesn't necessarily have to be binary, and the thresholds don't have to be static. So, for example, you can imagine that in an average risk population where the pretest probability of cancer in your lifetime for Americans, it's pretty high, roughly 40% for lifetime. But at any given moment in time when you're getting a test, it's lower. For example, in Americans, 50 to 80, the chance of having cancer at any given moment is just under 3%. So you don't necessarily want a test that is very nonspecific, you don't necessarily want to tell a lot of perfectly healthy people that are asymptomatic screening populations that they have cancer if they don't. And so these tests were designed to have very high specificity, predominantly across the board, across the different companies making them at the cost of, in some cases, having lower or moderate sensitivity in early stages.   And it's important to keep in the back of your mind that we cannot ever expect the types of early stage sensitivities from multi-cancer early detection tests that we're used to thinking about for single cancer screens that are just optimized for one single organ. They work in a completely different way. So I don't expect a future where the sensitivity of a mammogram, which is only for breast cancer, is going to be analogous to the sensitivity of a blood-based test that's looking for all cancers in your entire body. I don't think it's fair to expect that. But I do think it's possible to imagine a future where we do change the thresholding of these tests that were trained and validated in average risk screening populations, and say, “Let's turn the knob on the dial and let's take the sensitivity a little bit higher, even if it means the specificity drops from 99%, for example, which is the very high number of the gallery test, down to 98%, down to 97%. Let's see how this affects the positive predictive value and the negative predictive value of the test.” And how having a higher negative predictive value by having a higher sensitivity may or may not make it more clinically useful for higher risk populations that have higher pretest probabilities, in which case we are kind of more interested in being sure that we're ruling out cancer.  Another concept that I talk about in the paper, aside from just turning the knobs, is to make it a continuous variable rather than a binary report. Rather than saying signal detected or not signal detected, I can also imagine a future where we personalize the output of multi-cancer early detection tests to return a score, for example, from 1 to 100 or 1 to 10, and give physicians the ability to use that continuous variable in addition with other clinical findings, physical exam findings, other labs, symptoms, patient's past medical history, family history, all of that together to make decisions about should we pursue further workup, should we do an invasive biopsy. This is kind of the way that we use other scoring tests in oncology, like the oncotype tests for breast cancer, decipher test in prostate cancer. And I think physicians like having continuous variables to work with and to help them make very personal decisions for patients' diagnostic workups. Dr. Davide Soldato: To summarize a little bit, what you're arguing in the paper is that we could potentially modify a little bit these tests as they fit the type of population that we are looking for. For example, if we are looking at the average risk person in America, there we just want to be sure that we are just doing additional workout and additional follow ups and additional invasive procedure, for example, biopsy, when we have a very high probability of finding that cancer. At the same time, if we have someone who has a baseline risk which is higher, like cancer survivors, in that case, we are more interested in seeing if there is really cancer at that point, and so we can increase the sensitivity and go down on specificity, but still looking at the overall outcome that we want to have for that specific patient.  One thing that I was wondering is, do you also see a future where we personalize a little bit more also including additional information that comes from risk factors, environmental or behavioral patterns, type of diet, or these types of risk factors that we already know from epidemiology are associated with a higher risk? So could we potentially customize this test even more, saying, this patient has a higher risk of developing colorectal cancer, so could we look more specifically to that specific cancer type and that specific risk compared to tobacco associated cancers, that for that specific patient, they are not so relevant?  Dr. Sana Raoof: What you're saying is actually a fascinating and really compelling idea, and it reminds me of the way that noninvasive prenatal testing works. So, again, back to the world of obstetrics and gynecology, you have a woman at the end of her first trimester having fetal DNA testing to look for chromosomal abnormalities. And when you order that test, you actually do put in various features about the woman to help you understand her baseline risk for carrying a fetus that has chromosomal abnormalities, including her age, the status of her other children, and other things in order to help you calculate a pretest probability. And so after that, the non invasive prenatal test takes that into consideration and returns a probability of carrying a fetus that might have those aberrations, and it's not a binary risk. It's, as I said, a continuous variable. So I think what you're proposing actually goes beyond what I wrote about in the article. I think it's a fabulous idea. And I think that in the near future, I can imagine that as natural language processing is exploding, and in general, large language models and the ability to extract features about a patient from the EMR are exploding, we might have a better stratification in general of patients into average risk, low risk, high risk, and really high risk, using EMR data, using real world data that could help us feed a really accurate picture of a patient's pre-test probability into this test, so that these tests could be further refined and further trained and validated on patients, taking into consideration more factors and help us improve the predictive power of the tests as they're returned in a report to the physician. So I think maybe you should even write an article about the idea just proposed. It's a great idea. Dr. Davide Soldato: So another aspect that I was really interested in is I've looked at one of the papers that you cited, and I wanted to discuss this with you as you are an expert on the topic. In one of the articles that you cited that used this type of test, they identified some of the cancers that we also normally identified with standard screening procedures, like breast or lung or colorectal. So for those cancers, we add a certain proportion, or like, for example, for breast cancer, a higher proportion identified with conventional screening. But still we had some other cancer that eluded those types of screening and were identified using liquid biopsy tools. So do you envision a strategy where we would use the screening methods that we already add as a complement to those liquid biopsies, or do you think that someday liquid biopsy could potentially completely substitute standard screening procedures?  Dr. Sana Raoof: I think we're too far from a day where liquid biopsies are going to replace standard of care screens. The scope scans and smears that the United States Preventive Services Task Force has recommended are gold standard screening interventions because, number one, for all of them, except for cervical cancer screening, we have randomized data with definitive endpoints that tell us that there are mortality benefits from doing those screens. We don't have that type of data yet from the world of multi-cancer early detection. And as we talked about earlier in this podcast, those tests are kind of designed with a different approach where they have higher sensitivity and much lower specificity than multi-cancer early detection tests.  So I think that the molecular cancer screening companies have done a very careful job of creating tests that are really more optimized to be complementary tests rather than a standalone catch all test, to have higher specificity at the cost of lower sensitivity. So I don't imagine a near future, at least not in my career, where we're going to stop doing colonoscopies and mammograms and pap smears. I don't think that that's going to happen. But I do think that whereas right now 75% of cancers that Americans die from, we lack cancer screening mechanisms for them, I think that that number has the potential to really drop. If in the next few years, one of these multi-cancer early detection tests is ultimately approved and covered, then I think that a lot more cancers could be detected by screening rather than by symptoms, and we might ultimately see a big stage shift.  Dr. Davide Soldato: Yeah, I think you're absolutely right. In the same article that I was mentioning before, there were several of those cancers which can be lethal if diagnosed at an advanced stage, that were diagnosed at an early stage, for example, ovarian cancer, bladder cancer. So I really think that we really have potentially the way to screen, or at least have a signal for cancer that currently we just diagnosed when symptoms associated with higher stage appear.  But moving on to turning the knobs on this type of test, and so going to the higher risk population, for example, cancer survivors, which is something that you speak a lot about in the manuscript. So you also discuss a little bit the question of whether we should use multi-cancer testing versus single cancer testing. So are we looking at a specific recurrence from that specific tumor, or are we looking at a general risk of cancer in a population that has a common risk factor, like tobacco? And so I was wondering if you think, and this is probably just your perception or just your opinion, that that is another way that the physician should turn the knob. Should we evaluate the risk of those cancer survivors and say, in this specific patient right now, the risk of recurrence is higher so I should use or I should be more in favor of a test that is more centered on the risk of recurrence versus I have a general risk of several cancers that could appear, and so should I use something that is more multi-cancer? This, of course, is merely speculative because we still don't have definitive data regarding the efficacy of this test. But it is just your perspective on this type of approach in the near future or not so near future.  Dr. Sana Raoof: Well, I think if we're speculating, then I think that the fantasy situation for any oncologist is that you have two types of liquid biopsies. One is a multi-cancer early detection liquid biopsy. And it would be great if you could select whether you want it to be optimized for highest NPV, negative predictive value, or highest PPV, positive predictive value. And then you also have a host of single cancer screening liquid biopsies that can help you specifically figure out if there's a recurrence of a single cancer type that you're suspicious about.   So, for example, in the article, I talk about how there will be clinical gray areas, and it's not always going to be obvious which test you should reach for. But one example that I think we can all relate to in the oncology community is you have some indeterminate imaging finding, and you don't know what to do about it. So, for example, you have a woman that has a history of breast cancer, has had no evidence of disease for a few years, now, has back pain. You do a spine MRI, you see a lesion. Maybe it's an atypical hemangioma that's causing pain, maybe it's a breast cancer metastasis. You're not sure. What should you do? Should you do a biopsy of that lesion in the spine? Should you wait and see if it grows and do another MRI in two or three months? What are your options? And so in this situation, I think we can all agree that if you had a liquid biopsy that was optimized for really high sensitivity, specifically for breast cancer, and had a very high negative predictive value, and if it came back negative, then in that setting, it might help you avoid an invasive test, like a biopsy in the spine, and give you a little bit more comfort as a physician to say, “You know what? I'm going to come back in two or three months and do another spine MRI. I'm going to see how this woman is feeling, and I don't need to biopsy this right now. Maybe it really is just hemangioma.”  Dr. Davide Soldato: And in this specific setting, let's take the same patient. So it's a female patient, she had a previous diagnosis of breast cancer. Do you think that there is a difference between tumor-informed tests, really based on the molecular aberration that the primary tumor had for these women, versus just a standard test that gives us information regarding the presence of breast cancer cells or not? And if you think that there is a difference, what would you think would be the advantage of one? And the disadvantages, for example, is a tumor informed essay more complex to obtain? Do we need more time? Is it more expensive versus a commercial test that is already available or something like this? This is my understanding as someone who's not so much in the topic, but I think that this is a point that many oncologists probably wonder about, and probably we should speak a little bit more about with someone who is an expert on the topic.  Dr. Sana Raoof: Absolutely. And I think that you've actually hit all of the major points on the head. So comparing a tumor informed versus a tumor agnostic test is like really comparing apples and oranges. A tumor informed test where you're starting with a patient's pathology and you are looking specifically for mutations and other molecular features that you know the patient has in their tumor, is going to, of course, result in a test that is, number one, more expensive and harder to make, but also, number two, more sensitive, more specific, more predictive, and in every way probably just more powerful than a test that is, in general, optimized for a single cancer type, but is almost certainly going to be trained and validated on people with a mix of histologies, a mix of molecular features, and will not be as sensitive or specific as a test that is actually informed by that single individual's tumor. One of the things that matters a lot to me is health equity in oncology. There are just huge disparities in outcomes in patients that are advantaged and disadvantaged. And it stems from lots of different things. In no small part, it stems from later stages of diagnosis in disadvantaged patients, and then even once you have a diagnosis, delays to confirmatory workup, delays to starting treatment, disparities in the treatments offered.  I don't imagine a world where everyone on earth is going to have access to tumor-informed liquid biopsies. I do imagine a future where tumor agnostic liquid biopsies, both for single and multi-cancer screening, should be a lot more economical than they are now, and should be more available for multiple cancer types, and should be more available to patients that aren't at just the Memorial Sloan Ketterings and the Dana-Farbers of the world. And so I do think that those types of off the shelf tests have the potential to really revolutionize the way that we work up suspicion of cancer, not just in advantaged patients, but also in patients that are diverse, in patients that are not at academic cancer centers, but at other cancer centers around the world. And I think it's a really exciting prospect.   Thinking about the chance of recurrence in the breast cancer patient is a perfect example of when you want to test that is optimized just for breast cancer, because you see something in the spine, you know her history, and you're less worried about a new primary and a new MET from that primary. But there are other situations that are also interesting to consider. For example, patients that have had lung cancer and have a history of smoking, because they've had a history of smoking, they're actually at risk for a dozen different cancers, not just lung cancer. And when you think about what we do to follow lung cancer survivors, we're just doing CTs of their chest and of course, physical exams. But the vast majority of cancers that people with lung cancer history will get may not be present in the field of view of a CT of the chest. They may also get renal cancer, bladder cancer, they might get leukemias, they might get pancreatic cancer. So there are a lot of things that you're not going to catch in a CT of the chest. And so in that situation, you care not only about recurrences, which in thoracic oncology, it's kind of a gaussian probability distribution, where the tail is almost close to 0 after five years, but also a uniform distribution of roughly 3% per year of a second cancer, a new primary cancer that goes on for the rest of their life. And so in that clinical setting, you can imagine that having an off the shelf multi-cancer early detection test may be dialed up for higher negative predictive value, would be extremely useful. Dr. Davide Soldato: Yeah, I totally agree, but thank you for clarifying these points, because I think that there is a little bit of confusion also in the oncology community, as this type of tests, they're also based on very complicated molecular biology, sometimes could be potentially integrated, and we could potentially integrate them in the clinic.  And so I wanted to close up with kind of a personal question. I was wondering how you came to be so interested in this field of molecular screening or early diagnosis and prevention associated with molecular data.  Dr. Sana Raoof: Well, it's an interesting story. I did my MD PhD at Harvard Medical School, and my PhD was in the opposite world from molecular cancer screening. I was designing drug combinations that could be used in advanced oncogene mutant lung cancers. And I thought I would become a medical oncologist and spend my life designing new systemic therapies for advanced malignancies. And what I saw every day in the lab during my PhD is drug resistance emerges and it's a process of evolution by natural selection happening on a cellular level. And although we have some really great slam dunk drugs that come to mind, for example EGFR inhibitors in certain lung cancers, immunotherapy in melanoma, on average, the median overall survival gain from all of the FDA approved drugs in the last 10 years is roughly two months.   By the end of my PhD, I really started feeling like, is the best use of my life to continue fighting a battle against natural selection in cancer cells, or is it a better strategy, to me, it seemed like a more sensical strategy to just try and find cancers in these patients earlier, when you don't have to engage with the complex signaling mechanisms of a cancer cells biology, and instead can just provide a definitive local intervention, like surgery or radiation, which already is curing many patients with non metastatic cancers. And as I looked around the world, I just didn't see that many people investing heavily in early detection research at the time. It was the very early days of multi-cancer early detection. And so I became involved with all of the groups, the companies, the organizations that were developing these tests, and really fell in love with, number one, just the concept of the tests, the concept of multi-cancer early detection, rather than single cancer screening alone, because no one knows what cancer they're ultimately going to get. But I also really fell in love with methylation biology, fragmentomics. I fell in love with the types of clinical trials that were being designed and the new types of endpoints that we have to think about when we're designing clinical trials for a multiverse of single cancer screening. And it's just such an exciting time in that community, it's the early days. So that's how I came to this space, and it's just the perfect time to be in this space, because everything is exploding.  Dr. Davide Soldato: Thank you very much. And thank you also for sharing the personal side of the story. Dr. Sana Raoof: Thank you so much. I'd like to thank Razelle Kurzrock, who's an amazing medical oncologist who's worked with me on two really fun papers so far, one on real world data, and this one on turning the knobs on liquid biopsies. It's always great to bounce ideas around about multi-cancer early detection with friends and collaborators, and Razelle did an absolutely amazing job helping write this piece.  Dr. Davide Soldato: So this brings us to the end of the episode. Thank you Dr. Raoof, for joining us and sharing more on your JCO article titled, ”Turning the Knobs on Screening Liquid Biopsies for High-Risk Populations: Potential for Dialing Down Invasive Procedures.”   If you enjoy our show, please leave us a rating and review, and be sure to come back for another episode.   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.   Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  Disclosures: Dr. Raoof Stock and Other Ownership Interests Company name: Illumina Radiopharmaceuticals Honoraria Company name: AstraZeneca Consulting or Advisory Role Company name: Verily Company name: GRAIL Company name: Exact Sciences Travel, Accommodations, Expenses Company name: Grail    

JCO PO author Dr. Samuel J. Klempner shares insights into his JCO PO article, “PD-L1 Immunohistochemistry in Gastric Cancer: Comparison of Combined Positive Score and Tumor Area Positivity across 28-8, 22C3, and SP263 assays”. Host Dr. Rafeh Naqash and Dr. Klempner discuss assessing the analytical comparability of three commercially available PD-L1 assays and two scoring algorithms used to assess PD-L1 status in gastric cancer samples. TRANSCRIPT  Dr. Abdul Rafeh Naqash: Hello and welcome to JCO Precision Oncology Conversations, where we bring you engaging conversations with authors of clinically relevant and highly significant JCO PO articles. I am your host, Dr. Abdul Rafeh Naqash, Social Media Editor for JCO Precision Oncology and Assistant Professor at the OU Health Stephenson Cancer Center. Today we are excited to be joined by Dr. Samuel J. Klempner, Director of Gastro Esophageal Medical Oncology and Assistant Professor at Harvard Medical School Mass Gen Cancer Center and author of the JCO Precision Oncology article, “PD-L1 Immunohistochemistry in Gastric Cancer: Comparison of Combined Positive Score and Tumor Area Positivity Across 28-8, 22C3, and SP263 Assays.” At the time of this recording, our guest disclosures will be linked in the transcript. Dr. Klempner, welcome to our podcast and thanks for joining us today.  Dr. Samuel J. Klempner: Happy to be here. Thanks for having me. Dr. Abdul Rafeh Naqash: For the sake of this podcast, we'll be using our first names. So, Sam, it was great to see you at ASCO recently, where I believe you presented these data as an abstract as well. Dr. Samuel J. Klempner: Yes, we had a poster presentation for this paper, which was published in parallel with the meeting. Dr. Abdul Rafeh Naqash: Congratulations, and I'm very happy that you chose JCO PO as the destination for these data. So we're going to be talking about a lot of different things today in the context of gastric cancer, which I know you treat very often in your clinic. So could you tell us what the treatment landscape for advanced gastric cancer currently is? Because that goes into the context of why I believe you and your colleagues went ahead with this project.  Dr. Samuel J. Klempner: Yeah, happy to. As you know, unfortunately, half or more of our patients, by the time they come to medical attention for a gastric or GE junction or esophageal adenocarcinomas, unfortunately have advanced disease, often metastatic at presentation. So we have this large population of patients with advanced disease, and over the last couple years, we've actually made some substantial advances in the management and survival of this population. This has been mainly driven by biomarker selection, whether it be adding immunotherapy on top of HER2 therapy, whether it be testing for claudin and seeing the results with claudin directed therapies. And perhaps the vast majority of patients are potentially eligible for immune checkpoint inhibitors. We've seen several phase three trials, perhaps highlighted by CheckMate 649, KEYNOTE 859, rationale studies confirming that there are populations of patients who derive significant survival advantages from the addition of anti PD-1 on top of chemotherapy. So the landscape has really evolved into a biomarker directed world, which is exactly what we hope, because ultimately, the goal is, of course, to match patients with the best drugs at the right time. And that's really the background of where this analytical effort came from.  Dr. Abdul Rafeh Naqash: Thank you for giving us that overview. Going to the second part, which, as you mentioned in your initial overview about the role of immunotherapy, and as we all know, immunotherapy has changed the treatment landscape for a lot of different tumor types. And as clinicians, we often see or ask, what is the PD-L1 positivity for, let's say, lung cancer, which is what I treat, and gastric cancer, which is what you treat. Some of the nuances that we don't necessarily go into when we're looking at those reports is the combined positivity score, the tumor proportion score, or the tumor area positivity. Could you give us an understanding, for the sake of our audience or for the sake of our trainees who might be listening to this podcast, what the CPS, or what the TAP  mean and where they are used in the treatment landscape for biomarker selection in the context of gastric cancer? And how do you approach the different cutoffs for CPS when you're treating an individual in the standard of care setting for gastric cancer? Dr. Samuel J. Klempner: For sure, happy to. So I think eventually it all comes back to patients. When we're sitting in a clinic room with the patient, we want to be able to have features about the tumor that's going to tell us if a therapy is more or less likely to work, maybe if there's a prognostic implication so we have predictive and prognostic biomarkers. And PD-L1 expression does not appear to be particularly prognostic, but it does appear to be predictive of benefit from immune checkpoint inhibitors. Therefore, all of the phase 3 trials that we've seen in some way have linked the biomarker expression to outcomes, whether it's the primary endpoint, whether it's post hoc retrospective analyses, etc. What we've seen is that all of these phase 3 trials have largely used different antibodies to define PD-L1 strata within the trial. So whether that's 22C3,  whether it's 28-8, whether it's 263, those are the predominant antibody clones used to examine PD-L1 expression in tumor samples. And it's been pretty clear across these large phase 3 trials that there is a trend with increasing PD-L1 expression and increasing magnitude of benefit. We see this in the improved hazard ratios in the CPS greater than five or greater than ten versus less than one, etcetera.  However, the scoring systems have varied. There is TPS tumor positivity, which only accounts for tumor cells. There is combined positive score, which accounts for tumor cells and mononuclear infiltrates and involves counting cells. And then perhaps the most recent one is the tumor area positivity, which is essentially a non counting method to look broadly at the area of the sample that is expressing PD-L1. It was on this background that we said, is there analytical concordance among the main antibodies? Our work does not address whether there is difference in clinical outcomes between testing 28-8 and 22C3 and SP263. It is simply a pure analytical comparison of the three antibodies. Is a CPS 5, when you call it by 28-8, somewhat agreeable to a TPS or a TAP greater than five with the same antibody and with a different antibody. So we felt that this was kind of a question that hadn't really been fully addressed in the field and may help contextualize results for clinicians and ultimately cross trial comparisons.  Dr. Abdul Rafeh Naqash: Thank you for that explanation. And you bring forth a very important question. And I remember this example of a patient with lung cancer who had tissue NGS done, and they had a limited gene panel with PD-L1 testing sent that showed a PD-L1 of close to 15 or 20%, and then another NGS panel with a different antibody, suggesting that they had a PD-L1 of close to 60-70%, which significantly changes the overall approach for treatment in the context of blood cancer. Is that something that you experience in gastric cancer also, in terms of variability for CPS, determining what treatment combinations you might be able to put an individual patient on? Dr. Samuel J. Klempner: It's rare that we have samples at any institution tested in multiple methods, but these types of papers and others had looked at some stuff similar and prior to our publication, but we know that there is both spatial heterogeneity. So if you test a tumor versus metastasis, you may have different PD-L1 scoring even in regions of large samples, like surgical resections, there will be some intra tumor heterogeneity in regions of expression. And then we also know that sometimes after therapy, for example, post radiation, there's some data that at the time of surgery, the PD-L1 expression may be higher than what the presurgical sample was. So there's a lot of variables that are factored in. But one thing that wasn't really well known is, across the standard antibodies, how well is the inter assay comparison? There had been some work from a group in Singapore, a very nice paper suggesting that at the higher cut points, the agreement was pretty good across the assays, CPS greater than 5 and greater than 10, and maybe slightly less so at the lower. They had used a different method, which was not really what is standard, and they had used multiplex immunofluorescence or IHC. This is not a validated method for PD-L1 scoring. So that was an open question, sort of. Although they laid a very important piece of data down, we wanted to use the most standard assays and essentially do a very similar analysis, but using the standard scoring criteria. Dr. Abdul Rafeh Naqash: Very interesting. So, could you walk us through the approach of how you looked at this question, what kind of samples you used and what kind of testing algorithms you implemented to look at the cross validation of these three different antibodies? Dr. Samuel J. Klempner: The antibodies were chosen primarily because those are the standard ones that either have companion diagnostics or have been used most commonly in phase 3 trials. So 22C3 has most commonly been linked to pembrolizumab, 28-8 to nivolumab, and 263 used with Roche and Genentech trials primarily. And so we selected the antibodies based on the common use. We selected the scoring systems of CPS and TAP, again based on the most commonly used and validated scoring algorithms in gastric cancer. And then, although most patients in clinic and metastatic disease present with biopsy samples from the primary tumor, there may be some limitations in biopsy samples in terms of small amount of material and ability to reliably count 100 cells, etc., for CPS. So we actually use surgically resected samples from a commercial biobank, 100 samples, and essentially 28-8 was really the reference. And we picked samples that, using 28-8 CPS PD-L1 expression represented the entire spectrum, meaning we had CPS less than 1, we had greater than 1 and less than 5, greater than 5 and less than 10, and greater than 10, so that we could compare across these different strata, because those are the most common strata that have been used in clinical trials and linked to magnitude of benefit. Dr. Abdul Rafeh Naqash: And something that, interestingly, I see here when we go to some of the results, and I'm pretty sure you'll talk about the concordance, is the correlation coefficient seems to increase as the percentage positivity increases for a certain antibody. Could you try to help us understand why that might be the case? Is it because it's easier for the pathologist to look at the slide when there is a certain level of positivity that crosses a certain threshold? Or could there be some other factors that are not well understood. Dr. Samuel J. Klempner: Yeah, it's a totally good question, and I think it's something that's seen in other IHC biomarkers as well. If you look at HER2, you'll see some similar trends. The agreement at IHC 3+ is pretty good and greater than it is at lower cut points. And having talked to multiple pathologists, and I'm not a pathologist, we had three pathologists scoring all of these samples, and essentially, it's what you might expect. It is just easier when there's a lot of the marker. It is easier to judge the high extremes of the strata. So the agreement at greater than 10 is quite good, and this has already been shown by others. It's just an easier thing to score for anyone. The agreement is better across all of the assays at higher cut points, whether it's TAP greater than 10% or CPS greater than 10%. And you can see that pretty clearly in our data, and it's also been shown in other data sets looking at roughly similar questions in other tumor types.  Dr. Abdul Rafeh Naqash: Going to the interesting results that you have in this paper, could you highlight for us some of the important findings that you had and put them into context of what their clinical implications may be? Dr. Samuel J. Klempner: Yeah, I think I'll start with the clinical implications so that what clinicians, and we're both clinicians, what we want to know is, if I have a report that says the CPS is greater than 1 and it's done with a 22C3 test, is that also likely to be greater than one if it had been done with a 28-8 test or scored with a different algorithm - CPS versus TAP? So, essentially, some degree of confidence on the interchangeability between the assays themselves, that is really the clinical implication. And so, to accomplish this, we set out to basically do the comparisons you'd have to do to convince yourself that that is true. So you take samples against a reference range, in this case, across the PD-L1 strata, you pick a reference test, in this case, 28-8, you have one pathologist be the start, and then you compare other pathologists against each other and that person, and you look. And in the pathology literature, they have strata of agreement which tend to go from poor, moderate, good to excellent. And these are sort of accepted standards in the pathology world about inter reader agreement. So between one pathologist and another, and things that are moderate or good are considered essentially acceptable at interchangeable levels.  And so, as you suggested, at the higher cut points, the agreement is very good. The clinical interpretation of that is that if you get a TAP greater than 10% scored on a 22C3 antibody on a Dako staining system, you can feel relatively confident that that would also be called a TAP or a CPS greater than 10 by a 28-8 antibody, suggesting there is good agreement between the two antibodies at that cut point. As you move down, there is a little bit less agreement, and that is consistent with what's been shown before. But in our data set, the agreement was still pretty good across all three of the antibody clones, even at the lower cut point, so greater than 1% for TAP or CPS greater than 1. And that provides, I think, some reassurance to clinicians that whatever test their own pathology lab is using, if it's one of these three assays, they can provide some degree of confidence that what they're seeing would be similar to what they were seeing if it had been done with another test. Dr. Abdul Rafeh Naqash: I think that that is very important, because even though we do want broad testing in general for metastatic tumors, as you probably will agree with, but there's a lot of practices still that institutions tend to do their own testing with limited gene panels or even IHCs. So I think to put that in the context of your study, as you said, if you have a certain antibody that is positive, as you've shown, then that also likely means that with another antibody that your institution may not test for, it's likely the tumor sample is likely going to be positive at a similar level.  So I think you also used digital pathology as part of this project, even though that may not be the most important aspect. As we move slowly and steadily towards artificial intelligence and machine learning, could you tell us how you incorporated the digital assessments and how you utilize them to correlate with the pathologist assessment and the futuristic perspective of how we could eventually try to incorporate digital pathology assessments for this kind of staining approach, which might limit interobserver operability differences as well as time constraints? Dr. Samuel J. Klempner: I hope I can do this part justice, because, again, I'm not a pathologist. But the digital imaging analysis was really essentially used as a quality check and verification tool in our own paper. Our intent was not to establish DIA directly as a superior methodology to TAP or CPS, but simply to provide ourselves some degree of confidence in the staining pattern and distribution across the three assays, and whether or not this would generate significant differences in what the PD-L1 score would have been called. And so, the bottom line is, the digital imaging analysis suggested there were very minor differences across the three assays in terms of, like, percent cell positivity, which is one of the main readouts, and the mean difference was actually quite small. So we felt that the digital imaging analysis, which was really considered somewhat exploratory in our own work, supported what we saw with the pathology comparators read in traditional methods. I think it sets somewhat of an initial pilot data benchmark to say that maybe we can think about moving tools like digital imaging analyses forward in terms of PD-L1 scoring approaches in the future. But it does not provide adequate data to say that we can do this now or we have enough samples and enough comparisons to say that, “Hey, for sure, digital imaging is equivalent to pathology reading.” I think that we're getting there and our data supports that that may ultimately be the conclusion, but for us it was really essentially an orthogonal support and sanity check for our traditional approach, which is, of course, a pathologist based scoring. So supportive and suggestive, but not definitively conclusive. Dr. Abdul Rafeh Naqash: Definitely early days for visual pathology assessments, but I think that it's a very rapidly evolving field, and hopefully we'll see more of this in the next few years, as well as incorporating some assessments into clinical trials.  Now, shifting away from your honorary pathologist role as part of this project to your actual role as a clinician investigator/clinician scientist, could you tell us your career trajectory, how you started, how you've self paced yourself, and how you've tried to mentor certain different individuals in your current role? Dr. Samuel J. Klempner: Yeah, I remember my grandfather and other people telling me, just try to leave it a little bit better than you found it. And so that's, I think, a guiding principle. I hope that at the end of my own career, I can leave oncology a little bit better than when I started. I think the best way to do that is to mentor and train the next generation who are going to drive these practices. I started, like many others, personally touched by cancer in my family, which started me on a journey towards oncology, was somewhat frustrated by the lack of options available to my mom, and then became deeply interested in the science and how come we knew so little about cancer, so spent a fair amount of time in labs, and had a really formative experience with Lew Cantley looking at PI3 kinase resistance and signal transduction, and wanted to learn to speak the language and interact with people driving the lab based work. And that's been something I've tried to keep as central to my career as someone who has a very strong translational interest.  And so I try to think of ways that I think we can learn from every single patient and every subgroup. I mean, for example, in our own work here, it's very unclear if there's a biology linked to the different PD-L1 strata. So for example, does a PD-L1 CPS greater than 10 tumor have a very high interferon gene signature? Or are there features of the T cells that are different between a CPS 10 or higher versus a less than 1? So PD-L1 is a biomarker, but is it really telling us about biology? And so these are the types of questions that I try to stimulate in all the residents and fellows and hopefully it will drive translational projects. But I think just having the conversations and asking the questions and talking to people. I mean, I love the ASCO Career Lounge and always try to do that when possible. I know you do the same. I think staying curious is really the thing that I try to remain in life and also in my career and have fun and enjoy with your colleagues. And I think that will make us all better researchers and ultimately translate to better outcomes for our patients, which is, of course, why we all do this. Dr. Abdul Rafeh Naqash: Wonderfully said Sam, thank you so much. Thanks again for choosing JCO PO as the final destination for your work. Hopefully we see more of the similar work that you do in your field in JCO PO. And thank you for talking to us about your journey as well.  Dr. Samuel J. Klempner: Yes, thanks for having me. I'll talk to you sometime soon.  Dr. Abdul Rafeh Naqash: Thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or review, and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcast.   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.     Disclosures Dr. Klempner Stock and Ownership Interests TP Therapeutics Nuvalent, Inc Honoraria Merck Serono Consulting or Advisory Role Atellas Pharma Bristol-Myers Squibb Merck Daiichi Sankyo/UCB Japan Sanofi/Aventis Mersana Exact Sciences Novartis SERVIER AstraZeneca Amgen I-Mab iho Oncology    

Drs. Shaalan Beg and Travis Osterman discuss a machine learning model, recently featured in JCO Clinical Cancer Informatics, that uses electronic health record data to accurately predict the effectiveness and toxicity of treatment with immune checkpoint inhibitors. The new AI model can be used to provide a personalized risk-benefit profile, inform therapeutic decision-making, and improve clinical trial cohort selection.   TRANSCRIPT Dr. Shaalan Beg: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Shaalan Beg, your guest host for today. I am an adjunct associate professor at UT Southwestern's Simmons Comprehensive Cancer Center.  Cancer immunotherapy has transformed the treatment landscape by providing new and effective treatment options for many solid and hematologic malignancies. But while many patients experience a remarkable response to immune checkpoint inhibitors, other patients can suffer life-threatening immune checkpoint toxicities. Today, we will be discussing a machine learning solution that can assess a patient's immune checkpoint inhibitor risk-benefit profile based primarily on routinely collected structured electronic health record data. This novel AI solution was recently featured in JCO Clinical Cancer Informatics, and I am delighted to welcome one of the report's authors, Dr. Travis Osterman. He is an associate vice president for research informatics and associate professor in the Department of Biomedical Informatics and the Division of Hematology Oncology at Vanderbilt University Medical Center in Nashville, Tennessee. Dr. Osterman also serves as the director of cancer clinical informatics at the Vanderbilt Ingram Cancer Center.  Our full disclosures are available in the transcript of this episode, and disclosures related to all episodes of the podcast are available at asco.org/DNpod.  Dr. Osterman, it's great to have you on the podcast today.   Dr. Travis Osterman: Thanks, Shaalan. It's great to be here. Thank you for the invitation.   Dr. Shaalan Beg: Congratulations on your recently published article in the JCO CCI titled "Prediction of Effectiveness and Toxicities of Immune Checkpoint Inhibitors Using Real World Patient Data." Why did you decide to address this specific problem?   Dr. Travis Osterman: I am a practicing medical oncologist at Vanderbilt, I specialize in thoracic malignancies. Immunotherapy has been a significant part of my practice from the beginning. And I think for all of us, we have patients in our practices that are tremendous responders. I have stories of my patients, a few of which, at least, are able to get years of benefit even after stopping therapy, and potentially some even stage 4 patients that are amazingly seemingly cured after their treatments. But I also have patients that experience severe toxicities, some of those are life-threatening or life ending, but many of those carry morbidity. In my population, I see a lot of pneumonitis, and that really alters patients' quality of life. And the biggest conversation I have with patients is: “How do I know which of these outcomes I'm going to have, if I'm going to get benefits from these therapies or am I going to get one of these side effects or toxicities?” And we set out to try to answer that question with data.   Dr. Shaalan Beg: When electronic medical records started to make their way into the clinic, I remember all of us thinking about the wonderful applications where we could use the data to help guide the clinical care, assign the right treatment for the right patient at the right time, and learn from other patients' experiences to improve the care of the person who's in front of us. And my personal opinion is that we haven't realized our electronic medical records' potential to that extent. And efforts like the one you published in JCO CCI is the culmination of one of the efforts, and I can only imagine how much time and effort it must have taken to develop that and we're hoping is the first of many more to come. For our listeners, can you talk us through the steps required to develop such a tool, and why now is the right time, and why we're starting to see these evolve?   Dr. Travis Osterman: This project would not have been possible 20 years ago. It relies on having what we would call structured data available for our patients that are receiving cancer care, so that's vital signs, laboratory values, and diagnoses, all of the things that we routinely collect in the electronic health record. So that is step 1. This project required that those systems be not just in place at academic centers but be widely available because our goal is to set up systems that will be able to transform cancer care, not just at academic institutions, but for the entire practice of oncology.  The second piece is you need enough data to be able to train these models. And so, we needed to be practicing with checkpoint inhibitors long enough to see patients that had toxicities, to see patients that had benefit, and then to jump into the data science of actually trying to learn from them. And so this really was the culmination of systems put in place by a lot of people before us and then really the right time [when] we started to have now enough data to really start to learn from.   Dr. Shaalan Beg: The publication discusses the steps of how you validated your tool. Talk me through how you see this being applied to the point of care for the next time you are about to start an immune checkpoint inhibitor for your lung cancer patient?   Dr. Travis Osterman: I think there are two different primary lanes that these types of models can be applied. In the drug development space, I think many of us are familiar that many assets, many drugs that are in the development pipeline are halted because of adverse events in toxicity profiles, but we also realize that not everyone gets those toxicities. And so we envision a future where before a drug that's in the drug development pipeline is taken out of the development pipeline, potentially, you could screen patients that are at lowest risks of actually having side effects from that immunotherapy and only screen those patients into the trial and that would potentially make more drugs available to more patients going forward. So I think that that's 1 lane.  I think the other lane in clinical practice is, let's say that I'm treating a patient who we determine has an increased risk for colitis. Instead of only seeing that patient back in 3 weeks, potentially, now, what if I had one of our nurse navigators, call the patient at weekly check-ins between visits to check in and see whether or not they were having any episodes of diarrhea and trying to intervene earlier. That might allow us to keep patients both out of the hospital, out of the emergency department to treat their symptoms more quickly to decrease the severity of their toxicity and keep them on treatments, especially if they're receiving benefit from it. So, I think there's an opportunity to improve both drug development and making more drugs available to patients and then also to identify patients that are at risk for toxicity, and then to do interventions to help mitigate those risks. Really, the idea of precision risk mitigation.   Dr. Shaalan Beg: One of the problems with electronic medical record-based tools in the past has been that they don't evolve with time. We develop it, we set it, we deploy it, and it almost feels, to the users at least, that it stops evolving after that. With novel therapeutic agents coming into the clinic, we're seeing new ADCs, new novel checkpoint inhibitors entering the market. How do you envision tools such as yours to be refreshed so they can stay relevant with the modern armamentarium of medications which are being used?   Dr. Travis Osterman: So, if you ask any data scientist, the most requested item they will ask for is more data. And so, this initial set of models that we've described in this publication were trained exclusively on a single institution's data at Vanderbilt University Medical Center as we continue both to see more patients here, and then ideally look forward to collaborations with other centers. We expect that these models will continue to be refined and that the performance will improve as we increase the amount of training data, and we hope that that will do 2 things. One, it will counteract the kind of model drift that you described. But then two, it will allow us to ask some more specific questions that honestly, we weren't really powered to answer in our study here. For instance, we didn't look at cardiac toxicity, which is a concern if you're giving a CTLA-4 along with a PD-1 or PD-L1 inhibitor more so than single agent immunotherapy. We just don't have enough events to be able to train models on that. But with future collaborations, that would be a question we would love to tackle as well.  One of the things that's interesting about the implementation of these models is that we found many of the features that I would have expected to find as a practicing oncologist. For instance, when we're trying to predict the toxicity of pneumonitis inflammation of the lung, I as an oncologist would think that many of my patients that have COPD or interstitial lung disease at baseline seem to be at a higher risk. And so that's one of the features that I was looking to come out in the model. And that's exactly what we found. That was one of the contributing features that helps us predict a higher risk of pneumonitis. But what's interesting is that's certainly not the only feature; there end up being about a dozen features that are in that space that help predict that toxicity.   Similarly, for colitis, we found that the combination of receiving a CTLA-4 inhibitor in addition to a PD-1 or PD-L1 inhibitor, that combination together, which would increase risk for colitis, which is well-documented in our literature. So these models are not entirely black boxes. We've published the top features of these models that contribute to our predictions. And I think clinically the challenge for me has always been if I have a patient who has COPD, but it's pretty well-controlled and their O2 sat is normal, how does that patient's risk bring pneumonitis compared to someone who has poorly controlled COPD with low O2 sat at baseline, etc.? And so these models are really designed to help tease out some of those nuances.   Dr. Shaalan Beg: There are so many wonderful applications to use preexisting data that can improve the lives of our patients and frankly that can improve the work experience for clinicians. They can be used for risk stratification using these preexisting data. Can you talk a little bit about what are the barriers that people face or that your team faced in developing these tools, and what has changed or what's expected to change in the coming years to allow people to continue developing tools such as what was described?   Dr. Travis Osterman: I think it's important to realize that we are not unique in addressing this problem. This is a problem that I think has been a focal point of our cancer informatics community for the better part of the last, probably, decade. I think one of the things that distinguishes the work that we've done here is really this idea of clinical utility. And what I mean is we focused on data that would be collected at any routine oncology visit in the U.S., and I would argue worldwide, to use as features in our model. So, we're not running complex genetic testing that may or may not be paid for. We're not asking for new laboratory values to be sent or for extensive questionnaires that aren't already in clinical practice. We're using pieces that are already being connected into the pipeline of oncology practices, and I think that's one of the differentiators of this project versus many others in this space.  Right now, these are only EHR data. We have a part of our project that's looking at imaging data and whether that adds value. But one of the pieces that I always advocate for, if we're going to ask practices for instance to upload these imaging files or to send a CD to a central location to improve the outcome, that's harder to work into an oncologist workflow than if all the data are already there in the health record and you can click a button and calculate this person's risk profile. And so, we've really tried to be pragmatic about our approach as we've entered this realm and that's been a real focus of our team.   Dr. Shaalan Beg: Many of the listeners of today's podcast are busy clinicians, and you talked about how the idea for this project came from the problem you witnessed in your clinic. How can clinicians continue to be involved in such initiatives or drive these initiatives at their own institutions, in office situations where they may not have the resources that your team has? Can you speak to national efforts or collaborations in this regard?   Dr. Travis Osterman: Yeah. So, first of all, I would invite really anyone to reach out to our team, if they're in a position where they'll be interested in validating our models at their local institutions. We would be happy to work with them to provide the models to see how they perform on their data sets. I think that that's an important part of the academic review and informatics is to see how these models translate into other health care settings. And we also are interested to make sure that what I said in the prior discussion is correct, that we're only incorporating things that other institutions already have. So I think that that's certainly one.  The second is a part of a large National Cancer Data standard project called mCODE, the Minimal Common Oncology Data Elements, I chair that executive committee. And one of the pieces of that is trying to find a way to make all of these kinds of structured data interoperable between health records. And so I would just encourage all of my colleagues to always advocate for interoperability and, when there's an option, to store data in a way that makes that data more easily shared in the same formats between institutions. I think that that will pay many dividends for our field going forward. And I just want to plug all the team at mCODE for their work in this and maybe there'll be an integration and connection between mCODE and our project in the future.   Dr. Shaalan Beg: Thank you very much Dr. Osterman for sharing your insights with us today on the ASCO Daily News Podcast.   Dr. Travis Osterman: Thanks, Shaalan. Have a great day.   Dr. Shaalan Beg: And thank you to all our listeners for your time today. You'll find a link to Dr. Osterman's article in the transcript of this episode. And if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcast.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.   Find out more about today's speakers: Dr. Shaalan Beg @ShaalanBeg Dr. Travis Osterman @TravisOsterman   Follow ASCO on social media:  @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn    Disclosures: Dr. Shaalan Beg: Employment: Science 37 Consulting or Advisory Role: Ipsen, Array BioPharma, AstraZeneca/MedImmune, Cancer Commons, Legend Biotech, Foundation Medicine Research Funding (Inst.): Bristol-Myers Squibb, AstraZeneca/MedImmune, Merck Serono, Five Prime Therapeutics, MedImmune, Genentech, Immunesensor, Tolero Pharmaceuticals   Dr. Travis Osterman: Stock and Other Ownership Interests: Faculty Coaching Honoraria: Amazon Web Services Consulting or Advisory Role: eHealth, AstraZeneca, Outcomes Insights, Biodesix, MD Outlook, GenomOncology, Cota Healthcare, Flagship Biosciences, Microsoft, Dedham Group, Oncollege Research Funding: GE Healthcare, Microsoft, IBM Watson Health Travel, Accommodations, Expenses: GE Healthcare, Amazon Web Services

In this episode, we are joined by Drs. Jennifer Thorne and Parisa Emami to discuss diagnostic and therapeutic approaches in the management of uveitic CNV.Disclosures:Dr. Kopplin: NoneDr. Thomas: Consultant for Allergan,  GenentechDr. Thorne: NoneDr. Emami: Consultant for Genentech

MedLink Neurology Podcast is delighted to feature selected episodes from BrainWaves, courtesy of James E Siegler MD, its originator and host. BrainWaves is an academic audio podcast whose mission is to educate medical providers through clinical cases and topical reviews in neurology, medicine, and the humanities, and episodes originally aired from 2016 to 2021. Originally released: March 29, 2018 What does a brain look like in a patient with a functional movement disorder? Pretty normal, it turns out. But beneath the normal anatomy is a storm of aberrant signaling. Dr. Mark Hallett, Chief of the Human Motor Control Section of the NIH, describes the underlying neurophysiology in this spectrum of disorders. Produced by James E Siegler. Music by Damiano Baldoni, Kevin MacLeod, Ondrosik, and the Philadelphia String Quartet. Voiceover by Erika Mejia. BrainWaves' podcasts and online content are intended for medical education only and should not be used for clinical decision-making. REFERENCES Maurer CW, LaFaver K, Ameli R, Epstein SA, Hallett M, Horovitz SG. Impaired self-agency in functional movement disorders: a resting-state fMRI study. Neurology 2016;87(6):564-70. PMID 27385746Nahab FB, Kundu P, Gallea C, et al. The neural processes underlying self-agency. Cereb Cortex 2011;21(1):48-55. PMID 20378581Vuilleumier P, Chicherio C, Assal F, Schwartz S, Slosman D, Landis T. Functional neuroanatomical correlates of hysterical sensorimotor loss. Brain 2001;124(Pt 6):1077-90. Erratum in: Brain 2016;139(Pt 5):e29. PMID 11353724 DISCLOSURES Dr. Hallett receives funding from the Intramural program of the National Institute of Neurological Disorders and Stroke. No relevant conflicts of interest are present. He serves as Chair of the Medical Advisory Board for and receives honoraria and funding for travel from the Neurotoxin Institute. He may accrue revenue on US Patent: Immunotoxin (MAB-Ricin) for the treatment of focal movement disorders, and US Patent: Coil for Magnetic Stimulation and methods for using the same (H-coil); in relation to the latter, he has received license fee payments from the NIH (from Brainsway) for licensing of this patent. Supplemental research funds have been granted by BCN Peptides, S.A., for treatment studies of blepharospasm; Medtronics, Inc., for studies of deep brain stimulation; UniQure for a clinical trial of AAV2-GDNF for Parkinson Disease; Merz for treatment studies of focal hand dystonia; and Allergan for studies of methods to inject botulinum toxins. Jim is lucky enough to have no relevant competing financial interests.  We believe that the principles expressed or implied in the podcast remain valid, but certain details may be superseded by evolving knowledge since the episode's original release date.

In this episode, we are joined by Drs. Arjun Sood and Sruthi Arepalli to discuss diagnostic and therapeutic approaches in the management of uveitic macular edema.Disclosures:Dr. Kopplin: Principal Investigator in clinical study sponsored by RocheDr. Thomas: Principal Investigator in clinical studies sponsored by Roche and Alimera. Consultant for Alimera, Allergan, EyePoint Dr. Sood: Consultant for Alimera and EyePointDr. Arepalli: Consultant for EyePoint

Dr. Daniel Ambinder (CardioNerds Co-Founder), Dr. Kelly Arps (Series Co-Chair and EP fellow at Duke University), Dr. Stephanie Fuentes Rojas (FIT Lead and EP fellow at Houston Methodist), and Dr. Ingrid Hsiung (Cardiology Fellow at Baylor Scott & White Health) discuss situational assessment of stroke and bleeding risk with expert faculty Dr. Hafiza Khan (Electrophysiologist at Baylor Scott & White Health). In this episode, we discuss stroke and bleeding risk in specific situations such as prior to cardioversion, triggered episodes, and perioperatively. These are scenarios that are commonly encountered and pose specific challenges. Episode notes were drafted by Dr. Stephanie Fuentes. Audio editing by CardioNerds Academy Intern, Dr. Maryam Barkhordarian. This CardioNerds Atrial Fibrillation series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Kelly Arps and Dr. Colin Blumenthal. This series is supported by an educational grant from the Bristol Myers Squibb and Pfizer Alliance. All CardioNerds content is planned, produced, and reviewed solely by CardioNerds. We have collaborated with VCU Health to provide CME. Claim free CME here! Disclosures: Dr. Ellis discloses grant or research support from Boston Scientific, Abbott-St Jude, advisor for Atricure and Medtronic. CardioNerds Atrial Fibrillation PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls and Quotes - Atrial Fibrillation: Situational Assessment of Stroke and Bleeding Risk In patients with persistent atrial fibrillation with tachycardia induced cardiomyopathy, timely restoration of normal rhythm is important. In patients not on established oral anticoagulation one option is to wait 3 weeks on oral anticoagulation prior to considering cardioversion. Another option is to pursue TEE prior to cardioversion as TEE is currently the gold standard imaging modality to exclude a LAA thrombus. Following cardioversion (chemical or electrical), anticoagulation must not be interrupted for 4 weeks due to atrial stunning. This is especially true for patients who have been in atrial fibrillation for an extended period of time. Individualizing assessment of stroke and bleeding risk is imperative when determining perioperative anticoagulation (AC) management. ACC has a helpful app (ManageAnticoag App) to make this easier. When considering AC in triggered atrial fibrillation (e.g., pneumonia, sepsis), it is important to consider the substrate that made the patient susceptible to developing atrial fibrillation. AC is favored in patients with high CHA2DS2-VAsC score and many traditional risk factors for atrial fibrillation as they are at high risk for future development of atrial fibrillation. Atrial fibrillation is a marker of poor outcomes in patients who have undergone coronary artery bypass graft (CABG) surgery. It is unclear if patients should be started on long-term AC for new onset atrial fibrillation after CABG regardless of risk factors. This is currently being investigated in the PACES trial. Notes - Atrial Fibrillation: Situational Assessment of Stroke and Bleeding Risk How do we choose an imaging modality for excluding LAA thrombus exclusion prior to cardioversion? TEE is the gold standard. It also provides other information that is important for management of atrial fibrillation (e.g. LA size/volume, presence/degree of mitral regurgitation/stenosis, ejection fraction). Gated cardiac CTA may have a growing role for evaluation of LAA thrombus. What is the data behind the recommendation for uninterrupted AC following cardioversion and what is atrial stunning? All patients should be anticoagulated for four weeks after cardioversion,

Dr. John Sweetenham and Dr. Neeraj Agarwal discuss advances across the spectrum of malignancies, including key studies in precision oncology and disparities in cancer care in advance of the 2023 ASCO Annual Meeting.  TRANSCRIPT Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham, now the associate director for cancer network clinical affairs at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center, and host of the ASCO Daily News Podcast. I'm delighted to welcome Dr. Neeraj Agarwal, director of the Genitourinary Oncology Program and a professor of medicine at the University of Utah Huntsman Cancer Institute, who is editor-in-chief of the ASCO Daily News.  Today we'll be discussing some key advances across the spectrum of malignancies, as well as novel approaches in precision medicine and cancer disparities that will be featured at the 2023 ASCO Annual Meeting.  Our full disclosures are available in the transcript of this episode, and disclosures of all guests on the podcast can be found on our transcripts at asco.org/DNpod.  Neeraj, it's great to have you back on the podcast today. Dr. Neeraj Agarwal: Thank you so much, John, for having me. Dr. John Sweetenham: Neeraj, let's begin by discussing some practice-changing phase 3 trials, starting with Abstract 5500, the KEYNOTE-826 study. This study reports the final overall survival results from a randomized, double-blind, phase 3 study of pembrolizumab plus chemotherapy versus placebo plus chemotherapy for first-line treatment of persistent, recurrent, or metastatic cervical cancer, which will be presented by Dr. Bradley Monk.  Dr. Neeraj Agarwal: I'd be happy to. The initial analysis of the KEYNOTE-826 study revealed that first-line pembrolizumab plus chemotherapy provided significant improvements in the overall survival and progression-free survival compared to placebo plus chemotherapy in patients with metastatic, persistent, or recurrent cervical cancer who had not previously received systemic chemotherapy and were not candidates for curative treatments such as surgery or radiation. In this study, patients were randomly assigned in a 1:1 ratio to receive pembrolizumab or placebo at 200 milligrams every three weeks for up to 35 cycles, along with chemotherapy with paclitaxel, plus a platinum therapy with or without bevacizumab.   From November 2018 to January 2020, 617 patients were enrolled with 308 receiving pembrolizumab plus chemotherapy and 309 patients receiving placebo plus chemotherapy. At the data cutoff of October 3, 2022, the median follow-up was 39 months. At this protocol-specified final overall survival analysis, pembrolizumab plus chemotherapy treatment continues to show a significant improvement in overall survival and progression-free survival, regardless of whether patients receive bevacizumab or not. The incidence of grade 3 or more adverse events was higher in the pembrolizumab plus chemotherapy arm than the placebo plus chemotherapy arm, with the most common adverse event being anemia, neutropenia, and hypertension. Dr. John Sweetenham: These are exciting data, Neeraj. So the main message from this trial is that pembrolizumab plus chemotherapy, with or without bevacizumab, can now be considered as standard of care for first-line treatment of persistent, recurrent, or metastatic cervical cancer. Dr. Neeraj Agarwal: Yes, I agree, John. Now, moving on to a different common type of cancer, let's discuss Abstract 1001, titled “Second-Line Endocrine Therapy with or without Palbociclib Maintenance in Patients with Hormone Receptor-Positive/HER2-Negative Advanced Breast Cancer: Results from the PALMIRA Trial,” which will be discussed by Dr. Antonio Llombart-Cussac. So, John, based on this abstract, can you please tell us about the role of palbociclib after prior progression on this drug? Dr. John Sweetenham: Yes. In this study, the authors aimed to determine if palbociclib maintenance with an alternative endocrine therapy improves the anti-tumor activity of second-line treatment in patients with endocrine-sensitive hormone receptor-positive and HER2-negative advanced breast cancer who had disease progression to first-line treatment with palbociclib in combination with endocrine therapy. After including 198 patients in the trial with a 2:1 randomization, 136 patients received palbociclib with endocrine therapy and 62 patients received endocrine therapy alone. And at a median follow-up of 8.7 months, the primary endpoint of progression-free survival was not met with a median progression-free survival of 4.2 months in the palbociclib-containing combination versus 3.6 months in the control arm. Also, higher grade 3 to 4 adverse events were reported in patients treated in the palbociclib arm. Dr. Neeraj Agarwal: Thanks, John. So you are saying that continuing the CDK4/6 inhibitor palbociclib after prior disease progression on palbociclib, even when the primary endocrine therapy has been changed, doesn't seem to be beneficial, therefore, this practice may be discouraged in the clinical setting? Dr. John Sweetenham: Yes, that's correct. Neeraj, I think that's the conclusion from this study. Dr. Neeraj Agarwal: So, John, now let's switch gears and highlight some precision oncology studies.  Dr. John Sweetenham: Well, Abstract 3602, titled “Real World Rates of FDA-Approved Targeted Therapy and Immunotherapy Prescriptions for Metastatic Colorectal Cancer Patients in the VA's National Precision Oncology Program” will be presented by Dr. Alice Nono Djosta. Can you tell us more about this abstract, Neeraj? Dr. Neeraj Agarwal: Well, comprehensive genomic profiling has the potential to guide the administration of FDA-approved biomarker-directed therapies and improve outcomes among patients with metastatic colorectal cancer. So, in this study, Abstract 3602, investigators sought to determine the rates of actionable biomarkers and prescription of associated FDA-approved therapies among veterans in the National Precision Oncology Program. Patients with metastatic colorectal cancer who had undergone comprehensive genomic profiling via tissue or liquid biopsy were included between 2019 and 2022 and had 1 of the following 5 actionable biomarker profiles including: NRAS, KRAS, BRAF wild-type, BRAF V600E mutation, MSI-high, TMB-high, NTRK fusion or rearrangements.  Prescription data for seven FDA-approved biomarker-directed therapies were extracted and rates of comprehensive genomic profiling (CGP)-directed therapy prescriptions were assessed by the investigators. A total of 908 patients with metastatic colorectal cancer underwent comprehensive genomic profiling, with 80% patients having colon adenocarcinoma and 20% with rectal adenocarcinoma. The combined rates of any actionable variants were 47% in patients with colon adenocarcinoma and 45% in patients with rectal adenocarcinoma. After including 424 eligible patients for FDA-approved biomarker therapy, only 70% patients with MSI-high, 48% patients with TMB-high, 38% patients with NRAS, KRAS, and BRAF wild-type, and only 17% of patients with BRAF V600E mutation received FDA-approved CGP-directed therapies.  Dr. John Sweetenham: Very important data, Neeraj. What's the main conclusion of this study? Dr. Neeraj Agarwal: So, in conclusion, this study found that almost 30% of patients with MSI-high metastatic colorectal cancer did not receive effective immune checkpoint inhibitors. And overall, a significant number of eligible patients did not receive FDA-approved biomarker-directed therapies. So, it is crucial that we evaluate the barriers to prescribing comprehensive genomic profiling-directed therapies in our patients with metastatic colorectal cancers.  So, John, let's move on to lung cancer, where the use of single-gene testing is still common in the community practice. Can you please tell us about Abstract 6506, titled “The Impact of Single-Gene Testing on Subsequent Comprehensive Genomic Profiling Success in Community Oncology Practice for Advanced Non–small Cell Lung Cancer”? These are results from a prospective observational reference laboratory testing program and these results will be presented by Dr. Mary Nesline. Dr. John Sweetenham: Yes, definitely. In this study, researchers aim to investigate the impact of prior single-gene testing on comprehensive genomic profiling success and therapeutic opportunities for patients with non–small cell lung cancer in community settings. They included patients who underwent at least 1 single gene testing for guideline recommending genomic variants in non–small cell lung cancer such as BRAF, EGFR, KRAS, MET exon 14 skipping mutations, ALK, RET, and ROS1 rearrangements as well as PD-L1 immunohistochemistry.  And they offered comprehensive genomic profiling either before or after receipt of a negative single gene test. Of 580 patients with non–small cell lung cancer with the comprehensive genomic profiling ordered between 2021 and 2022, around 30% of the patients had at least 1 single-gene testing ordered prior to the comprehensive testing, with a median of 5 prior single-gene tests. Compared to CGP-only cases. CGP per cases with prior negative single gene testing was canceled twice as often at tissue review, had a higher DNA extraction failure, and a lower DNA sequencing success. CGP also identified guideline-recommended variants in genes with no single-gene testing offered during the study period, such as ERBB2 mutations, or NTRK2/3 fusions, as well as variants targeted in ongoing clinical trials in 28% of patients. Dr. Neeraj Agarwal: Very interesting. So John, what is your key takeaway message from this? Dr. John Sweetenham: The main message is that in a community oncology setting, the practice of ordering single gene testing prior to comprehensive genomic profiling for patients with non–small cell lung cancer is common. Prior negative single-gene testing led to a higher rate of CGP test cancellation due to tissue insufficiency and increased CGP DNA extraction failures. The practice of single-gene testing does not align with practice guideline recommendations and may negatively impact the potential benefits of CGP testing for patients with non–small cell lung cancer.  Now, let's move on to another important abstract that our fellow clinicians should hear about. This is Abstract 1534 titled “Real-World Experience of an In-House Dihydropyrimidine Dehydrogenase Genotype Test to Guide Fluoropyrimidine Dosing at a Multi-Site Cancer Hospital” that will be presented by Dr. Jai Patel. Can you tell us more about this abstract, Neeraj? Dr. Neeraj Agarwal: Sure. Fluoropyrimidines, such as 5-fluorouracil and capecitabine, are commonly used to treat solid tumor cancers such as gastrointestinal and breast cancers. We know that severe toxicity occurs in one-third of patients, which delays the timely completion of treatments and result in prolonged hospitalization of these patients. These toxicities may be due in part to genetic variation in the DPYD gene. Five variants are known to have moderate to strong evidence according to the Clinical Pharmacogenetics Implementation Consortium. So, in this observational study, the authors describe the implementation of an in-house DPYD test and its impact on the dosing of these fluoropyrimidines, which include capecitabine and 5-fluorouracil.  From March 2020 to December 2022, 491 patients received DPYD genotyping testing, and 90% of them had gastrointestinal cancers. The median lab turnaround time was only 3 days. Pre-treatment testing was ordered in 80% of patients, and 93% of patients had results before starting cycle 1. Overall, 6% of patients were heterozygous carriers. Fluoropyrimidine dose was reduced, avoided, or discontinued in 90% of these patients. Moreover, in pre-treatment carriers, 90% of patients received an upfront dose reduction, avoidance, or they even declined chemotherapy. Dr. John Sweetenham: Thanks, Neeraj. So what do you think is the key takeaway message here? Dr. Neeraj Agarwal: So, DPYD genotype-guided dosing of fluoropyrimidine, including 5-fluorouracil and capecitabine, is logistically feasible with a rapid turnaround time and can result in treatment dose modifications for most carriers, potentially avoiding or mitigating severe toxicities, especially in those patients who received pre-treatment testing. Dr. John Sweetenham: Thanks again. Now let's transition to studies that focus on disparities in cancer care. Dr. Neeraj Agarwal: Definitely. Let's discuss Abstract 6530, titled “Impact of Free Hospital-Provided Rideshare Service on Radiation Therapy Completion Rates: A Matched Cohort Analysis.” In this study, Dr. Eric Chen and colleagues assess the potential of rideshare services in facilitating timely radiation therapy for patients facing barriers, such as limited transportation, financial constraints, and lack of adequate social support. So the authors analyzed data from about 2,900 patients who underwent radiation therapy and found that 58 of them utilized a free hospital-provided rideshare service.  These free hospital-provided rideshare service utilizers had a lower median age and were more likely to identify as Black or African American compared to those who did not utilize these services. They also had higher socioeconomic disadvantages and traveled shorter distances for treatment. Interestingly, more rideshare utilizers underwent radiation therapy with curative intent, had longer treatment course duration, and a higher number of fractions prescribed. In the matched-cohort analysis, the study found that radiation therapy completion rates were significantly higher for rideshare utilizers compared to non-rideshare utilizers, especially for patients who were undergoing radiation therapy with curative intent.  Dr. John Sweetenham: So what's the key take-home message from this abstract? Dr. Neeraj Agarwal: This study highlights the potential benefit of utilizing hospital-provided free ride-share services, particularly for patients facing barriers to timely treatment. So, using these services were associated with higher radiation therapy completion rates, especially in the curative setting.  So, John, there is another study, Abstract 1606, titled “Trends and Disparities in Oncology Telehealth after the Initial Pandemic Era” that will be presented by Dr. Michael Lee and colleagues. They evaluated whether telehealth utilization continued after the pandemic and if demographic differences in its users persist. So John, please tell us more about this abstract. Dr. John Sweetenham: Yes, the authors conducted a retrospective cohort study in 22 Kaiser Permanente Northern California hematology and oncology clinics between October 1, 2020, and June 1, 2022. The study investigated the use of office, video, and telephone visits, analyzing more than 340,000 hematology oncology visits with MD or DO providers. Of these visits, 25% were in-office, 37% were video visits, and 39% were telephone visits. Monthly telehealth visits peaked in January 2021, representing around 86% of total visits, and decreased to 69% of the total visits by June 2022. Video visits were more common for new appointments, whereas telephone visits were more common for return appointments. Moving to the post-pandemic period, telehealth visits remained popular, with video visits being the most commonly utilized. However, telehealth use varied among demographic populations. Video visits were a significantly higher proportion of all visits among individuals less than 45 years old, primary English speakers, patients with commercial insurance, non-Hispanic Whites and Asians, compared with Hispanic, Whites, and Blacks, and patients living in the deprived neighborhoods. Dr. Neeraj Agarwal: Interesting data, John. So what is the key takeaway message from this abstract? Dr. John Sweetenham: Well, overall, it's encouraging to see that even after the pandemic, telehealth continued to be widely used. However, the concerning issue is that telehealth is less utilized in patients who may need it most. The next step, in my view, will be to work on barriers to access telehealth by underprivileged populations.   And that brings our discussion to a close today. Before we wrap up the podcast, Neeraj, do you have any final thoughts to share? Dr. Neeraj Agarwal: Yes, thanks, John. I would urge our listeners to come and join us at the ASCO Annual Meeting, not only to celebrate these successes but also to help disseminate these cutting-edge data to practitioners and patients across the world. Dr. John Sweetenham: Absolutely. I'd like to thank our listeners for joining us today, and thank you, Neeraj, for sharing your insights with us as well.  You will find links to the abstracts discussed today on the transcripts of this episode. Finally, if you value the insights that you hear on ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts.  Disclaimer:  The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  Find out more about today's speakers: Dr. John Sweetenham Dr. Neeraj Agarwal @neerajaiims Follow ASCO on social media:   @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn   Disclosures: Dr. John Sweetenham: Consulting or Advisory Role: EMA Wellness Dr. Neeraj Agarwal:  Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences   Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas

Dr. John Sweetenham and Dr. Marc Braunstein discuss the role of maintenance therapy in high-risk multiple myeloma, advances in myelodysplastic syndromes in the COMMANDS study, the promise of bispecific antibodies in the pivotal EPCORE NHL-1 in relapsed/refractory large B-cell lymphoma, and improving outcomes for patients with chronic lymphocytic leukemia in the CAPTIVATE trial.  TRANSCRIPT Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham, the associate director for cancer network clinical affairs at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center, and host of the ASCO Daily News Podcast. My guest today is Dr. Marc Braunstein, a hematologist and oncologist at the NYU Perlmutter Cancer Center. Today, we'll be discussing key posters and oral abstracts highlighting advances in hematologic malignancies that will be featured at the 2023 ASCO Annual Meeting.   You'll find our full disclosures in the transcript of this episode, and disclosures of all guests on the ASCO Daily News Podcast are available on our transcripts at asco.org/DNpod.  Dr. John Sweetenham: So, Marc, thanks for returning to us and coming to join us on the podcast today. Dr. Marc Braunstein: Thanks for inviting me back. Dr. John Sweetenham: I'd like to start out with Abstract 8001. This is a study which is addressing the role of maintenance therapy in patients with high-risk multiple myeloma. Could you take us through this study and the key take-home points that you think are the most important ones? Dr. Marc Braunstein: Sure, absolutely. So, the first abstract that we're going to discuss is an oral abstract being presented by Dr. Nooka regarding maintenance therapy in high-risk multiple myeloma patients. Outcomes of patients with multiple myeloma are clearly improving, yet those with high-risk cytogenetic abnormalities, which represent about 10-20% of all multiple myeloma, tend to have poorer survival, and worst among these are those with what's called ultra-high-risk or double-hit multiple myeloma who have more than 1 high-risk cytogenetic abnormality. So, this study looked at maintenance therapy following stem cell transplantation in 26 high-risk patients, about 59% of whom had double hit disease, representing very high-risk disease. This was a phase II study looking at using carfilzomib, pomalidomide, and dexamethasone in high-risk multiple myeloma patients who achieved at least a partial remission following stem cell transplant. There were 26 patients enrolled. The median age was 60. Of note, about 59% of patients were Black, which is important because these patients tend to be historically underrepresented in studies. And what they found was that at study entry, about 24% of patients were in a complete remission or better, and that deepened to 79% while on the study. And the median time to best response was 2 months, which is fairly brisk. With a median follow-up of about 26 months, the 36-month progression-free survival was 63%, and the overall survival was 72%, which is impressive, again in the context of patients who have very high-risk disease. So, although it remains to be determined what the optimal regimen or duration of maintenance should be in multiple myeloma, clearly, combination therapy is effective and should be used in patients who have high-risk or ultra-high-risk multiple myeloma. Dr. John Sweetenham: Great. Thanks, Marc. So, as you say, I mean, clearly the take-home message is around the effectiveness of this type of maintenance therapy. I just have a couple of quick follow-up questions for you. The first of those is, where do you see this going next? I mean, in your opinion, what would be the next logical study with this combination or similar combinations? And then secondly, what do you see on the horizon for those patients with very high-risk myeloma, particularly the double-hit population that you just mentioned? Dr. Marc Braunstein: It's a paradigm in multiple myeloma that combination therapy tends to be more effective as long as we're able to manage the adverse events that come with additional combinations. And we've been able to succeed in that regard with quadruplet regimens, even now that we have monoclonal antibodies that tend to be better tolerated and more targeted in nature. In terms of maintenance therapy, single-agent lenalidomide has been the long-standing agent of use for the majority of patients. But we now understand that the combination of an immunomodulator like lenalidomide and a proteasome inhibitor like bortezomib or carfilzomib is more effective for patients with higher risk disease.   We also have data from various upfront studies of quadruplet regimens, such as the FORTE study, which looked at carfilzomib and lenalidomide maintenance after transplant that shows that we can improve progression-free survival in all comers with multiple myeloma following transplants. So, I think down the road we're going to be looking at more use of combination therapies and maintenance. And as far as for high-risk patients, whether that's going to be using monoclonal antibodies in maintenance or combination proteasome inhibitors and immunomodulators or even other immunotherapies like bispecific antibodies as maintenance in the future remains to be determined, but clearly, for high-risk patients, we should be using combination therapies. Dr. John Sweetenham: Thanks, Marc. Let's change gears a little now and take a look at Abstract 7003, which addresses patients with myelodysplastic syndrome. This study addresses the efficacy and safety results from a study of luspatercept versus epoetin alfa in low-risk myelodysplastic syndrome. I wonder if you could describe this study and the results to us and maybe also for the benefit of our listeners, just mention quickly the mechanism of action of the experimental agent here.  Dr. Marc Braunstein: This is an oral abstract being presented by Dr. Garcia-Manero looking at a phase 3 study, as you mentioned, called the COMMANDS study, and this is looking at an agent called luspatercept in patients with low-risk myelodysplastic syndrome (MDS). So, patients with MDS can have inferior quality of life and survival when they become transfusion dependent. An earlier study called the MEDALIST study, which was published in the New England Journal of Medicine in 2020, randomized low-risk or intermediate-risk patients with MDS who were refractory or unlikely to respond to erythropoietin stimulating agents to either luspatercept, which is an agent that binds to TGF-beta family members and helps stimulate erythropoiesis. Patients were randomized in the MEDALIST study to luspatercept or placebo. And that study showed that luspatercept could improve a degree of anemia and lead to transfusion independence in certain patients. So, the COMMANDS study is a randomized controlled study that randomized 354 patients with low-risk MDS who were transfusion dependent and naive to an erythropoietin stimulating agent to receive either luspatercept or the erythropoietin stimulating agent erythropoietin alfa with the primary endpoint of transfusion independence at some time between 12 to 24 weeks. So, patients were randomized 1:1 to receive either luspatercept or epoetin alfa, and the primary endpoint again was transfusion independence. So, 354 patients were randomized in the study and the median treatment durations were 42 weeks of luspatercept and 27 weeks of epoetin alfa. And transfusion independence occurred in greater quantity in the patients who got luspatercept. For example, in the patients who received luspatercept at 8 weeks, transfusion independence was achieved in 74 versus 51% in the epoetin alfa group. So, in terms of treatment-related adverse events, they were fairly similar between the groups and consistent with the classes -  they were reported in 30% in the luspatercept group and 17% in the erythropoietin group, with no difference in patients who progressed to acute myeloid leukemia.  So, I think when it comes to MDS in low-risk patients, it's really important to preserve their quality of life by limiting their transfusion burden. And I think this study demonstrates that luspatercept continues to be an important part of the management in these low-risk patients. And whether or not you would start a patient with low-risk transfusion-dependent MDS on an erythropoietin stimulating agent or luspatercept is really addressed by this study showing that you can achieve greater rates of improvement in anemia and transfusion independence with luspatercept.  Dr. John Sweetenham: Great. Thanks, Marc. A really interesting study. And I do have one question for you about this study, which I think will make it clear to you that I am an expert neither in myelodysplastic syndrome nor in erythropoiesis. But my question is based on the mechanism of action. Is there any rationale for combining these 2 agents in future studies?  Dr. Marc Braunstein: Yes, it would potentially make sense to use 2 synergistic mechanisms to improve erythropoiesis. We would have to see what the potential for adverse events are. I think epoetin alfa tends to be a fairly low burden in terms of its side effect profile. Luspatercept can have some potentially dose-limiting side effects, such as GI side effects, but you can make dose adjustments to both of these medications. So we may need to find the correct doses of either of them in combination. But from a theoretical standpoint, it makes sense that these could potentially be synergistic, especially in patients who are likely to respond to erythropoietin by having a baseline lower erythropoietin level. Dr. John Sweetenham: Okay, let's move on in another change of gear now. And for the rest of the podcast, we're going to be talking about some studies in lymphoid malignancy, beginning with Abstract 7535, which is a follow-up of the phase 2 CAPTIVATE study which now has significantly extended follow-up from the original report. So Marc, can you walk us through this study and the outcomes to date? Dr. Marc Braunstein: Absolutely. So this is a poster being presented by Dr. Barr and it is looking at CLL, which is a field that is really moving away from chemotherapy for newly diagnosed patients, thanks to the development of novel targeted agents. The CLL14 trial, which was published in the New England Journal of Medicine in 2019, showed that fixed-duration venetoclax plus obinutuzumab improved progression-free survival and rates of negativity of minimal residual disease, or MRD, when compared to chlorambucil and obinutuzumab. So building on the success of that study, combining a monoclonal antibody and a BCL2 inhibitor, the CAPTIVATE study is a phase II study, which examines venetoclax with ibrutinib, the BTK inhibitor, and previously untreated CLL. So it's kind of combining 2of the novel targeted therapies in a fixed duration, similar to what was done in the CLL14 study where patients received 1 year of therapy and then stopped treatment.   So in the CAPTIVATE study, 154 patients were enrolled. This was a phase 2 study that included about 56% of higher-risk patients who had unmutated IGHV, and the median time on the study was 50 months, with a CR rate of 58% at a 4-year follow-up and an overall response rate of 96%, which is quite high, especially considering that more than half of patients had high-risk disease. The progression-free survival was 79% and the overall survival rate was 98% at 4 years. And when they looked at patients who had undetectable minimal residual disease, the 4-year overall survival rate was 100%, which also suggests that MRD can help serve as a predictive marker of longer-term survival. So I think we have to also consider what the side effects are of combining these 2 agents and the most common adverse events were hematologic, which is expected based on what we know about the 2 classes. So I think the implication of the study is that giving 2 oral agents for a fixed period of treatment for 12 cycles is a rational approach that may spare patients indefinite therapy and can lead to positive outcomes, including in patients who have high-risk features with CLL.  Dr. John Sweetenham: Yeah, the other interesting observation that was made in the abstract, which I found to be really encouraging, was the fact that a number of these patients apparently have been re-treated successfully upon progression with ibrutinib again, which seems to be somewhat reassuring as well.  Dr. Marc Braunstein: That's right. There were 4 patients who started re-treatment in the study and perhaps we'll see the outcomes of that small subgroup are at the poster presentation. But I think when we discuss fixed-duration treatment, it also opens the door to potentially re-challenging patients when they relapse. We know that when we stop single-agent BTK inhibitors, which are historically given indefinitely in patients with CLL, those patients who stop, many will relapse, but you can potentially re-challenge them with the BTK inhibitor. So this study with the CAPTIVATE trial gives us some liberty to discontinue therapy, but also considering re-challenging upon relapse.   Dr. John Sweetenham: Yeah, absolutely. Moving on to aggressive B-cell lymphoma, now, the next abstract I'd like to discuss with you is Abstract 7525. I find this one particularly interesting as the continued excitement around CAR T cell therapy for relapsed aggressive lymphoma remains high at the moment. It's intriguing that t cell-engaging antibodies also have been reported, at least, to have remarkable activity in this set of diseases. So can you take us through Abstract 7525 and what they're reporting?  Dr. Marc Braunstein: Absolutely. Bispecific antibodies represent an emerging field in multiple hematologic malignancies, and this is a class of antibodies that bind to both the tumor cell as well as T-cells, and activate T-cell immunity against the tumor cell. So epcoritamab is a bispecific antibody that binds to CD3, which is expressed on T cells, and CD20, which is expressed on B cells. And Thieblemont et al published results in the Journal of Clinical Oncology last year in a phase I/2 study that looked at epcoritamab in patients with diffuse large B cell lymphoma following 2 prior lines of therapy, and this was given subcutaneously until progression of disease. In that study, at a median follow-up of about 11 months, the overall response rate was 63% with 39% complete remissions.   So the EPCORE NHL-1 study, which is being presented at this year's ASCO meeting, is presenting the updated results of that study looking at patients with diffuse large B cell lymphoma that includes a small population as well of patients with high-grade B cell lymphomas and primary mediastinal B cell lymphomas who had at least 2 prior lines of therapy. In this presentation, 157 patients were included in this study, and 61% had primary refractory disease, and actually, 39% had prior CAR T-cell therapy, of whom 75% progressed within 6 months. So these were patients who were not only refractory to treatment but also had prior T-cell therapy.   So at a median follow-up of 20 months, the overall response rate was 63% and the complete response rate was again about 39%, and the median duration of complete remission was 21 months. In terms of overall survival, the median was about 19 months, which is substantial for this group of patients who really wouldn't be expected to respond very well to conventional therapies.   As we know, T-cell-engaging therapies, such as these bispecific antibodies or CAR T-cells have the potential risk for certain immune-related adverse events, including cytokine release syndrome or icons, and a neurologic syndrome related to the therapy. And it's worth noting that the CRS in this study was predominantly low-grade. There were only 3% of patients who had grade III CRS, and 9 patients, or 6% had grade I to II icons. I think that also reflects how we're better managing those side effects and intervening earlier. So I think the results are impressive from the standpoint of the population studied, who were quite refractory to treatment and show relatively high rates of response. In fact, the median overall survival was not reached in the overall population.   So I think what we take away from this abstract is that bispecific antibodies are going to play a vital role in the relapse-refractory setting for large cell lymphoma and may also offer an alternative to patients who aren't necessarily fit for CAR T-cell therapy, which plays a vital role in patients who are both refractory to first-line therapy or relapse-refractory to subsequent disease. So these are very encouraging results, and I'm sure we'll see randomized data as well in the future, further supporting the use of bispecific antibodies like epcoritamab.  Dr. John Sweetenham: Yeah, I agree. Thanks, Marc. I think that's a great summary. And it's particularly exciting to me that the investigators were able to achieve this kind of level of response and progression-free survival with a subcutaneous treatment. It's really quite remarkable and really exciting to see that.  We're going to wind up with our final abstract today, which is looking at the utilization of circulating tumor DNA in, again, in patients with aggressive B cell lymphoma. This is Abstract 7523, so maybe you could walk us through this one, Marc.  Dr. Marc Braunstein: Absolutely. So this is a poster being presented by Dr. Herrera looking at a, I guess you could call it a biomarker in the blood using circulating tumor DNA in patients with newly diagnosed diffuse large B cell lymphoma in the POLARIX study. So the results of the phase 3 POLARIX study were published last year in the New England Journal of Medicine and showed improvement in progression-free survival with the addition of these anti-CD79b antibody polatuzumab to standard R-CHOP chemotherapy compared to R-CHOP alone. And this study actually led to the approval of first-line treatment that includes polatuzumab.   In the abstract being presented by Dr. Herrera, the investigators looked at the value of circulating tumor DNA as a potential marker to serve as a guide for prognosis and predicting longer-term responses, particularly when the blood is cleared of circulating tumor DNA. So the study involved 654 patients who had ctDNA results both at baseline and then with longitudinal assessment, and they used an assay called the CAPP-Seq assay to assess circulating tumor DNA and assess for its clearance. In the study, undetectable circulating tumor DNA was achieved in 57% of patients who got the polatuzumab R-CHP combination and 59% of the patients who got R-CHOP by cycle 5 and then 6% in the polatuzumab group at 67% in the R-CHOP group.  So the rates of circulating tumor DNA clearance were similar between the 2 arms. But what's notable is that patients in the polatuzumab arm who achieved a complete response at the end of treatment plus cleared their circulating tumor DNA had superior progression-free and overall survival compared to patients who achieved a CR but retained circulating tumor DNA in their blood.   And this has implications because it might help gauge, for example, if patients may need additional cycles to clear the circulating tumor DNA, although we still need more data to answer whether that's necessary or not. And it may help serve as a predictive marker for longer-term remission, particularly in patients who perhaps have higher risk factors at baseline. So I don't think this is necessarily ready for primetime to use in clinical practice, but it is intriguing to know that we could finally have a tumor-specific biomarker in the blood to help monitor patients and potentially predict their longer-term remissions.  Dr. John Sweetenham: Thanks, Marc. I agree. Great summary, and obviously there's still something to learn about the kinetics of the response and so on. And also, I suppose it raises the question of whether those patients who still have detectable levels should be switched at the end of therapy to some kind of preemptive second-line therapy. And these are obviously all questions for the future, but it's going to be very interesting to watch this space, I think, and see how this story develops. Dr. Marc Braunstein: Absolutely. And my colleagues in the solid tumor space are already using circulating tumor DNA, for example, in colon cancer, to help with surveillance. So perhaps this could be a tool to use to predict relapse also in patients who are on surveillance after their treatment. But again, as you alluded to, we need more data to address that.  Dr. John Sweetenham: Well, thanks so much, Marc, for sharing your insights with us today on a really interesting set of abstracts coming up at the June meeting. And thanks for joining us on the ASCO Daily News Podcast. Dr. Marc Braunstein: Thank you for inviting me.  Dr. John Sweetenham: And thank you to our listeners for joining us today. You'll find links to the abstracts discussed today in a transcript of this episode. Join us again after the annual meeting for key takeaways on the late-breaking abstracts and other key advances from the ASCO Annual Meeting. And finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers:  Dr. John Sweetenham Dr. Marc Braunstein @docbraunstein   Follow ASCO on social media:  @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn  Disclosures: Dr. John Sweetenham:Consulting or Advisory Role: EMA Wellness Dr. Marc Braunstein:Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb/Celgene, Adaptive Biotechnologies, GlaxoSmithKline, ADC Therapeutics, Janssen Oncology, Abbvie, Guidepoint Global, Epizyme, Sanofi, CTI BioPharma Corp Speakers' Bureau: Janssen OncologyResearch Funding (Institution): Janssen, Celgene/BMS

CardioNerds Amit Goyal, Dr. Colin Blumenthal, Dr. Kelly Arps and Dr. Justice Oranefo discuss mechanical stroke prevention in atrial fibrillation with Dr. Christopher Ellis, cardiac electrophysiology lab director and director of the left atrial appendage closure program at Vanderbilt University. There has been a significant increase in the number of patients undergoing left atrial appendage occlusion (LAAO). This trend is expected to continue with current and upcoming clinical data on this topic. In this episode we dive into the rationale behind LAAO and explore several historical facts. We then proceed to the current state of practice including currently available options, appropriate indications, post op care, and potential complications. Notes were drafted by Dr. Justice Oranefo. Audio editing by CardioNerds Academy Intern, student doctor Chelsea Amo Tweneboah. This CardioNerds Atrial Fibrillation series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Kelly Arps and Dr. Colin Blumenthal. This series is supported by an educational grant from the Bristol Myers Squibb and Pfizer Alliance. All CardioNerds content is planned, produced, and reviewed solely by CardioNerds. We have collaborated with VCU Health to provide CME. Claim free CME here! Disclosures: Dr. Ellis discloses grant or research support from Boston Scientific, Abbott-St Jude, advisor for Atricure and Medtronic. CardioNerds Atrial Fibrillation PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls and Quotes - Atrial Fibrillation: Mechanical Stroke Prevention in Atrial fibrillation Surgical or catheter based left atrial appendage occlusion results in mechanical exclusion of the left atrial appendage, which is the most common source of thrombus leading to embolic events in patients with non-rheumatic atrial fibrillation. Surgical LAAO should be considered in patients with atrial fibrillation and CHA2DS2VASC score ≥ 2 undergoing cardiac surgery for other indications. Endocardial LAAO devices such as WATCHMAN FLX and AMULET are approved for stroke prevention in patients with atrial fibrillation with a CHA2DS2VASC score ≥ 2 and have an appropriate reason to seek a non-drug alternative to anticoagulation therapy. Appropriate patient selection and post-operative anticoagulation and imaging strategy are crucial for prevention and management of complications related to LAAO. Notes - Atrial Fibrillation: Mechanical Stroke Prevention in Atrial fibrillation What are the types of LAAO device? Left atrial appendage occlusion devices can be divided into epicardial closure and endocardial closure. Epicardial techniques/devices include surgical ligation, Atriclip, and Lariat. These techniques require pericardial access (either by open thoracotomy or thoracoscopic access). The goals are complete exclusion and ischemic necrosis of the LAA. LARIAT device Atriclip device Endocardial techniques include WATCHMAN FLX and AMULET devices. These techniques require the use of nitinol-based devices which are delivered into the LAA via a transeptal approach. These devices become endothelialized over time resulting in occlusion of the LAA. AMULET device WATCHMAN FLX Who is the ideal candidate for surgical LAAO? Several studies have evaluated the efficacy of surgical LAA occlusion. The most prominent being the LAOS III trial which randomized 4770 patients with atrial fibrillation and CHA2DS2VASC ≥ 2 undergoing cardiac surgery for other reasons to surgical LAAO vs no LAAO (3,4). The primary outcome of ischemic stroke or systemic embolization occurred in 4.8% of patients in the LAAO group vs 7% of patients in control group over an average ...

Developments in precision medicine have led to a paradigm shift in the management of advanced thyroid cancer. The ESMO Guidelines Committee recently developed a new clinical practice guideline on the use of systemic therapy in this setting. This episode offers guideline insights into the applications recently approved therapies that have been approved by the FDA and/or the EMA, including cabozantinib, selpercatinib, pralsetinib, and entrectinib. It also provides data updates of previously approved therapies and how guidelines have been adapted accordingly. To answer questions on the 2022 ESMO Clinical Practice Guideline update, we have invited Dr. Ahmad Awada to join us. He is Head of the Oncology Medicine Department at Jules Bordet Cancer Institute Brussels, Belgium. Target Audience: Oncologists, pathologists and other HCPs involved in the management of advanced thyroid cancer, with a focus on community practitioners. Learning objectives: After completing this educational activity, learners will be able to: Recall thyroid RET and TRK fusion-positive cancer diagnosis and relevant genomic testing guidelines, and identify ways to adapt the guidelines to local settings Discuss precision medicine and new technologies, including liquid biopsy Review the organization of care and strategies for more efficient care delivery Funding information: This independent educational activity is supported by an educational grant from Eli Lilly. The educational content has been developed by Liberum IME in collaboration with an independent steering committee; Eli Lilly had no influence on the content of this educational activity. Disclosures Dr. Ahmad Awada declares the following financial relationships from the past 24 months: Speaker fees: Amgen, AstraZeneca, Bayer, Daiichi Sankyo, Eisai, Genomic Health, Ipsen, Leo Pharma, Eli Lilly, Merck, MSD, Novartis, Pfizer, and Seattle Genetics. Liberum IME staff, ACHL staff and others involved with the planning, development, and review of the content for this activity have no relevant affiliations or financial relationships to disclose. ACHL requires that the faculty participating in an accredited continuing education activity disclose all affiliations or other financial relationships within 24 months (1) with the manufacturers of any commercial product(s) and/or provider(s) of commercial services discussed in an educational presentation and (2) with any ineligible companies. All relevant financial relationships have been mitigated prior to this activity. This CME/CE activity might describe the off-label, investigational, or experimental use of medications and/or devices that may exceed their FDA-approved labeling. Physicians should consult the current manufacturers' prescribing information for these products. ACHL requires its speakers to disclose that a product is not labeled for the use under discussion. Discussion of Off-Label, Investigational, or Experimental Drug Use: N/A

Dr. Rachna Shroff, chair-elect of the 2023 ASCO GI Cancers Symposium, and guest host Dr. Shaalan Beg discuss new research presented at GI23, including new data from SWOG 1815 in biliary tract cancers, advances in biomarker studies in mCRC such as the PARADIGM trial, and promising updates in ctDNA technology. She also highlights the exciting potential of AI in oncology. TRANSCRIPT Dr. Shaalan Beg:  Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Shaalan Beg, your guest host of the podcast today. I'm an adjunct associate professor at UT Southwestern's Simmons Comprehensive Cancer Center and vice president of Oncology at Science 37. Today we'll be discussing key abstracts and other highlights from the 2023 ASCO Gastrointestinal Cancer Symposium, which celebrated 20 years of transformative care in GI cancers. I'm delighted to welcome Dr. Rachna Shroff, the chair-elect of this milestone meeting. Dr. Shroff is the interim division chief of Hematology Oncology at the University of Arizona Cancer Center. She also serves as the associate dean for Clinical and Translational Research and is the chief of GI Medical Oncology. Our full disclosures are available in the transcript of this episode, and disclosures related to all episodes of the podcast are available on our transcripts at ASCO.org/podcasts. Dr. Shroff, it's great to have you back on the ASCO Daily News podcast. Dr. Rachna Shroff: Thank you so much for having me. I'm so excited to be here. Dr. Shaalan Beg: The ASCO GI Cancers Symposium has been heralded as one of the biggest conferences in the GI cancer space and has occupied this space for the past two decades. Some would say that this year's conference was probably the best GI Cancers Symposium to date. Can you comment on the 20th anniversary milestone and the impact of the symposium on GI cancers? Dr. Rachna Shroff: Absolutely, and that's so great to hear that that's the feedback that you've heard. I have to say GI ASCO is absolutely my favorite meeting of the year, so that is my full disclosure. But I think that this was a tremendous meeting, and I think it was so beautiful that it was also coinciding with the 20th anniversary. It meant so much to us to have Dr. Margaret Tempero open the meeting because she really was the impetus for creating a GI cancer-focused meeting that really brought together multidisciplinary expertise. And so to us, that is what this 20th anniversary represented—20 years of multiple different specialties coming together to discuss how to improve cancer care for patients with gastrointestinal malignancies. And it has been a transformative meeting to see the impact of research presented at this meeting and how it has been implemented over the course of 20 years. And I completely agree that this year in and of itself had some incredible pivotal data that there is no doubt will be practice-changing, and that is absolutely the purpose. I also think that the beauty of this meeting is the networking opportunities for all of us to come out of our individual silos, come together, and discuss cross-cutting care across the spectrum of GI malignancies. And I think that this meeting really did that quite well. Dr. Shaalan Beg: There were many practice-changing studies that made headlines this year, and for me, one of the most anticipated studies was a trial that you led for cholangiocarcinoma and much-anticipated results. The study finished enrollment at a record pace. Can you share your key findings of cholangiocarcinoma? And I'd really like to hear your perspective on cholangiocarcinoma studies. Dr. Rachna Shroff: Yes, it was actually a really big year in the hepatobiliary space, and I was proud to present SWOG 1815, LBA 490, which was the pivotal randomized phase 3 trial looking at gemcitabine, cisplatin, and nab-paclitaxel versus gemcitabine and cisplatin. This was a study that was opened across the entire NCTN and based on a single-arm phase 2 trial that had shown some promising early efficacy of the triplet chemotherapy regimen. As you mentioned, this study accrued 441 patients in two years. And it's really a testament to the fact that the cooperative group mechanism can and should be asking important questions in large, randomized studies and that it is even possible to do in what are historically thought of as, quote-unquote, “rare tumors.” The study was a randomization of two to one to the triplet chemotherapy versus the standard of care for newly diagnosed biliary tract cancer patients. And the primary endpoint was median overall survival. And while the median OS of the triplet regimen was numerically improved at 14 months compared to 12.7 months, this did not meet statistical significance. Other efficacy endpoints, including median progression-free survival and overall response rate, were also numerically improved but not statistically significant, with an overall response rate of 31% with the triplet regimen versus 22%. There were some prespecified stratification factors, including disease site and disease stage, and there may be some interesting signals that bear out of that in terms of perhaps gallbladder cancer and locally advanced patients may be benefiting from the triplet regimen a little bit more, but these are small numbers, and we would really need to explore that in a more rigorous prospective manner. The toxicities were, not surprisingly, there, especially hematologic toxicities. I will say for those of us that use this regimen in practice, we use it a little bit differently than what was done in SWOG 1815, but you can't deny that there were significantly higher grade 3-5 toxicities with anemia neutropenia and thrombocytopenia, though the treatment discontinuation rate did not differ. I think the next steps are really going to be the ongoing biomarker analyses. The study had archival tissue and prospective blood collection and we know that in the space of cholangiocarcinomas and biliary cancers, molecular complexities absolutely play a role in how patients do and how they respond to therapies. So that's going to be an important next step, I think, for this study. Dr. Shaalan Beg: Speaking of biomarkers and an impact on GI cancers, the other malignancy where biomarkers are having a much greater impact than other GI cancers is colon cancer. Another year where we continue to see advances in our understanding of molecularly targeted treatments for colon cancer. What caught your eye? Dr. Rachna Shroff: Well, there were a lot of really interesting studies happening in this space and as a biliary person, one of the first things I got excited about was seeing Abstract 139 that looked at pemigatinib, which is the drug we are very familiar with in cholangiocarcinoma. This was a single-arm phase two study looking at the use of the FGFR inhibitor pemigatinib in metastatic colorectal cancer patients who had FGFR alterations. And so this was a study that was opened through the ACCRU mechanism. It was multicenter with assignment two-stage design and it was specifically for patients with FGF and FGFR-altered metastatic colorectal cancer who had progressed on standard therapies. There was a prespecified interim analysis for futility after 12 evaluable patients and so 14 patients were enrolled in the first stage of the study and evaluated for the primary endpoint of objective response. What was seen and the study was subsequently stopped is that there was really not much efficacy, there was no evidence of safety signals, but this did not seem to be a very active drug in patients with FGFR alterations with no objective response noted. So, the study was stopped with the recognition that perhaps the FGFR translocation or fusion patient population may be something to explore since they did not look at that in this study. The other kind of study that I think is really important was important work of Dr. Raghav and colleagues through SWOG. This was SWOG 1613 Abstract 140. This was the first real study that was investigating targeting HER-2 overexpressed and amplified metastatic colorectal cancer who had RAS wild-type tumors. And it was based on, obviously, some early signals of the effectiveness of HER-2 targeting in metastatic colorectal cancer. And this was a large study looking at pertuzumab and trastuzumab in these patients. They were compared to cetuximab and irinotecan, and the initial plan was for a much larger study. Unfortunately, accrual was really slow so the study was really kind of reformatted and a total of 54 patients were randomized, 26 to the trastuzumab arm and 28 to the CetIri or cetuximab and irinotecan arm. What was seen was that you can absolutely use HER-2 targeting therapies with trastuzumab and pertuzumab in these patients. It was safe and there were some obvious signs of efficacy in terms of overall response rate with an overall response rate of 31% compared to the CetIri arm. Crossover was allowed from the CetIri arm to trastuzumab and pertuzumab. So just that's important to keep in mind when they start to follow out the survival data. But unfortunately, because this study did not accrue, it was stopped early and it's really hard to understand in terms of power calculations the impact of trastuzumab pertuzumab. Of course, we can't talk about this without recognizing that the FDA approval based on the MOUNTAINEER study for tucatinib and trastuzumab came through during GI ASCO. So clearly HER-2 targeting is here to stay in colorectal cancer. Dr. Shaalan Beg: So technology is advancing every year and it's important that we are aware of these advances and how they impact our patients. Probably one of the most exciting technologies in oncology in general is the evolution of ctDNA. And it's been amazing to watch that field unfold as we understand how to use circulating biomarkers for early detection of cancer, for minimal residual disease detection, even as a biomarker of response. What caught your eye when it comes to the use of ctDNA in GI cancers, and how do you see this space develop in the next couple of years? Dr. Rachna Shroff: I completely agree. I think the technology of ctDNA is so incredibly exciting and as somebody who does not actively see and treat colorectal cancer, I'm a little bit envious of my colleagues in that space because the strides that have been made in terms of understanding the utility of ctDNA, especially in colorectal cancer, has just been tremendous and even for the last two to three years. One perfect example of integrating that sort of technology into treatment paradigms is the PARADIGM trial, Abstract 11, which was looking at the concept of hyperselection of patients with RAS wild-type metastatic colorectal cancer who were on the PARADIGM trial which basically looked at frontline FOLFOX with panitumumab versus bevacizumab in patients with RAS wild type left-sided metastatic colorectal cancer. So, you know, the initial data from PARADIGM had demonstrated a longer median overall survival 37.9 months versus 34.3 months, but very smartly, the investigators had also collected baseline plasma ctDNA in the biomarker component of this study and used a custom panel that looked at gene alterations for hyperselection and that included KRAS, NRAS, PTEN, and extracellular domain EGFR mutations HER-2 and MET amplifications, as well as some fusions like ALK, RET, and NTRK. And so out of the 802 patients in the full set, 91% - 733 patients - actually had pretreatment samples for ctDNA, which is really in and of itself, I think, tremendous. And when you break it down, about 28% had at least one gene alteration, and that was across each of those different genes that they were looking at. In the 72% of patients who were defined as hyperselected without any gene alterations, the OS was actually longer with panitumumab versus bev, and that actually was independent of sidedness with hazard ratios that kind of ranged from 0.76 to 0.82. And OS was similar or inferior with panitumumab versus bevacizumab again, regardless of sidedness in patients with any of these gene alterations. And so I think it's a really interesting concept that you can use ctDNA to define negative hyperselection rather than looking at left sided and right sided to really help select patients with frontline therapy in terms of using panitumumab versus bevacizumab. And with the speed with which ctDNA can be obtained, this actually seems like something that could be implemented into clinical practice, which is, I think, really the important component of that. There were a number of other really interesting abstracts. Abstract 5, presented by Dr. Cohen and colleagues, really looked at the kinetics of circulating cell-free DNA and how that kind of relates to minimal residual disease detection rates. And this was in patients with resected stages one through three colorectal cancer. And so, this was a retrospective study, so we have to keep that in mind. And it was multi-institutional in really over 16,000 patients with stages 1 through 3 colorectal cancer. But the complete dataset had about 417 patients and basically the patients' circulating cell-free DNA levels, the total cfDNA, were compared to the ctDNA MRD positivity rates and they looked at very specific time points after surgery. What the authors generally found was that the postoperative cfDNA correlated well with ctDNA positivity and that there was really the ability to see plasma cfDNA levels kind of track and follow with the very specific MRD windows that were being looked at, which really, again, just kind of talks about leveraging this technology in terms of real-world and real-time application and better understanding and informing us of minimal residual disease post what is thought to be curative resection. The last one that I thought was really interesting in relation to ctDNA was actually looking at anal cancer and following ctDNA in patients who were treated with definitive chemoradiation. This was a study that was looking at 31 patients with anal squamous cell carcinoma who were treated with definitive chemo radiation and underwent ctDNA response. The majority of these patients had stage 3 disease and the majority of them received the standard 5-FU Mitomycin with radiation. The patients had ctDNA testing performed in 25 of these patients at baseline and then a smaller number over the course of time, some during chemoradiation. And then they looked again at 30 days post chemoradiation. And at baseline, 88% of patients had detectable ctDNA with those with stage three disease having numerically higher baseline ctDNA levels. And basically what they found was that over the course of treatment, ctDNA levels decreased among the patients with detectable ctDNA. And then ctDNA that tested during chemo radiation showed a drop in decline and were going into molecular remission at a time point in which it was subsequently confirmed that they had a clinical complete response. So, the suggestion here is that the time to molecular ctDNA remission was significantly shorter than being able to see that clinical complete response, which suggests that using surveillance ctDNA monitoring could be an earlier response assessment for patients with anal squamous cell carcinoma who are undergoing definitive therapy. Now, obviously this needs to be confirmed in a larger manner, but again, really suggests that we could be understanding how we're doing with treatment in more of a real-time fashion, which I just think is incredible for those of us who are making sure that we are doing and taking the right approaches for these patients. Dr. Shaalan Beg: One of the major transformative announcements that took place only a couple of months before the GI Cancer Symposium was the announcement of ChatGPT. And we heard a lot of discussion on how it can be used for improving cancer care, improving drug development, and in general, artificial intelligence and machine learning. We've been hearing these buzzwords for such a long time, to the point that a lot of people are probably just filtering it out and then this tool comes up and it makes it real. And we're seeing different people apply these technologies in different ways. But there is tremendous potential in how this technology can improve clinical trials, drug development, and early diagnosis. And luckily, we had already secured a keynote speaker, Dr. Matthew Lundgren from Nuance Communications, and he was invited to talk about artificial intelligence, machine learning, and how it applies to cancer care. I'm really curious to hear what your highlights were from his address and how you see this impacting your day-to-day, or just the ecosystem of which we're all part of. Dr. Rachna Shroff: Yeah, I will say that his keynote was really one of the highlights of the entire meeting for me. And that is coming from somebody who doesn't really know– I know who I'm speaking to, but somebody who does not truly understand the way AI is moving. And so, I was joking with him that it was like AI 101. And I really, really appreciated the way he was able to kind of speak to a crowd that he doesn't normally speak to and help us really understand the way in which artificial intelligence can be integrated into healthcare, and specifically oncology. To me, I think what were the most salient takeaways from his address was really about how this is just a rapidly evolving field and we need to be a little bit ahead of the eight ball when it comes to thinking how we can smartly leverage artificial intelligence like you mentioned, to improve our clinical research efforts, to improve access, and to improve fully integrating AI into our EMR, so that we can really leverage that technology and ensure that we are capturing every potential patient for a clinical trial and be smarter about how we're even approaching things. I mean, I loved him talking about the prior authorizations and that sort of thing, and the ways in which we can decrease the burden on health care providers and really let us focus on the areas that we need to focus on. The one thing that I thought was a really important point, though, and I think a number of people asked him, was about how using this technology has the potential to create more gaps and disparities and how can we be smart to ensure that we don't broaden those gaps. And I think that is a really important point that we all need to think about because we know that especially when we think through clinical trials, there's already underrepresentation of certain populations and certain geographic regions. And so, I think that was a really important takeaway for me is how can we make sure that we work and partner with those who are creating these technologies to ensure that we aren't taking two steps forward and four steps back. Dr. Shaalan Beg: It really calls into question how we define productivity and what our value in the entire delivery system really is. And I think from people who are in middle school or high school to people who are in college and even folks who are in the field as you and I are, it's forcing us to rethink what we bring to the table in a way that we've never been challenged to ask that question ever before. Dr. Rachna Shroff: Absolutely. Dr. Shaalan Beg: So, thank you very much, Dr. Shroff. This was wonderful. Thank you for sharing your insights with us today. And we thank you and Dr. George Chang, the chair of the ASCO GI Cancers Symposium, and everyone who worked so hard to develop a robust program this year.  Dr. Rachna Shroff: Thank you. It was so wonderful to be able to speak about it. And thank you to all of the attendees for making it such a memorable meeting. Dr. Shaalan Beg: And thank you to all our listeners for your time today. You'll find links to the abstracts discussed today on the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News podcast, please take a moment to rate, review, and subscribe wherever you get your podcast. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experiences, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers: Dr. Shaalan Beg @ShaalanBeg Dr. Rachna Shroff @rachnatshroff Follow ASCO on social media:  @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn  Disclosures: Dr. Shaalan Beg: Employment: Science 37 Consulting or Advisory Role: Ipsen, Array BioPharma, AstraZeneca/MedImmune, Cancer Commons, Legend Biotech, Foundation Medicine Research Funding (Inst.): Bristol-Myers Squibb, AstraZeneca/MedImmune, Merck Serono, Five Prime Therapeutics, MedImmune, Genentech, Immunesensor, Tolero Pharmaceuticals Dr. Rachna Shroff: Consulting or Advisory Role: Exelixis, Merck, QED Therapeutics, Incyte, Astra Zeneca, Taiho Pharmaceutical, Boehringer Ingelheim, SERVIER, Genentech, Basilea Research Funding: Pieris Pharmaceuticals, Taiho Pharmaceutical, Merck, Exelixis, QED Therapeutics, Rafael Pharmaceuticals, Bristol-Myers Squibb, Bayer, Immunovaccine, Seagen, Novocure, Nucana, Loxo/Lilly, Faeth Therapeutics        

In this introductory episode of the JCO Precision Oncology Conversations podcast, host Dr. Abdul Rafeh Naqash, MD, from the University of Oklahoma Stephenson Cancer Center, speaks with JCO Precision Oncology's founding Editor in Chief, Dr. James Ford, MD, of Stanford University. Dr. Naqash and Dr. Ford discuss how JCO Precision Oncology (JCO PO) started as a journal and how it has progressed since its launch in 2017. Dr. Ford dives into numerous JCO PO areas of interest, including liquid biopsy, genomics, biostatistics, and JCO PO-offered opportunities like the editorial fellowship program. GUEST BIO Dr. James Ford, MD, founding Editor in Chief of JCO Precision Oncology, received his MD degree from Yale University School of Medicine. He is currently Professor of Medicine (Oncology) and Genetics at Stanford University, and Director of the Stanford Cancer Genetics Clinic and the Cancer Genomics Program at the Stanford University Medical Center." TRANSCRIPT Dr. Abdul Rafeh Naqash: Welcome to ASCO's JCO Precision Oncology Conversations, where we bring you the highlights and overview of precision oncology. Episodes will feature engaging conversations with authors of clinically relevant and highly significant articles in JCO Precision Oncology. These articles can be accessed at ascopubs.org/Journal/PO. Hi, my name is Dr. Abdul Rafeh Naqash and you are listening to the JCO Precision Oncology Conversations podcast. Today, I will be talking with Dr. James Ford, about JCO Precision Oncology. Dr. Ford is the editor-in-chief for JCO Precision Oncology. It's great to have you here today, Dr. Ford. Dr. James Ford: Thanks, Rafeh, so much for hosting me and for running this podcast series. I think it's going to be great for the journal and for our audience. Dr. Abdul Rafeh Naqash: Thank you so much, Dr. Ford. For the sake of our audience, could you introduce yourself with respect to your interest in medicine, oncology, and precision medicine specifically? Dr. James Ford: Sure! Well, I'm a physician-scientist, I trained at Stanford in medical oncology in genetics, and have spent my whole career here over 30 years. So, currently, I'm a professor of medicine in the division of oncology and genetics. I have focused my scholarly activities on cancer genetics and run a lab that's worked mostly in the field of DNA repair, and of course, this has evolved through the era of discovering and taking advantage of the fact that DNA damage response genes have turned out to be excellent targets for therapy in cancer. And so, this really combined my interest in the genetics of cancer and in targeting those biomarkers for therapy, which really has become the field of precision oncology. So, I run the Molecular Tumor Board here at Stanford and our Hereditary Cancer Genetics Program. So, that's really led to my interest in understanding both hereditary and somatic cancer genetics, and how we can use new targeted therapies to take advantage of understanding those biomarkers. Dr. Abdul Rafeh Naqash: Thank you so much for letting our audience know about all the work that you've done. You've definitely have been a leader in this field of cancer genomics and precision medicine. Talking about the intersection of where your interests met with starting JCO Precision Oncology, could you tell us since this is one of the sentinel episodes for our podcast series, could you elaborate on how you decided to start JCO Precision Oncology as a journal? And what was your vision of how you would shape the journal as it continued to progress over the subsequent years? Dr. James Ford: Sure! Well, the credit really goes to ASCO for the vision to start this journal about 6 or 7 years ago. ASCO decided to start adding some sister journals to its very successful flagship journal, the Journal of Clinical Oncology. And one of those, it was decided that an area, burgeoning area of interest that would be useful to our community is around precision oncology. And so, they launched a search release for a founding editor for what was named then JCO Precision Oncology, and I was fortunate enough to be chosen to be that founding editor. So, the journal started publishing just 5 years ago, right about now, this is our 5th anniversary, really, with the goal of focusing on research and reports, particularly around the clinical use of profiling tumors in individuals, as a way to advance therapies as a general scope. So, this was to add to the value that JCO, the parent journal, already has in thinking about this field that's taking advantage of n-of-1 study or of sometimes small series of studies because of the rarity of some of these genomic changes. So, scientific advances that we can take advantage of clinically, that perhaps don't fit into the traditional large phase three randomized study that reached the level of JCO, or some other journals. And I think we've seen since starting that this really has addressed an excellent niche in the field and allowed an area to publish really excellent research that doesn't always fit into some of the other journals. So, I guess the first step really then 5 years ago, 5-6 years ago, when we started this journal, was really with the truly excellent staff at ASCO and JCO, which helped launch this journal to put together our initial associate editors and board of editors, which I think truly has been one of the best parts of this whole general experience. We have the leaders in the younger generation of cancer therapy researchers and oncologists focused on precision oncology, all gathered together in this journal. And it's actually one of the most fun things about doing this is working with this great group. Of course, we've been adding to that over the years, but really, our initial core group has stayed with us. And together with the great staff and all the reviewers that have helped with this really started to put a focus on the sorts of papers and the kind of areas that it's really useful for us to publish them. Dr. Abdul Rafeh Naqash: Definitely, as you mentioned, Dr. Ford, the success of a journal, like JCO PO involves a large team that works behind the scene, including yourself and many others, as well as the reviewers who do their due diligence in helping us get the right content out there. So, you mentioned about your interest in DNA damage and you mentioned about your interest in cancer genomics. Based on how you have seen this whole field evolve, what is your understanding of how we can incorporate more and more precision medicine from an early therapeutics' standpoint and also from a standard of care standpoint? Where do you see all that going from a testing standpoint, as well as a clinical application standpoint? Dr. James Ford: Well, I think one of the really interesting aspects of the tenure of this journal has been moving from what still is and largely was a research-based approach to cancer therapeutics using genomic and other types of molecular profiling of tumors to try to select therapies in the best way for individual patients to taking that to hopefully becoming standard of care, a better understanding how to apply that to certain individual patients, as well as have groups of patients, how to best use genomic biomarkers, and how to best encourage the development of new targeted cancer therapies for that type of use. So, I think an exciting aspect has been also profiling new clinical trial methods, and new biostatistical ways of looking at this kind of data that can't always be done in traditional large randomized trials – how to advance the field clinically, based on really the incredible technological underpinnings of the field. And so, that's required, I think, some novel and different ways of looking at and publishing data. So, of course, we are publishing original reports of excellent science, often based on preclinical findings, but always trying to find those that certainly have applications to the clinic and preferably have been tried in the clinic and shown advancements that we can take advantage of, but also, I think, importantly, has been publishing case reports, and other ways of highlighting smaller successes in the field that can lead to further larger clinical investigations. And as you know, it's hard to find journals and places where that can be published. Of course, we're quite restrictive in the kind of case reports we publish, we want to do those that have really high educational value or high predictive value for future clinical use. But I think precision oncology is one area of medicine, where looking at individual cases can be very revealing for future clinical benefit. Another thing we're doing and we founded was a series of what we call molecular tumor boards, and that really is just a description of a case or cases that are written from a Molecular Tumor Board group and describes the process of using very complicated genomic test reports and expertise from a number of physicians and scientists in interpreting that to best try to advance the therapy for a patient or group of patients. And I think that helps show to clinicians the value of a molecular tumor board or this kind of approach to analyzing both the lab-based genomic data and clinical experience and use of molecular pathology and pathologist experience, to synthesize these kinds of cases, and I think these have been very revealing as well and useful to the literature. Dr. Abdul Rafeh Naqash: Absolutely! I completely agree with you. And based on everything that you mentioned JCO Precision Oncology has definitely had a lot of significant and important submissions that have come out, and as our viewers might know, we have our most recent impact factor which is close to 5.5. So, congratulations to you Dr. Ford, and I guess the rest of the team that worked behind the scene for accomplishing this. Do you have any additional thoughts on anything that the listeners should know on the kind of content that you'd be interested in getting submissions for over the next 6 months to a year so that we have an understanding from the listeners of what kind of content is most acceptable like you mentioned earlier? Dr. James Ford: Sure! Well, as I said, we publish a number of types of articles, obviously, original scholarly reports and investigations, case reports, Molecular Tumor Board discussions, editorials, and commentaries on papers in our journal or others or areas in the field that are interesting. I think we have a healthy dialogue happening in the journal with discussions and responses from authors regarding papers we publish. This is an online journal and so we really try to publish in real-time and have an interactive forum for that. So, of course, anyone is welcome to submit ideas or commentaries on areas in the field that we think are important or should be advanced. So, we serve as a forum for that discussion as well as publishing traditional articles. I would say something that we've tried to focus on and we'll continue to do so is every year having one or several particular areas of interest that we're recruiting articles or commentaries, review articles about. Over the last couple of years, for example, we had a series very much focused on liquid biopsies and how the use of circulating tumor DNA is really revolutionizing precision oncology. We had a wonderful set of articles from our biostats editor, Ying Lu, on new biostatistical approaches to clinical trials in the area of precision oncology, thinking about the particular needs in that area. I think in the next year or so, we are launching a series right now on the use of genomic profiling, molecular profiling in earlier-stage cancer, and how to use that information for choosing or defining the correct adjuvant therapy in early cancers or using it before the metastatic setting, trying to move the process up. Is it appropriate? Where should it be used? How best to use that? It is quite an open area that I think we're going to make great advances on in the next few years. I think an area of great interest is how to think about combining targeted therapies in a precision oncology approach. How do you test preclinically? And then, of course, clinically, multiple agents together to take advantage of genomic biomarkers to advance therapies and how to test that in the clinic which is, of course, a great challenge. How to rationally pick those agents that we think might provide synergy. Of course, an area of great interest for everybody is thoughts around diversity, equity, and inclusion in clinical medicine in general, but for us, specifically, in best understanding genetics and genomics of diverse populations, how to be most inclusive in our clinical trial process, and testing of these approaches. And I think we've had a number of very thoughtful articles in this space and encourage more in this area as well. Dr. Abdul Rafeh Naqash: Thank you so much. Those are all amazing things that the journal is trying to implement. All those topics that you mentioned are extremely important and very interesting as far as precision medicine goes. Shifting gears a little bit. Dr. Ford, could you tell us about the JCO Precision Oncology Editorial Fellowship? As you know, I am a product of that editorial fellowship, where I was paired with Dr. Rodrigo Dienstmann, and it was an amazing experience. For the sake of our listeners, early career investigators, fellows, could you tell us a little bit about what this fellowship is and how that integrates into how we are trying to shape JCO Precision Oncology and the next generation of precision medicine specialists? Dr. James Ford: Sure! Well, I think this has been a really exciting and fun area for the journal. And in fact, for all the ASCO journals. ASCO instituted a fellowship program several years ago, in which mostly senior fellows, and junior faculty members in related fields, apply to work with one of the journals over the course of a year. And so, for the past several years, we've been fortunate enough to have two editorial fellows assigned to JCO PO that have worked with our associated editors throughout the process, really to learn how to not only review and manage manuscript submissions, but to best think about some of the issues we've been talking about like, how to show tape the direction of a journal, how to think about what are the most important areas in a field that we want to highlight, and hopefully can support. And it's been a great experience. We the editors have loved working with the fellows, really all of the fellows have gone on and continued in this field in academics across the country, and across the world, and a number have gone on to continue working with the journal like you, Rafeh. It's been terrific, as our audience knows. And you mentioned you were a fellow and now joined the journal as part of the editorial staff to run this whole social media program. And a number of our other fellows have joined the editorial board and continue to work with us and to really contribute to the field. So, I think that program has not only been really helpful to the folks who participated in it but to the field and to our journal in developing new talent and recruiting them to the field, so, very successful! We've even taken another step in the journals towards this and the board of editors themselves are serving as mentors to other folks and mostly fellows in medical oncology and related fields, simply to learn how to become better reviewers of papers, and go through that process with a little guidance from the editorial group. And of course, this really helps us to deepen our pool of expert reviewers and referees for journals. So, I think this process has been iterative and very beneficial to the journal. Dr. Abdul Rafeh Naqash: Definitely, I totally connected with that, Dr. Ford, as you mentioned, I was a JCO PO editorial fellow, worked with Dr. Dienstmann and yourself, and it led to subsequent interactions and roles within JCO PO, which has been amazing. I would definitely encourage all the listeners, whoever is interested in applying, if they fit the eligibility criteria to definitely apply, to the ASCO Editorial Fellowship, especially JCO Precision Oncology, given my bias towards the journal. It was amazing talking to you, Dr. Ford. Do you have any closing thoughts on what our listeners should be expecting as far as the journal or any other suggestions that you have for potential submissions out there, any other thoughts that you would like to share with our audience? Dr. James Ford: Well, thanks, Rafeh, for having me and for conducting this interview. It's been a pleasure to talk about the journal. I would conclude by saying that this has been a great experience for me, and I think our whole editorial group, to start and to develop this journal, and really see how both it can grow itself and how I think it contributes to the growth of the field and serve as a nidus for our field in exchanging information and developing new ideas and thoughts that can benefit our patients. So, I just would like to thank all of our group, our reviewers, and certainly the authors and folks that have submitted articles and ideas to the journal. I think it's making a difference. And I think the field, in general, is at a very exciting point and is making a difference for patient care, and will continue to do so with new technologies and new therapies and new ways to incorporate those. So, I think we've shown that this has been a useful journal for the field and I think I'm very excited about where things are going to go. Dr. Abdul Rafeh Naqash: Thank you so much. I completely echo your thoughts. I would like to encourage the listeners to stay tuned for subsequent author conversations, and other interactive conversations that we'll have on our JCO Precision Oncology Conversations podcast, subsequently. Thank you so much for joining us today, Dr. Ford. Dr. James Ford: Thank you. Dr. Abdul Rafeh Naqash: Thank you for listening to JCO Precision Oncology Conversations. You can find all our shows, including this one, at asco.org/podcasts, or wherever you get your podcasts. To stay up to date, be sure to follow and share JCO PO content on Twitter. The Twitter handle is @JCOPO_ASCO. All JCO PO articles and series can be found at ascopubs.org/Journal/PO.   The purpose of this podcast is to educate and inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement. Disclosures Dr. James Ford's institution receives research funding from Genentech, AstraZeneca, Puma Biotechnology, Pfizer, Merus, Bayer, and Incyte.      

Professor Piotr Rutkowski, of the Maria-Sklodowska-Curie National Research Institute, discusses how Poland is managing the influx of 5 million Ukrainian refugees since the war began and tells host Dr. John Sweetenham, of the UT Southwestern Harold C. Simmons Comprehensive Cancer Center, about the future health needs of Ukrainian refugees with cancer. TRANSCRIPT  Dr. John Sweetenham: Hello. I'm Dr. John Sweetenham, the associate director for Clinical Affairs at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center and host of the ASCO Daily News podcast. My guest today is Professor Piotr Rutkowski, who leads the department of Soft Tissue and Bone Sarcoma and Melanoma at the Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Poland. Prof. Rutkowski is also the deputy director for the National Oncological Strategy and Clinical Trials, and serves as president of the Polish Oncological Society. Prof. Rutkowski spoke with us earlier this year as millions of people were fleeing the war in Ukraine, and he described the really remarkable response from both the Polish government and his institution to this crisis. He's back on the podcast today to tell us about cancer care for Ukrainian refugees 5 months into the conflict, and how health systems are coping with the influx of millions of refugees. He will also share his insights on the kind of support that will be needed long-term to care for these patients in the future. Our full disclosures are available in the show notes and disclosures relating to all guests on the podcast can be found on our transcripts at asco.org/podcasts. Professor Rutkowski, thank you for being on the podcast today. It's been about 4 months since we last spoke. How are you doing? Dr. Piotr Rutkowski: I'm very privileged that we can speak again. I'm talking probably on behalf of many Polish physicians and citizens involved with this dramatic situation of war in Ukraine and helping our patients and citizens from Ukraine. And I feel okay, but of course, the situation is still dramatic, and we don't know what will happen during the next months. What we can tell, first, is what has been changed for these last 4 months, it is the number. So as of now, almost 5 million people from Ukraine crossed the border between Ukraine and Poland. And we can estimate that about 3 million refugees stay temporary or maybe even permanently in our country. This is a completely new situation because it means that it's about 10% of our citizens now. And what didn't change but still the cancer care for Ukrainian patients is the extension of regular cancer care within our national oncology network and our national health fund with this Polish insurance system. And this is the same for patients in Poland. And so all refugees from Ukraine are entitled to receive the same care as citizens of Poland. Still, this extraordinary legislation, which was adopted by the Polish parliament, covers all the refugees of war, social security, and health insurance. And we have a better situation because all comprehensive cancer centers or major cancer centers organize the help with a hotline, not only on the level of the whole country but also on the center level in the Ukrainian language. And the majority of these centers have staff speaking the Ukrainian language. Moreover, what I can say as a president of Polish Oncological Society, recently, with the help of an educational grant, we bought electronic translators for major oncological cancer centers. So they can help in the situation, like in the emergency situation, when we have access to live talk. So they can be used in that situation. And in my opinion, it is very, very helpful. So this is the current situation. And of course, I will present further the structure of oncological patients from Ukraine in Poland now and what's been done. Dr. John Sweetenham: Thank you. It's really quite extraordinary to grasp that your patient population almost overnight increased by 10%. That's just quite extraordinary. What aspects of the cancer care would you say are working well at the moment and what are your greatest remaining challenges with this population as of now? Dr. Piotr Rutkowski: First, with this challenge for the pediatric cancer population, and about 1,000 children with cancer were evacuated from Ukraine. They were transported to the Ukrainian hub near Lviv in western Ukraine and thereafter to Polish hub. And with help of many nongovernmental organizations (NGOs) and many organizations, many hospitals from Europe but also U.S. and Canada, many institutions helped within this operation to transfer after triage the pediatric, so children with cancer, to Polish, German, and U.S. physicians. So more than 1,000 children were transferred to these different hospitals around the world—so Europe, the USA, and Canada. But of course, when we look at specific other issues with Ukraine refugees with cancer, first we have a very extraordinary situation and demography because the majority are women with children and only a very small percentage of males, mostly in older age. So when we looked at the cost of hospital admission of patients from Ukraine until May, the signs and symptoms were not in abnormal laboratory tests, or not otherwise classified. So generally, [these were] different conditions, mostly internal conditions. The second one was obstetric gynecology, so pregnancy, childbirth, etc. And the third in the rank were neoplastic diseases. I looked also carefully how it looks on the level of our institution because Maria Sklodowska-Curie National Research Institution is the largest oncological center in Poland. And we have the central part in Warsaw, but also we have 2 branches in Poland. So when we looked at the populations, all together, we had about 1,000 visits with new patients in our institutions. And number 1 was breast cancer. And second were gastrointestinal, and thereafter gynecology. And the fourth in the rank was melanoma and also soft tissue tumors or cancers probably related to the younger population. But melanoma was also relatively frequent. But number 1 was breast and reconstructive in all our branches. And of course, the distribution of patients is also different. In the whole of Poland, the largest numbers are in our region because probably because Warsaw is the largest city in Poland. So they have a lot of relatives or colleagues. So about 20% of patients from Ukraine are concentrated in our region, but more than 10% are also near Katowice or Gliwice. So it's Silesia and also near Krakow. So this central and southeastern part of Poland have the majority of Ukrainian patients now. However, of course, some of the patients were also transferred to other parts of Poland. But as I said, in some of the departments, more than 10% of patients are now from Ukraine, especially in breast cancer units and also gynecological units. When I look in the department which I'm chairing, department of soft tissue, bone sarcoma, and melanoma, we have mostly patients from Ukraine involved in the treatment of advanced melanoma, some with earlier stages, and some patients with sarcoma, especially if they were contacted by physicians from Ukraine specifically for this type of disease. But generally, the state of disease is a little bit more advanced. So, many of these patients are receiving neoadjuvant therapy in breast cancer or they are going directly to treatment of stage IV disease with modern drugs like immunotherapy or targeted therapy for melanoma. This is also the real situation. One of my points I want to mention is, if the access to the cancer care, regular cancer care probably is good for patients, but the problem with communication exists, and still I think that patients or citizens from Ukraine do not participate too much in prevention programs because the participation in mammography, cytology for cervical cancer and other screening programs are at very low levels. So, of course, it's a new situation for these people. But still, probably it will be one of the points for which we have to undertake some strategies. Because we do not know how to get information on if they will be staying longer in our country what we can anticipate for next months and even years. So this can be problematic because it means that we'll have more and more advanced stages of disease. Dr. John Sweetenham: It's very interesting, and of course not surprising, that you have this very skewed demographic of predominantly female patients. I wonder whether you have any insights into whether the—maybe resistance to screening is the wrong word—but the reluctance to be screened? Is that do you think, a reflection of screening services in Ukraine? Or do you think it relates more to the current stresses and priorities that these patients face? Dr. Piotr Rutkowski: I think whether it's first for our colleagues from Ukraine, it's a new situation, and they still are not in a normal life. So I agree that first, of course, the participation in the screening programs in Ukraine is on the lower level, but still, maybe the people do not consider staying here, staying at home, of course, and staying in their own country. So they are a little bit in between of normal life and living as refugees only. So they did not start all normal activities. And of course, the information about the screening programs, about the normally functioning health care, it's also probably a little bit more difficult for them because they may not understand all the details of our health care. So I think that it is one of the points which we have to think about for new strategical enterprises in the coming months. So as I mentioned, for normal access to health care, I do not foresee now that it's problematic. Of course, it can be problematic if we'll have a shortage of our people. But still, we can manage this on a regular level. But as I mentioned, when I talked to our colleagues from the department of prevention, the percentage of the people who are coming for screening programs is very low as compared to the total number of refugees. Dr. John Sweetenham: You mentioned that the future for many of the Ukrainian refugees is uncertain at the moment. Now that the heaviest fighting appears to be concentrated on the east of the country, are you seeing any signs that Ukrainian patients will be able to go home for their treatments at any point in the near future? Dr. Piotr Rutkowski: Yes, I think so. Some of the refugees even started to come back home to Western Ukraine, especially when they felt that it was a little bit safer. But as we know, still the situation on the front and the plans of the Russian invaders are not predictable. So we cannot say how even we can behave in this situation. So, for example, in my hospital, we have psychologists from Ukraine who first escaped from Donbas to Kharkiv. And when Kharkiv started to be shelled by bombs, they escaped to Poland. So it's sometimes really dramatic fates for these people. So, of course, the movements between the border are relatively high because some of the people are trying to come back because they feel more comfortable in their homeland, in the country where they can all speak one language, but others they feel they've started to adapt to in living in Poland and we have more and more patients who are accompanied by people speaking Polish. So they started to try to live more normally in our country. I also noticed that we have some patients from Ukraine in the clinical trials. Of course, we also adapted the informed consent and some information sheets into the Ukrainian language. So Ukrainian patients interested in taking part in clinical trials are also included based on normal inclusion criteria. This is also important that we can propose this to patients from Ukraine because if they want to stay longer so they can get extra treatment within the frame of clinical trials. What is also interesting with our National Science Center is that it started to support researchers who are fleeing from war. And they prepared the special funding scheme for researchers from Ukraine to encourage the grant winners to employ researchers from Ukraine on ongoing projects. So there are many specific actions to adapt the citizens of Ukraine in Poland, and of course allow them to undertake normal work. We also allowed for specific temporary work in health care for physicians and nurses. And as it was announced recently by the Polish Minister of Health, more than 2,000 physicians from Ukraine decided to work in the Polish health system. So this is what we can do now. And probably we can do follow-up in half a year again. We'll see what will happen. Dr. John Sweetenham: I thank your responsiveness and that view of government. So this situation has been really remarkable and also remarkably quick. And as you've already pointed out, these patients are going to have needs for many months and many years to come. And you've touched on some of those, specifically the needs around cancer screening. Do you have any other insights into what you think the most pressing future needs for these refugees will be? And then what support your health system, which is presumably already overstretched, what additional support will it need to cope with the ongoing demands and needs of this population? Dr. Piotr Rutkowski: We really appreciate the help from the international community with material for our Ukrainian patients. Probably the next step will be a specific maybe European Union (EU) fund for a health care system which is affected now by numbers of patients from Ukraine, because, of course, we are doing this with our internal Polish funds. But I don't know how it would affect the next year with regular health service in Poland. So this is one of the points. The second point, of course, which we are always afraid of is the situation with the staff shortage for regular health care because Poland, generally in our part of Europe, we can see the shortage of nurses and educated oncological physicians. This is what we included in our national oncological strategy. However, we didn't anticipate it would have such an extraordinary situation which we have to face now. So these points can be one of the problems which can be raised next month. Dr. John Sweetenham: And so you you've indicated the potential support from the EU and other international agencies. I wonder if we could take that question a little bit further to the international oncology community, including organizations like ASCO, the European Cancer Organization (ECO), the American Cancer Society, and others, who've been collaborating to support Ukrainian patients and the oncology community in Poland and in the region. How do you think the international oncology community can continue to respond and help in the coming months and years? Dr. Piotr Rutkowski: It seems that it's a very continuous effort. So we have regular meetings between the national representatives, ECO, as you mentioned, ASCO, and also some NGOs to discuss the hottest problems with the situation in Europe and also how we can find solutions. Colleagues from Ukraine are also asking us about these specific issues like access to radiation therapy and the possibility to transfer the patients because the equipment is not working perfectly in the whole of Ukraine. This effort is very, very important. I feel that it will be a very excellent platform for next month, maybe for next year. I think that it's extraordinary because it was organized very fast, and it was not temporary, but it seems that it will be continuous for a long time. As I mentioned in this platform, we can exchange some materials, and some information very quickly and in an efficient way. I would like to thank you, ASCO, and ECO for the organization of this platform. Dr. John Sweetenham: Well, Professor Rutkowski, I want to thank you again for taking the time to join us for a follow-up discussion regarding the situation in your country with respect to Ukraine, and express, once again, our respect and admiration for the way that you and your colleagues and your country have responded to the crisis. It's been a real pleasure having you on the podcast today. So thank you for joining. Dr. Piotr Rutkowski: Thank you very much. Goodbye. Dr. John Sweetenham: And thank you to our listeners for your time today. If you're enjoying the content on the ASCO Daily News podcast, please take a moment to rate and review us wherever you get your podcasts.   Disclosures: Dr. John Sweetenham: Consulting or Advisory Role: EMA Wellness Dr. Piotr Rutkowski: Honoraria: Bristol-Myers Squibb, MSD, Novartis, Roche, Pfizer, Pierre Fabre, Sanofi, and Merck Consulting or Advisory Role: Novartis, Blueprint Medicines, Bristol-Myers Squibb, Pierre Fabre, MSD, Amgen Speakers' Bureau: Pfizer, Novartis, Pierre Fabre Research Funding (institution): Novartis, Roche, Bristol-Myers Squibb Travel, Accommodations, Expenses: Orphan Europe, Pierre Fabre Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.    

Host Dr. John Sweetenham, of the UT Southwestern's Harold C. Simmons Comprehensive Cancer Center, and Dr. Bridgette Thom, of the Memorial Sloan Kettering Cancer Center, discuss a novel intervention to address financial toxicity and social need using the Electronic Medical Record.   TRANSCRIPT Dr. John Sweetenham: Hello. I'm Dr. John Sweetenham, the associate director for clinical affairs at UT Southwestern Harold C. Simmons Comprehensive Cancer Center and host of the ASCO Daily News podcast. My guest today is Dr. Bridgette Thom, a researcher at Memorial Sloan Kettering (MSK) Cancer Center. We'll be discussing a novel approach to address financial toxicity that uses the electronic medical record to streamline referrals to financial assistance and counseling for high-risk patients. Our full disclosures are available in the show notes, and disclosures of all guests on the podcast can be found on our transcripts at asco.org/podcasts. Dr. Thom, it's great to have you on the podcast today. Dr. Bridgette Thom: Thanks so much for having me. Dr. John Sweetenham: Dr. Thom, the high costs of cancer care have caused major financial distress for many patients and their families. And this, of course, has been the subject of a great deal of literature in recent years. As you noted in your poster presentation at the recent ASCO Annual Meeting, there are limited interventions, despite a need for patient level and system-based solutions (Abstract 6596). Listeners to our podcast will remember a previous discussion that we had with Dr. Derek Raghavan from the Levine Cancer Institute, where they had instituted financial toxicity grand rounds to partially address this problem. Can you tell us about the novel approach that you and your colleagues explored using the electronic medical record to streamline referrals for financial assistance and counseling? Dr. Bridgette Thom: I first have to credit our team for this work. Dr. Emeline Aviki, who is a gynecological surgical oncologist with keen interest in affordability and payment models, founded the MSK affordability working group several years ago. The first priority of the group was to determine the scope of financial hardship at our institution. At the time, we were absent a systematic screening process. So she, our data analysts, and representatives from our Patient Financial Services Program, developed proxy measures to figure out which patients might be having financial issues. Looking through the medical record, we found those patients who had used one of our Patient Financial Services assistance programs, those who had billing issues, and those who had been referred specifically to social work for a financial issue. And in doing so, we found out that about 25% of our patients over a 2-year period were facing some sort of financial issue. Looking closer at that data, patients experiencing financial hardship weren't necessarily being connected to the resources that we had available, which include copay assistance programs, financial assistance programs, and support for non-medical essential needs. So, for example, we had about 1 in 6 patients who had some sort of payment issue, but only about 20% of them had applied for financial assistance. And we wanted to figure out why this was happening and review the process. In doing so, we discovered that too much burden was being placed on already burdened social workers who had to triage all those issues. So Dr. Aviki in her wisdom realized that care providers, physicians, advanced practice providers (APP), nurses needed to make direct referrals to the resources that we had. So we had a place for patients to go, we just needed an easier mechanism for them to get there. And that was the birth of the financial toxicity order set. And she and her team really powered through the developmental and testing phases working with IT, our strategy administration groups, clinical end users, our PFS team, that's Patient Financial Services. We built this order set that allows clinicians directly to refer to our resources. So clinicians, either through their discussions with patients or if patients bring up an issue, through the order set they can select a reason for a referral, the urgency of referral, the clinical location, etc. And then those orders go directly to our Patient Financial Services staff who then contact patients. We piloted this program in late 2020, early 2021 on 1 service, and then used that feedback to roll out the program first to our outpatient clinics and then to inpatient. That process involved a lot of educational efforts, getting the word out, and working with IT and our strategy team to stay on top of the data and monitor referrals over time. Dr. John Sweetenham: Thanks. Could you say just a little bit more about the educational process that you use? I noticed in looking at your poster that the bulk of referrals came either from the clinic nurse or from the APP. Did you tailor your education in any way to the specific provider that was involved? How did you do that piece? Dr. Bridgette Thom: Our affordability working group is an interdisciplinary team and we have nurses, social workers, physicians. So we did a lot of grand rounds work tailored to the audience be it by disease type or clinical role. Dr. John Sweetenham: Great, thank you. This is clearly great work. There's a lot of useful and helpful information in your abstract and in your poster. What would you say are the key takeaways from the intervention? What would you say about the scalability of this approach into community practice as opposed to a very large institution such as yours? Dr. Bridgette Thom: One key takeaway from a process perspective was the need, like I said, for an interdisciplinary approach to handling the issues. That might seem obvious, but it was really crucial to the success of the project to engage key departmental stakeholders and decision makers very early in the process and keep them informed throughout the development of the order set. That definitely helped us to smooth a potentially bumpy road when we're dealing with big systems change. From an outcomes perspective, a key takeaway is the importance of having actionable items to empower the care providers. So while our institution has this amazing program, our Patient Financial Services program which provides counseling, and connects patients to tangible resources, this type of intervention I think could be scalable or applicable to a community practice or smaller hospital, provided there's somebody, a social worker, patient navigator, [or] nurse, that can be a connection for patients and those potential resources that do exist out there. For us going forward, we're going to continue to evaluate the order set, both from the clinical end user and then also the Patient Financial Services staff to learn more about their perspectives and what can be adapted in the order. We also, of course, want to learn from our patients about their experience with the process, and so we have projects, both research and program evaluation, in the works to consider their perspective. Dr. John Sweetenham: Great, thank you. And I guess 1 of the other aspects of this where there is obviously substantial opportunity is that, of course, currently, you're still reliant upon the provider to place the order. And I wonder whether you feel that some form of screening for social need and financial hardship could be embedded within the electronic health record as a key next step, so that you proactively identify those high-risk patients. Dr. Bridgette Thom: Definitely. And that is, in fact, our next step. We are currently piloting our financial hardship screening tool on 4 large services at our institution. The objective here is to, like you said, proactively identify patients who might be at risk and connect them to resources, be it tangible resources, or just counseling or insurance guidance, [and] do that before the hardship can occur. And the goals of our pilot phase are to (1) develop and refine a tool that's both predictive, but also feasible to administer within a busy clinic setting. And then also (2) to work with our interdisciplinary team to adapt the workflow. We can have a great tool, but if we don't have a way to administer it in a clinic, it's not going to do us any good. So for us, that means listening to feedback from, first and foremost, our patients and then the key stakeholders in the process. Our nurses have been integral to this process. We also, of course, our Patient Financial Services, staff, the clinical operations staff, obviously, IT, social work. And once we have these processes figured out and we have our tool solid, we will hopefully expand the screening to all services, and then use data to figure out the optimal screening interviews by disease and treatment type because we feel that this could vary by a patient's treatment trajectory. Dr. John Sweetenham: You note in your poster that additional multilevel interventions are needed to address the problem of financial toxicity at a systems level, and of course, what you have done here is a really great and important step in helping to identify those patients. But identifying those patients who are at particular risk is only beginning of addressing the issue. Could you elaborate a little bit more on other areas that you're exploring in terms of the interventions that you're using? Dr. Bridgette Thom: Sure. And this idea of multi-level interventions comes from my social work training, where there's an emphasis on viewing the individual as being part of a series of dynamic and interconnected relationships and systems: the social ecological theory. So if we think of concentric circles with the patient at the center, there are cascading relationships that are going to impact the course of their care. We radiate out to families and caregivers, a patient's workplace if they're employed, the hospital and the providers there, and then look to bigger systems where a patient lives, their town. If it's in an urban setting or a rural setting, the type of insurance that they have, if it comes from their employer, or if it's a different insurance system, their community and then of course, broader, social, societal, more macro issues. My point and that of many others who work in this space is that we have to consider the context. We can't just build and test interventions that focus on a patient because the patient isn't existing in a bubble. They're existing in relationships with their caregivers, their health care providers, their health care system. And all of that exists in, for lack of a better word, a broken system of structural inequality, systemic racism, and conflicting values about health care as a right. Patient-level interventions are indeed important, but we can't place the burden solely on the patient. And we, as researchers and clinicians in this space, really need solutions that are going to reach across systems. I think, like you said, this project demonstrates that and this is something that I hear from patients in other work that I'm doing. For example, I'm working on a digital intervention to help young adult cancer survivors to build their financial capability and build their understanding of the health care system and insurance systems and financing and all of that. As I co-develop this intervention with patients and survivors, I'm hearing, 'This is great. I'm glad I'm learning these things, but at the same time, my co-pays are unmanageable,' Or, 'I might have to skip my survivorship appointment because I can't afford to take off work that day.' I think we have to really think about, like I said, the context and the bigger picture of the scope of the problem and build and develop interventions that acknowledge that. Dr. John Sweetenham: Well, as you say, very complex, multi-level problem and many interventions needed. But congratulations and kudos to you and your colleagues for addressing one component of this. And we're really looking forward to seeing how this develops and progresses in the coming years. And I'd like to thank you, again, for sharing your insights with us today on the ASCO Daily News podcast and telling us a little bit more about this great work. Dr. Bridgette Thom: Thank you so much for having me. I want to just acknowledge all of the work of our team. It has really been a team effort. We're looking forward to our next steps. Dr. John Sweetenham: And thank you to our listeners for joining us today. You'll find links to the poster discussed today on the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. You can hear more about the MSK Affordability Working Group's efforts on the podcast, Cancer Straight Talk from MSK.   Disclosures: Dr. John Sweetenham: Consulting or Advisory Role: EMA Wellness Dr. Bridgette Thom: Stock and Other Ownership Interests (Immediate Family Member): Caladrius Biosciences, Mediwound, Sierra Oncology, Lipocine, MEI Pharma, Oncternal Therapeutics, Avadel Pharmaceuticals, Chimerix, Avidity Biosciences, Sutro Biopharma, Adma Pharma, Concert Pharmaceuticals, Processa Pharmaceuticals, Curis           An, IMV, Arcus Biosciences, Iovance Biotherapeutics, Qiagen, Revance Therapeutics, DermTech, Zimmer BioMet, Axonics Modulation, Halozyme, Autolus, Pavmed Inc       , Mereo BioPharma, and AADi Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.    

Dr. Rachna Shroff, of the University of Arizona Cancer Center, tells guest host, Dr. Shaalan Beg, of UT Southwestern's Harold C. Simmons Comprehensive Cancer Center and Science 37, about advances in precision medicine for pancreatic cancer featured at the 2022 ASCO Annual Meeting. She also highlights compelling new data from the FOLFOX, FOENIX-CCA2, and HERB trials in hepatocellular carcinoma, cholangiocarcinoma, and biliary tract cancer.   TRANSCRIPT Dr. Shaalan Beg: Hello and welcome to the ASCO Daily News podcast. I'm Dr. Shaalan Beg, your guest host of the ASCO Daily News podcast today. I'm an adjunct associate professor at UT Southwestern Simmons Comprehensive Cancer Center and vice president of oncology at Science 37. I'm delighted to welcome Dr. Rachna Shroff, the associate dean for clinical and translational research and the chief of gastrointestinal (GI) medical oncology at the University of Arizona Cancer Center where she's also the interim chief of Hematology-Oncology. Dr. Shroff is also the chair-elect for the Gastrointestinal Cancer Symposium. Today we'll be discussing key abstracts in GI cancer that were featured at the 2022 ASCO Annual Meeting. Our full disclosures are available in the show notes and disclosures of all our guests on the podcast can be found on our transcripts at asco.org/podcasts. Dr. Shroff, thank you for being on the podcast today. Dr. Rachna Shroff: Thank you so much for having me. Dr. Shaalan Beg: Let's begin by reviewing what is new in the realm of precision medicine in GI cancers. One of the diseases where precision medicine has not made adequate inroads is pancreatic cancer. One of the most common mutations in pancreas cancer is KRAS, but there haven't been a lot of treatments that can target the most common forms of KRAS. What did we hear at ASCO22 regarding precision medicine and pancreatic cancer? Dr. Rachna Shroff: I agree, I think that the area of precision oncology is, unfortunately, lagging behind a little bit in pancreatic cancer. But I think as we have gotten better and better with our comprehensive genomic profiling, we are identifying subsets of patients within pancreas cancer who are potentially amenable to targeted therapies. You already mentioned KRAS mutations, and we obviously have a number of inhibitors in development in that space, though, we are still missing that key G12D mutation that we see in pancreas cancer. But what I think was really interesting that came out of ASCO22, was a lot of interest and emphasis on better understanding the KRAS wild-type patients in pancreatic cancer. Now, this is obviously a smaller subset of patients, given that the majority of patients have KRAS mutations. But there was a really interesting abstract, LBA4011, that looked at patients with locally advanced or metastatic pancreatic cancer, who were KRAS wild-type. They actually received gemcitabine in combination with a monoclonal antibody targeting EGFR and nimotuzumab. This was a study that was done entirely in Asia. It involved 92 Chinese patients that were randomly assigned to receive the combination of nimotuzumab with gemcitabine. What was interesting in this study is that the patients were found in the full analysis set to have a significantly longer median overall survival of 10.9 months versus 8.5 months with a hazard ratio of 0.5. So, that of course was intriguing and provocative for sure. Similarly, the other endpoints were also somewhat intriguing in terms of improvements in the median progression-free survival (PFS), etc. And specifically, patients without biliary obstruction had a longer PFS, which was an interesting finding as well. The nimotuzumab overall was pretty well tolerated and not any sort of surprising treatment-related adverse events (TRAEs) were noted. And so, this is definitely a drug that, I think, piques our interest in terms of being able to target patients with KRAS wild-type pancreatic cancer. I think that questions, however, that remain, and I think require further study is really understanding what this drug could do in combination with the chemotherapy combinations that we use more frequently in metastatic pancreatic cancers such as gemcitabine and paclitaxel or 5FU-based regimens like FOLFIRINOX. I think given that it is a relatively well-tolerated drug, it would be a very reasonable thing to investigate this drug further in the KRAS wild-type population with the kind of modern-day chemotherapy regimens that we use. And I think, of course, we all know that it is useful to be able to look at these types of drugs in a more global population. And so, a larger patient set I think would be very useful as well, but at least it tells us that there is a way to think about our KRAS wild-type patients with pancreas cancer and that perhaps we really need to understand and identify those patients' potential for precision oncology. Dr. Shaalan Beg: One of the GI cancers that has been a hotbed for precision medicine is cholangiocarcinoma, a disease that's very close to your heart. What updates did we hear at ASCO22 regarding cholangiocarcinoma and precision medicine? Dr. Rachna Shroff: This space of targeted therapy and cholangiocarcinoma has been incredibly exciting for the last few years and I think drug development has been rapid-fire in that space. The oldest, if you will, target that we've been thinking about for some time is the FGFR2 fusion patient population. And in Abstract 4009 by Dr. Goyal and colleagues, we saw the results of the FOENIX-CCA 2 trial which was looking at an oral FGFR inhibitor (futibatinib) in patients with intrahepatic cholangiocarcinoma, who harbor FGFR2 fusions and gene rearrangements. We had initially seen some of this data presented a few years back, but this was the updated data set. It was a single-arm phase 2 study that involved patients with advanced intrahepatic cholangiocarcinoma who had identified FGFR2 gene fusions, and they received futibatinib daily until progression. This was a traditional single-arm phase 2 study with a primary endpoint of overall response rate. At the final data cut, with a median follow-up of 25 months, there's actually a confirmed overall response rate of 41.7%. And I think that what was really exciting about this is this is a refractory patient population. So, in patients who have refractory cholangiocarcinoma, the other drugs, the non-targeted therapy drugs that we think through, really have response rates more in the single-digit to 10% range and so to have a confirmed overall response (OR) over 40% is truly exciting. The duration of the response was also exciting. This is not just a drug that works briefly, it has a duration of response of 9.5 months. And the mature median overall survival was 20 months. And in a disease which we talk about with the ABC-02 data of GemCis, a median OS in advanced disease of 11.7 months. This is really, really exciting for patients who harbor this fusion or gene rearrangement. We know that that's seen in about 10 to 15% of patients. So, again, we're dealing with a smaller subset, but it clearly demonstrates the need to identify FGFR2 gene fusions, so that we can offer these types of targeted therapies. This was not the first FGFR inhibitor that we have seen data on and in fact, we have 2 drugs already U.S. Food and Drug Administration (FDA) approved. And so, when we look at the common treatment-related adverse events that were identified with the futibatinib, there are really class effects related to FGFR inhibition like hyperphosphatemia, alopecia, dry mouth, nothing that really stood out or that was concerning. And so, I think this final analysis for the FOENIX study really just reaffirms the utility of futibatinib in patients with FGFR2 gene fusions, and the mature OS data, the duration of response, all of this really aligns with the need to identify patients with this alteration so that we can, post-gemcitabine based therapies, offer this targeted therapy or an FGFR inhibitor in general to these patients. I think the other really exciting abstract in the glandular carcinoma or biliary tract cancer space was Abstract 4006. This was the updated data from the HERB trial, which was an investigator-initiated multicenter phase 2 trial looking at trastuzumab deruxtecan (T-DXd) in patients who have HER2 expressing unresectable or recurrent biliary tract cancer. Trastuzumab deruxtecan, I'm sure everybody has been hearing about because it has been incredibly effective in HER2 alterations across a myriad of different disease sites. And so, not wanting to be left out, biliary tract cancers were investigated in this study with patients who had HER2 expression, so, that was HER2-positive IHC3+ or IHC2+/ISH+, and they also looked at HER2-low expressing patients, and [whose disease] were refractory or intolerant to gemcitabine-based therapy with the primary endpoint of overall response rate. So, in the HERB trial, a total of 32 patients were enrolled. 24 of them were HER2-positive and 8 were HER2-low and they all received trastuzumab deruxtecan. When you look at the efficacy data, the confirmed overall response rate in the patients with HER2-positive was 36.4%, which again, as I said, in a refractory patient population is certainly very exciting data. And the overall disease control median, PFS, and median OS were all pretty encouraging in terms of efficacy. What was also kind of intriguing was that there was some efficacy seen even in the patients who are HER2-low. Now, this is, in my opinion, a slightly less exciting amount of efficacy, but still important to note that the overall response rate in HER2-low was 12.5% with a median PFS that was also somewhat exciting at 4.2 months. And so, there is a potential clearly for targeting patients with HER2-high or HER2-positive with trastuzumab deruxtecan, and I think in the patients who are HER2-low, we need to better understand the potential utility. The common treatment-related adverse events that we see were the typical things that we've heard about with trastuzumab deruxtecan, but I think the one thing that was really worth noting was 8 patients or 25% of patients had interstitial lung disease (ILD), which we know is an important identified safety concern for patients who receive trastuzumab deruxtecan, and I think that's a pretty sizable number of 25%, so, I think that's going to really require a little bit more fleshing out for us to understand the safety for these patients. One question that a lot of us have had is whether these are patients who have received gemcitabine, which we know can also cause pneumonitis. And so, I don't know if we're seeing a higher percentage of ILD because of, 'priming' with prior gemcitabine. But regardless, I think this is just proof of principle that again, we need to identify patients with biliary tract cancers that have HER2-positivity because we now have a number of drugs including potentially trastuzamab deruxtecan to target [their disease] with after gemcitabine-based treatments Dr. Shaalan Beg: Absolutely. Any new biomarkers to keep on the radar for our listeners? Dr. Rachna Shroff: I think there are a lot of really exciting targets. One that was talked about and that we saw data on at ASCO [Annual Meeting] was from Abstract 4048, which looked at claudin [18]. Claudin is basically a transmembrane protein that kind of helps maintain the tight junctions between cells. In gastric cancer, in particular, we look at claudin 18 isoform 2, and there are 18.1 and 18.2 gene expressions that have been identified in gastric cancer. So, there was a very comprehensive abstract that was presented of over 1,900 samples that underwent comprehensive profiling by next-generation sequencing. And the patients were identified with claudin 18.1, and 18.2, high versus low. Claudin 18.2 expression was actually detected in 97% of the samples. It's slightly lower with claudin 18.1 at 63%. It's important to note that the primary tumors had higher expression levels than the metastatic tumors, so those were really the tumors in which they did a deeper dive. And in the process of doing this deeper dive, they did a really interesting kind of better understanding of the immune microenvironment and the immune profile in the samples that had claudin expression. And what was identified is that there was an inverse relationship basically between claudin 18.1 and 18.2 expression and correlation with PD-L1 positivity, tumor mutational burden (TMB)-high, M1 macrophages expression, NK cell presence, CD4 positive T-cells, myeloid dendritic cells. And so, there's clearly something between the presence of this claudin expression and the effect it has on the immune microenvironment. I think that's very relevant to keep in mind because as we all know, there's a whole space of drug development focused right now on anti-claudin 18.2 monoclonal antibodies, as well as a target for antibody-drug conjugates (ADC) and cellular therapies with CAR T-cell therapies being developed specifically against claudin 18. And so, understanding the immune microenvironment and the interaction between the claudin expression will be really important as we continue to charge forward in that space. Dr. Shaalan Beg: Absolutely. Very, very exciting. Sticking with the liver pancreas theme, what other studies piqued your interest with regards to hepatocellular carcinoma (HCC)? Dr. Rachna Shroff: It's a really exciting time in HCC. I mean, we actually have drugs that are working in the advanced space. And so, now there's a lot of interest in shifting to looking at preoperative neoadjuvant, and adjuvant approaches and what we can do to improve disease-free survival and overall survival in patients who are able to undergo prior resection. So, Abstract 4013 looked specifically at the efficacy and safety of adjuvant hepatic arterial infusion chemotherapy with FOLFOX. And this was a randomized open-label phase 3 trial. It actually included a total of 315 patients between 5 different centers and patients were randomly assigned to receive either 1 to 2 cycles of adjuvant HAIC FOLFOX (Hepatic Arterial Infusion Chemotherapy FOLFOX) versus just follow up, the control group had no adjuvant treatment, and the primary endpoint was disease-free survival here and in the intention to treat population, there was a significantly improved median disease-free survival at 27 months versus 11 months in the patients who were on the control arm. And there was a protocol analysis, there were a number of other efficacy endpoints including disease-free survival rates at 1, 2, and 3 years. And everything kind of leaned towards and or suggested an improvement with the utility of HAI FOLFOX in patients who undergo complete resection. It should be noted that this included patients specifically who had microvascular invasion on their resection. And so, these are patients who are at higher risk for recurrence as we know. This to me suggests that there could be a role for adjuvant treatment in patients who undergo complete resection with microvascular invasion (MVI). HAI is a very specific technique and it requires a highly skilled center in the placement of HAI pumps. And we're seeing more and more trials across the U.S. as well investigating the role of HAI in advanced disease and in perioperative approaches. And so, I think this is an area of much-needed continued research. There are, of course, a number of ongoing adjuvant studies looking at immunotherapy in the adjuvant setting. And so, it'll be really important to see how those read out and then to try to put all of these in context so that we can better understand local therapy like HAI FOLFOX versus more systemic adjuvant approaches like immunotherapy. Dr. Shaalan Beg: Thank you very much, Dr. Shroff for sharing your valuable insights with us. I really appreciate you taking the time to spend with us and our listeners. Dr. Rachna Shroff: Thanks so much. I enjoyed it. Dr. Shaalan Beg: And thank you to our listeners for your time today. You will find links to the abstracts discussed today in the transcript of this episode. Finally, we'd really like to hear your feedback. If you could please take a moment to rate, review, and subscribe wherever you get your podcasts. Thank you very much!   Disclosures: Dr. Shaalan Beg: Employment: Science 37 Consulting or Advisory Role: Ipsen, Array BioPharma, AstraZeneca/MedImmune, Cancer Commons, Legend Biotech, Foundation Medicine Research Funding (Inst.): Bristol-Myers Squibb, AstraZeneca/MedImmune, Merck Serono, Five Prime Therapeutics, MedImmune, Genentech, Immunesensor, Tolero Pharmaceuticals Dr. Rachna Shroff: Consulting or Advisory Role: Exelixis, Merck, QED Therapeutics, Incyte, Astra Zeneca, Taiho Pharmaceutical, Boehringer Ingelheim, SERVIER, Genentech, Basilea Research Funding: Pieris Pharmaceuticals, Taiho Pharmaceutical, Merck, Exelixis, QED Therapeutics, Rafael Pharmaceuticals, Bristol-Myers Squibb, Bayer, Immunovaccine, Seagen, Novocure, Nucana, Loxo/Lilly, Faeth Therapeutics Disclaimer: The purpose of this podcast is to educate and inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.  

Dr. Allison Zibelli, of the Sidney Kimmel Cancer Center – Jefferson Health, and Dr. Hope Rugo, of the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, discuss the practice-changing DESTINY-Breast04 trial as well as novel therapies in metastatic HR+/HER2- breast cancer from the TROPiCS-02 and MAINTAIN studies, all of which were featured at the 2022 ASCO Annual Meeting.   TRANSCRIPT Dr. Allison Zibelli: Hello. I'm Dr. Allison Zibelli, your host for the ASCO Daily News Podcast today. I'm a vice-chair and breast medical oncologist at the Sidney Kimmel Cancer Center, Jefferson Health in Philadelphia. My guest today is Dr. Hope Rugo, a professor of medicine and the director of Breast Oncology and Clinical Trials Education at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco. We'll be discussing key advances in breast cancer that were featured at the 2022 ASCO Annual Meeting. Our full disclosures are available in the show notes, and disclosures of all guests on the podcasts can be found on our transcripts at asco.org/podcasts. Hope, it's great to talk to you today. Dr. Hope Rugo: Nice to talk to you, too. Dr. Allison Zibelli: Let's begin with perhaps the most exciting abstract at ASCO this year, which was the DESTINY-Breast04 study, that's LBA3, a randomized phase 3 study of trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-low, unresectable and/or metastatic breast cancer. What are your thoughts about this study? Dr. Hope Rugo: Well, of course, this is a hugely practice-changing study as was noted in the second-to-last slide by the discussant [Dr.] Pat LoRusso. So, antibody-drug conjugates are really the next step in delivering chemotherapy to cancer cells. The antibody-drug conjugates allow targeted delivery of a toxin to the cancer cell. I think we didn't understand how important this was going to be. These second, sort of, verging on third-generation antibody-drug conjugates use an antibody approach and to then have a new generation of linkers, which allow the drug to be released locally, but to then have drugs which pack a big bang for the buck. So, the way antibody-drug conjugates are constructed, you need to have a drug that actually can't be given as a naked drug because it's too toxic because you're giving just very small amounts of this drug that are delivered directly to the cancer cell. And the other really critical part of this is that the drug-to-antibody ratio of at least the successful and new antibody-drug conjugates (ADC) is quite high in the 7.5 to 8 toxins per antibody. Now, what that's resulted in is really interesting, is that there's a bystander effect. So, the toxin itself can leak out of the cancer cell that it's targeted and kill neighboring cells, but also because of the construct of these antibody-drug conjugates, what's likely happening is even if the cancer cell's a very low expression of the target, really low, you're able to actually get that ADC into the cancer cell to kill the cancer cell. So that may be a big part of the so-called bystander effect. So trastuzumab deruxtecan is biosimilar trastuzumab linked to a topoisomerase inhibitor deruxtecan, and what happened here was that of course, we saw remarkable data in HER2+ disease, unbelievable p-values in DESTINY-Breast03 compared to T-DM1, a first-generation ADC. But in DESTINY-Breast04, we targeted a population of patients largely with hormone receptor-positive disease who had a little expression of HER2, 1 plus or 2 plus by immunohistochemistry and no gene amplification. And this trial, which randomly assigned patients 2:1 and included just 58 patients with triple-negative disease. So in this trial, 480 had hormone receptor-positive breast cancer, a median of 1 line of prior chemotherapy. They were only allowed up to 2. They were refractory to endocrine therapy, a median of 3 lines of endocrine therapy. In the overall patients and in the hormone receptor-positive patients, there was actually a doubling in progression-free survival (PFS). It started very early, and it continued throughout, and at every landmark analysis, T-DXd was better than the treatment of physician choice that patients were randomly assigned to. It's also important when you're thinking about trials like this to think about what the treatment of physician choice was, and it was all chemotherapy regimens we would use. Paclitaxel, nab-paclitaxel, capecitabine, eribulin, or gemcitabine. And, so, I think that that doesn't bring up any questions. When they looked at the hormone receptor-positive group, they saw, if anything, even a bigger benefit overall. Now, the other endpoint of this trial was overall survival, and at this first analysis, they saw an improvement in overall survival that was quite dramatic. The absolute difference was 6.4 months, which is pretty amazing for an overall survival difference. And then they looked at this exploratory endpoint at the 58 patients who were valuable at triple-negative breast cancer, and then that group of patients, also saw an improvement in PFS of 5.6 months, an improvement in overall survival of 9.9 months, very small group, but amazing data. The forest plots are exactly what you want to see, all the dots line up to the left of 1, and overall responses improved. One of the concerns with this drug has been toxicity. The toxicity showed no new toxicity signals, which is really important. Nausea is the biggest issue that we deal with. It's mostly grade 1 and 2, but still something that's important to manage. A little bit of hair loss, not much in the way of bone marrow suppression, which is interesting. Interstitial lung disease (ILD) or pneumonitis continues to be an important issue to follow. 12% of patients had ILD of any grade. Most of it was grade 1 and 2, but 3 patients died, representing 0.8%. So, this really highlights the importance of monitoring and managing pneumonitis. Regardless of that, few patients had a reduced ejection fraction, but again, very, in general, low grade. This is really a new standard of care, and the standing ovation was really due to the fact that all we do is dedicate ourselves to trying to help patients live longer and better with their cancers, and in this trial, we have a huge win that has no qualifications. We can help patients not only control their disease longer but live longer with T-Dxd compared to standard chemotherapy. Dr. Allison Zibelli: So, Hope, I know as a practicing medical oncologist, I find that our metastatic triple-negative patients are often the biggest therapeutic challenges for us. Will they be doing larger studies with these patients that are HER2-low? Dr. Hope Rugo: It's a really good point. About 65% of patients with hormone receptor-positive disease or so-called HER2-low, centrally confirmed in the study. So, a fair number of people, about a quarter, did not have HER2-low disease when they were tested centrally. In the triple-negative population, who really are ER, PR, HER2- by standard definitions, about a third of the patients might have HER2-low disease. So, there's a lot of interest in further exploring that and looking at the patients who have ultra-HER2-low disease, so between and 1 plus a little bit of expression. That's been studied in the hormone receptor-positive population in DESTINY-Breast06. But there's a lot of interesting further defining that triple-negative population, so to speak, they're going to be triple-negative plus now and understanding what the benefit is in that population. So definitely will be looked at more now moving forward. Dr. Allison Zibelli: Thank you. So, let's move on to Abstract 1002. And the results from the phase 1, 2 study of patritumab deruxtecan, a HER3-directed antibody-drug conjugate, and patients with HER3 expressing metastatic breast cancer. What are your thoughts about this study? Dr. Hope Rugo: That's a really interesting, another one of these second- to third-generation antibody-drug conjugates. It's just the antibody, instead of being the usual, sort of, HER2 or TROP2 that we're used to thinking about is directed to HER3, 1 of the HER family of proteins. This is interesting. There's actually been a lot of work trying to target HER3 with naked antibodies with disappointing results, although I have to say most of the studies really didn't push it too far. So, with this antibody drug construct, deruxtecan, which is the same as in T-DXd and another TROP2 ADC Dato-DXd is used. So, I will say they do need to change the toxin in the next generation of ADCs. But they looked at, at first did a dose-finding study which has previously been presented, and then a dose expansion in both hormone receptor-positive HER2-negative disease and triple-negative disease. All the triple-negative patients had HER3 high disease by immunohistochemistry, and the hormone-receptor-positive patients were enrolled in 2 cohorts, HER3 high and HER3 low. And the median number of prior treatment regimens that patients had received in the hormone-receptor-positive group was 6 and 2 for the triple-negative group, but there was a huge range, up to 13 lines of treatment. They only had 14 patients with HER2+ disease. So, it's a little bit hard to know what to do with that patient group, but they were heavily pretreated 5.5 prior lines of therapy. The confirmed overall response rate in the 113 patients with combined HER3 high and low was 30%, very impressive, heavily pretreated patients. For triple-negative disease all HER3 high, it was 23%. Again, very nice. And there were 14 patients with HER2+ disease that also were HER3 high. It was about 43%. So those are nice responses, but we always want to know how durable is that. The duration of response ranged from 6 to over 8 months in those 3 different groups. So, these were quite durable. It wasn't any 2- to 3-month duration of response. So very impressive. And then when they looked to see, did it matter whether you had HER3 expression that was high or low in the hormone-receptor positive group, they actually did see responses in the HER3-low group, some very good responses. Overall, there were less patients in that group, but it does suggest that maybe you would still see responses in the HER3-low group, very impressive. And then 1 really interesting correlative study they did was they looked to see what happened to the HER3 expression on the tumor cell over time, and it went down. So, you treated the HER3 expression in most of the patients just dropped off completely, which is really interesting. It didn't have any association with clinical activity, but it's sort of an interesting correlative endpoint. This is a drug that overall was pretty well tolerated. They saw a similar toxicity to T-DXd with a lot of nauseous, a little bit of alopecia, a little bit more bone marrow suppression than we're used to seeing with T-DXd. So, neutropenia was seen in about 10% of patients at the lower dose and about a quarter of the patients at the higher dose. Overall, pretty well tolerated. Now, interstitial lung disease is a toxicity with this construct, and they saw ILD of 7% but most cases were grade 1 and 2. The other interesting toxicity that's unique to this agent is thrombocytopenia. So, they saw a grade 3 or greater rate of thrombocytopenia of 27% in the lower dose group, and in the larger group that received the higher dose, 39% of grade 3 or greater thrombocytopenia, so platelets less than 100,000. Turns out that when you stop the drug, the platelets do come back, so that's a good thing. Sometimes we saw long-term thrombocytopenia with T-DM1. They didn't see bad toxicity like bleeding, but it is something that needs to be managed with this drug because we're not great at managing thrombocytopenia. In any case, it has fast-track designation for another solid tumor, not breast cancer, and we'll have to see where this fits into our dizzying array of very effective ADCs now. Dr. Allison Zibelli: The practicing medical oncologist is not used to testing for HER3 in our patients with breast cancer. How common is it? Dr. Hope Rugo: HER3 expression is quite common in hormone receptor-positive disease, a little less common in triple-negative breast cancer. So, I think that we would see expression if we were going to be treating patients with this particular approach. Dr. Allison Zibelli: All right. Let's move on to Abstract 507, which reported long-term outcomes of adjuvant denosumab in breast cancer, specifically fracture reduction and survival results from 3,425 patients in a randomized double-blind, placebo-controlled ABCSG-18 trial. What are your thoughts about this study? Dr. Hope Rugo: Well, this trial, this is an update of a study that previously has been presented and published, most recent publication was in Lancet Oncology in 2019, and these patients were randomly assigned to receive denosumab at 60 milligrams, important to note the dose, subcutaneously every 6 months versus placebo every 6 months, and they did get placebo subcutaneous injections. And this treatment continued through their endocrine therapy. They showed a dramatic reduction in fracture rate, and that has been maintained over time. We were really surprised enough to suggest that maybe Austrian people didn't go into the sun, so they got more Vitamin D deficiency, hard to know, but the hazard ratio is 0.5. It's unbelievable the number of fractures, 92 for denosumab but 176 for placebo, a P value of less than .0001. So, this is a real endpoint, treating patients who are receiving endocrine therapy that, in this case, non-steroidal aromatase inhibitor therapy that can increase bone loss, have a reduced fracture rate when they received denosumab. So that is the big take-home message, and a medium follow-up of 8 years. But the secondary endpoints included disease-free survival. They had about 20% disease-free survival events and 8% deaths, and what they saw was really interesting. So, the caveat is that 16% of patients were unblinded at the first analysis and half of them got denosumab, so it messed up their results a little bit, but the disease-free survival was significantly better in patients who received denosumab, and the hazard ratio of 0.83 and the hazard ratio does not cross 1. So that's very interesting, and even overall survival, they looked at 2 other endpoints, bone metastasis-free survival, and overall survival. They also trend towards an improvement with a hazard ratio of 0.8 for both of them. And they didn't actually see toxicity. So, patients' brittle bone fractures and osteonecrosis of the jaw (ONJ) are all concerning, but they really just did not see any risks in this patient population. I think there was 1 patient that had what they thought was a brittle bone fracture. Obviously, they watched the mouth very carefully as well. Really dramatic, and I think it's kind of disappointing that we never had any registration approach in this, and also not well-understood why the D-CARE study did not show a benefit, but I think D-CARE was designed differently. This is a better design to focus on our patients and the specific issues, and I think it's intriguing and should be considered as part of our treatment regimen for patients who are at risk for bone loss and have early-stage breast cancer on an aromatase inhibitor. Dr. Allison Zibelli: I've been using DEXA scans and offering denosumab to my patients on AIs that have osteopenia or osteoporosis. Should we be considering it in women with normal bone mass? Dr. Hope Rugo: I think not yet. Unfortunately, this trial was not immediately powered for cancer outcome, although the data are very encouraging. We don't know what the relationship is to bone loss, and providing an environment that's friendlier for cancer cells. So, do you have to have bone loss in order to have the risk that you're reducing with these agents? Certainly, that's what we've seen with zoledronate. So, I think that we don't have sufficient data to use this simply to treat cancer, but I do think that we should be considering this as an agent to give patients who have bone loss, either when you're starting an aromatase inhibitor or during the course of therapy. I think it's well tolerated, and a subcutaneous injection is not difficult. One of the questions that's come up for people is do you get bone loss that increases your risk of fracture after you stop therapy. But clearly from these updated data, these patients were off therapy. They did not have an increase of fractures and the patients treated with denosumab fared much better, I mean the hazard ratio of 0.5. Dr. Allison Zibelli: Let's move on to TROPiCS-02. That's LBA1001. This is a randomized phase 3 study of sacituzumab govitecan versus treatment of physician's choice in patients with hormone receptor-positive, HER2-negative advanced breast cancer. How do you think this study will impact practice? Dr. Hope Rugo: That's a great question. I presented this data, and I think I presented it on a Saturday, and on Sunday we saw the plenary talk of DESTINY-Breast04. These patients enrolled in TROPiCs-02 had a median number of lines of prior chemo 3 with a range of up to 8 actually, compared to a median number of lines as 1 in the DESTINY-Breast04 population. We included all hormone receptor-positive HER2 negative-advanced breast cancer, not centrally confirmed. They included just the HER2 low subset that was centrally confirmed. Everybody in our study had received prior CDK4/6 inhibitors compared to about 70% in DB04. And then 95% of patients in this trial had visceral mets. So, we did really treat a patient population who had very advanced high risk hormone receptor-positive breast cancer. As you know, we saw an improvement and progression-free survival with a hazard ratio of 0.66 meeting the endpoint. We needed a hazard ratio of 0.7, highly statistically significant P value .0003, but the median difference in PFS was only 1.5 months, and overall survival data is not yet mature. So that's brought up the question about how this drug should be used because there was a big fall off in the first 2 months where patients had rapid disease progression with heavily pretreated chemotherapy-resistant disease. We did landmark analyses and there were big separations in PFS at 6, 9, and 12 months, and 12 months, it was 21% patients free of progression and death at 1 year versus 7% for the TPC arm. So, it was a tripling of patients who were free of progression at one year. I think that's clinically relevant. This drug is associated with more neutropenia. That's the primary issue to manage, and probably half of the patients need growth factors at some point. When we looked at other endpoints response to ratio response, etc., we're better with Sacituzumab. So where does this all fit into our treatment paradigm. I think there's the HER2-low patients who will now receive T-DXd up in the, I hope, second line and not in lieu of endocrine therapy, when they're ready for chemo. But there are patients who don't have HER2-low disease and then there are patients who are going to be in the later line setting. So, I do think it still has a place in the treatment department, receptor-positive metastatic breast cancer. The results show that it was better than chemotherapy, physician choice based on our national and international guidelines, and that's better for our patients to have that option. Overall survival data obviously is looked for with great interest and that will help us put this into the right paradigm. And then I also hope that real world data will help us understand how sequential treatment with these different ADCs will benefit our patients. Dr. Allison Zibelli: This is really exciting. Do you think that we're maybe coming toward the end of conventional chemotherapy, especially for women with HER2-positive disease? Dr. Hope Rugo: I wonder if we are. I think we were interested in T-DM1 for HER2-positive disease early on. We've seen some really nice pathologic complete response data as well as adjuvant data in the attempt trial in patients who had stage I disease. Now that we have these second-, third-generation ADCs, T-DXd, I think this could potentially completely replace our chemotherapy. We still have to deal with alopecia. And I will point out ADCs are still chemotherapy. They're just a much more efficient and effective way of delivering treatment, and we need to be very careful to manage the toxicity. Dr. Allison Zibelli: Next, we're going to talk about the main pain trial that's LBA1004, which is a randomized phase 2 trial of fulvestrant or exemestane with or without ribociclib after progression on anti-estrogen therapy plus cyclin-dependent kinase 4/6 inhibition in patients with unresectable or hormone receptor-positive HER2-negative metastatic breast cancer, in other words CDK4/6 after CDK4/6. What are your takeaways here? Dr. Hope Rugo: First, just amazing that an investigator-initiated trial could do this well and be placebo-controlled. So, kudos to the principal investigator (PI) [Dr.] Kevin Kalinsky. This trial is a small phase 2 trial. A reasonable number, 119 patients were randomly assigned and evaluable patients could have received up to 1 line of prior chemotherapy for metastatic disease. If you had received prior exemestane, you received fulvestrant, if you received prior fulvestrant, you received exemestane, and actually if you looked at the number of patients who had received fulvestrant, it was 99 versus only 20 with exemestane. So important to keep in mind. If you looked at the overall population where the primary endpoint was progression-free survival, the hazard ratio is 0.57, just median PFS of 2.8 months in patients receiving endocrine therapy and placebo and 5.3 months for patients receiving endocrine therapy and ribociclib. So was this ribociclib after ribociclib or ribociclib after something else. 86% of patients had received palbociclib as their prior CDK4/6 inhibitor, and only about 10% to 14% had received prior ribociclib. So, there's a predominance of palbociclib followed by ribociclib. The other thing that's important to keep in mind is how sick this patient population was. Very few had received prior chemotherapy in the less than 10% range, visceral metastases in about 60%. So that's helpful. Only 19% or so had received 2 or more endocrine therapies from metastases. So, most people did this as their second line treatment. The PFS, when you looked at fulvestrant or exemestane, looked like the benefit was relatively similar, but you know you got 20 patients in the exemestane arm. The hazard ratios, looking at the subgroup analyses, all looked pretty similar, and the overall response and clinical benefit rate were better with continuing the cyclin dependent kinases (CDK) inhibitor. There was interesting sub-analysis looking at mutations and how that affected things. And they looked at patients who had ESR1 mutations or had wild-type ESR1. 42% had ESR1 mutations at study entry, very similar to what we've seen. In that group of patients, remember it's only 33 where they had this analysis, they saw a lot of other mutations. So p53, PIK3CA, FGFR, CCND1—those patients did not benefit. Only 33 patients. No benefit at all, very short PFS, about 3 months. The patients who had ESR1 wild type seemed to benefit a lot, 45 patients going from about 3 months to a little over 8 months. So, this is all hypothesis-generating data. I wouldn't run out and use this as your standard of care now because it is small data. But when the patient doesn't have other good options, I certainly would consider switching the CDK and going on, add that to the next line endocrine therapy. It's important to switch the endocrine therapy. I think we really need to look at the ongoing phase 3 trials to give us better evidence basis and understand the impact of mutations and prior therapy on who might benefit from continued CDK inhibitors after progression on a CDK inhibitor. Dr. Allison Zibelli: I think this is a really exciting trial. We all have a lot of patients on palbociclib and letrozole who've been on for 4, 5 years, and would like to continue with this kind of treatment because the side effects are really manageable. So, I look forward to seeing what's coming in the future with the phase 3 trials. So, let's talk about Abstract 1015, which I thought is a great idea. It looks at the quality of life with ribociclib plus aromatase inhibitor versus abemaciclib plus AI as first-line treatment of hormone receptor-positive, HER2-negative advanced breast cancer, assessed via matching adjusted indirect comparison. Could you tell us what matching adjusted indirect comparison is and why you chose this for the study? Dr. Hope Rugo: It's an interesting question. How do you compare across trials? So, matching this kind of make analysis, we'll call it a make analysis for the purposes of this discussion, allows you to match patients and weight based on their characteristics that might affect patient reported outcomes. And that actually is a way of trying to do a fair cross-trial comparison. So basically, take the study population, you match the inclusion and exclusion criteria, and then you weigh the different criteria so that you can try and make a better association. It's the best way we know of comparing across trials. You know, a lot of people ask why we didn't have PALOMA-2 in here, and that's because they used a different patient reported outcome tool. So, you have to use the same patient reported outcome tool in order to compare. So that's why we did this analysis, and it sort of came on the heels of a survey that Fatima Cardoso presented at San Antonio in 2021, where patients identified diarrhea as a symptom they really didn't like more than everything else. And you can imagine, I think we all have that experience in practice, the unexpected nature of diarrhea and the fact that it does limit your activities and, therefore, quality of life are important. In this analysis, interestingly but not surprisingly, ribociclib favored abemaciclib in diarrhea, and there can be associated appetite loss, so ribociclib also favored abemaciclib for appetite loss. And I thought the last one was interesting—fatigue—because I wouldn't have assumed that fatigue would be different. And maybe it's associated with diarrhea. They have these funny arm symptoms that were better. We don't really know why that was, and it's hard to assess again. We're really not clear based on the differences between the drugs. So, there are limitations to the analysis, but I think that it helps us really in individual patients try and match patients' underlying symptoms with the best treatment to offer them the best quality of life as they're being treated in the metastatic setting. Dr. Allison Zibelli: I thought this study was great because it really centered the experience of the patient and the wishes of the patient. You don't see that designed into many clinical trials, the way this was. So, I thought that was a great feature of this study. Dr. Hope Rugo: I will say that all of the 3 studies that looked at CDK inhibitors, all those 3 studies included patient-reported outcomes. That's an important new approach that is really being focused on. Dr. Allison Zibelli: Do you consider the CDK4/6 inhibitors equivalent in efficacy, and could you substitute them to try to get the side effect profile that you want? Dr. Hope Rugo: Well, I think that we saw in the early stage setting that there are differences. Now, across the different trials, there are big differences in patient populations and inclusions as we saw in the PALOMA-2 results that were presented at ASCO [Annual Meeting], whether the patients had prior chemotherapy like in PALOMA-3, whether they had a short disease-free interval, the higher risk patients in PALOMA-2. The PALOMA trials were more broadly inclusive than the other 2 studies, the MONALEESA and MONARCH series of trials. So, we do have to be a little bit careful about comparing apples to oranges, but we have the early-stage results of MONARCH E showing a clinically important difference in outcome whereas the PALLAS and Penelope-B trials didn't. So that sort of puts us into a little bit of a question period. Are these all patient populations or are there differences between the agents? The PFS and the metastatic setting, all the hazard ratios line up. So, in truth, although I know the activity against cyclin-independent kinases are different between agents, we don't still really understand the clinical differences in efficacy, but I think we all are practicing using evidence-based medicine. I wouldn't, for example, substitute a different CDK4/6 inhibitor for abemaciclib in the treatment of early-stage breast cancer. We have to just learn how to manage the diarrhea and use prophylaxis and dose reduce early to manage this and make it tolerable for our patients. And in the metastatic setting, I think we need to follow evidence-based guidelines and use the best data available to decide on the right treatment approach and sequencing for our patients. Dr. Allison Zibelli: Thank you, Hope, for coming on the podcast today. This was a really interesting review of one of the most exciting ASCO [Annual Meetings] I've been to. And thanks for sharing your valuable insights with us and helping us make sense of all this really new exciting data. We really appreciate it. Dr. Hope Rugo: Thank you. And thank you so much for inviting me. Dr. Allison Zibelli: And thank you to our listeners for joining us today. You will find the links to all the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. That really helps other listeners find us. Thank you.   Disclosures: Dr. Allison Zibelli: None disclosed. Dr. Hope Rugo: Honoraria: Puma Biotechnology, Mylan, Samsung Bioepis, Chugai Pharma, Blueprint Medicines Consulting or Advisory Role: Napo Pharmaceuticals Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Genentech, Merck, Odonate Therapeutics, Daiichi Sankyo, Sermonix Pharmaceuticals, AstraZeneca, Gilead Sciences, Ayala Pharmaceuticals, Astellas Pharma, Seattle Genetics, Macrogenics, Boehringer Ingelheim, Polyphor Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Guest host Dr. Vamsi Velcheti, of the NYU Langone Perlmutter Cancer Center, and Dr. Brian Henick, of the Columbia University Herbert Irving Comprehensive Cancer Center, discuss advances in KRAS-mutated lung cancer in the KRYSTAL-1 trial, and the association of ctDNA with overall survival in the NADIM trial, as well as other key advances in lung cancer presented at the 2022 ASCO Annual Meeting.   TRANSCRIPT   Dr. Vamsi Velcheti: Hello, everyone! This is Dr. Vamsi Velcheti, I'm your guest host for the ASCO Daily News podcast, today. I'm an associate professor and medical director for the Thoracic Oncology Program at Perlmutter Cancer Center at NYU Langone Health. My guest today is Dr. Brian Henick, an associate director of the Experimental Therapeutics Program, and assistant professor of Medicine at Columbia University's Herbert Irving Comprehensive Cancer Center. We'll be discussing key abstracts in lung cancer that were featured at the 2022 ASCO Annual Meeting. Our full disclosures are available in the notes and disclosures of all guests on the podcast can be found on the transcripts at asco.org/podcasts. Brian, it's great to speak with you today. Dr. Brain Henick: Thank you so much, Vamsi, and ASCO Daily News for letting me join you to discuss these abstracts. Dr. Vamsi Velcheti: So, let's dive in. So, it's an exciting ASCO Annual Meeting. And I hope you had a great time at the Meeting. So, let's start off with the LBA9009 and KRYSTAL-1 clinical trial. The study showed the activity of adagrasib in patients with KRAS-G12C mutant non-small cell lung cancer and active untreated brain mets. So, what is the key takeaway from this trial? Dr. Brain Henick: Well, Dr. Sabari presented some encouraging data on this important population. As we know, patients with active central nervous system (CNS) metastases represent a population of unmet medical need who are often excluded from clinical trials. So, it's a credit to the investigators for including this cohort. As Dr. Sabari noted, and as Dr. Goldberg emphasized in her discussion of the abstract, the measured CNS penetration of adagrasib compares favorably with other CNS active compounds from other settings. The overall response rate was 35%, with a disease control rate of 80%. But impressively, the median duration of intracranial response and progression-free survival (PFS) wasn't reached. This certainly seems to be a CNS active compound, and we'll need to see how sotorasib stacks up in their comparable cohort. Ideally, we'd have randomized data to prove superiority over the standard of care, but we may be a few steps away from that. Dr. Vamsi Velcheti: So, Brian, in terms of CNS mets, how big of a problem is it in patients with KRAS G12C mutant lung cancers? Dr. Brian Henick: We know that CNS metastases are a big problem for G12C mutant lung cancer. The rates have been quoted as high as up to 42% of patients. And in particular, as you know, Vamsi, a lot of times trials often don't include, specifically, cohorts with active untreated brain metastases. And so, this is a very unique cohort in that sense. Dr. Vamsi Velcheti: I just want to highlight that we really don't know the differential efficacy of sotorasib and adagrasib in the CNS met population because the trials were CodeBreak 100 and other trials and data readouts from sotorasib did not include patients with untreated brain mets. We did, however, [see] CNS progression-free survival data that go in line with sotorasib. So, it's really important to see that data from sotorasib. Dr. Brain Henick: I definitely look forward to seeing that. Dr. Vamsi Velcheti: So, let's talk about Abstract 8501. The primary endpoint that was presented at ASCO [Annual Meeting] was the pathologic complete response to chemotherapy and nivo vs. chemotherapy as a new adjuvant treatment for resectable stage 3, a non-small cell lung cancer. This was the phase 2 NADIM trial. So, what do you think about this study? And what's your key takeaway from the study? Dr. Brain Henick: Dr. Provencio from Spain presented data from this randomized study as you said, of nivo plus carbo taxol compared to carbo taxol as neoadjuvant therapy for potentially resectable stage 3-A and B non-small cell lung cancer. So, I did want to compare this to the randomized data that we have from Checkmate 816, which interestingly allowed for earlier-stage disease as low as 1-B. And they also allowed for more flexibility in the choice of platinum doublet regimens. This study, NADIM 2, employs 2:1 versus 1:1 randomization, which we saw in Checkmate 816. Another important difference was that NADIM 2 required adjuvant nivolumab for 6 months in the study arm, whereas Checkmate 816 didn't include any immunotherapy in the adjuvant setting, but they allowed for a standard of care chemotherapy. In NADIM 2, the control arm didn't include any adjuvant therapy. In keeping with the impressive improvements over historical pathologic complete response rates of about 5%, this chemotherapy-IO regimen yielded a path complete response (CR) rate of 36.8%. It also showed a major pathological response, which again is defined as less than 10% viable tumor of 52.6%, and an overall response rate of 75.4%. So, it looks like there's a benefit that's happening upfront with the immunotherapy and chemotherapy as opposed to this just being an adjuvant phenomenon. This is also in keeping with data that we saw with Checkmate 816, as well as neoadjuvant atezo plus chemotherapy in the phase 2 study that was led by Catherine Shu and colleagues here at Columbia a few years ago. Overall, this is more encouraging data for the neoadjuvant use of immunotherapy. The earlier immunotherapy marches into the treatment course of patients with lung cancer, the greater the cost of toxicity. So, I think an important thing for us to focus on going forward is trying to develop strategies to better identify the patients that are most likely to benefit. Dr. Vamsi Velcheti: So, Brian, I think from a practical standpoint, now that we have approval for neoadjuvant immunotherapy and adjuvant immunotherapy, we have some practical challenges in terms of how we manage our patients. Of course, the new adjuvant is very appealing because it's only 3 cycles of chemoimmunotherapy, but the challenge though, is a majority of the patients don't have a CR, or a significant proportion of the patients have an ongoing response or significant residual disease at the time of surgery. So, the question then would be what do you do after surgery if they're having an ongoing response? Do you think 3 cycles of immunotherapy are inadequate systemic therapy for these patients? Dr. Brian Henick: It's a really important question, Vamsi. I think until the data is mature, we're just kind of limited by the extent of what the data tells us so far, and then we have to kind of do our best as the treating doctor to navigate the patient's situation. So, tools that we'd still have available to us in the adjuvant setting that are approved are things like chemotherapy and radiation, leveraging things like circulating tumor DNA, I think maybe a promising path forward, as well to help guide strategies there, but I think until the data is mature, it has to be highly patient-focused to figure out what seems to be most appropriate there. How are you navigating those situations, Vamsi? Dr. Vamsi Velcheti: Yeah, as you said, it is very challenging. I think we need more data. And of course, the challenge now is like, if you use immunotherapy in the new adjuvant setting, it's very likely you're not going to get insurance authorization for 1 year of adjuvant atezolizumab. So, we really need studies to optimize treatment paradigms here. As you suggested, maybe circulating tumor DNA (ctDNA)-based approaches to look at residual disease, I think, that would be one great way to do it. Let's move on to the next abstract, Brian. I found Abstract 9001 really interesting. It's a U.S. Food and Drug Administration (FDA) pooled analysis that looked at outcomes of first-line immune checkpoint inhibitors, with or without chemotherapy based on the KRAS mutation status and PD-L1 expression. So, what is your take on this abstract and how do you think this is going to impact our practice? Dr. Brian Henick: So, Dr. Nakajima and colleagues explored the observation from individual trials that patients with KRAS-mutant lung cancer seem to have better responses than wild type with immunotherapy (IO) alone. But the favorability of these responses seems to be abrogated with chemotherapy-IO. We know that KRAS accounts for 25% of oncogene-driven non-small cell lung cancer predominantly at amino acid 12. And with the emergence of direct inhibitors of G12C, understanding the clinical features of these tumors may be critical to inform optimal integration of this new class of drugs and also to make sure that we've optimized treatment algorithms for KRAS patients in general. So, this study's authors at the FDA pulled data from 12 registrational clinical trials that were investigating first-line checkpoint inhibitor-containing regimens and they found no significant difference between KRAS wild type and mutant for overall survival regardless of the regimen used. The best outcomes were seen with chemoimmunotherapy regardless of KRAS status. This retrospective analysis does suggest that the notion of there being lesser benefit from chemoimmunotherapy from Dr. Gadgeel's study might not hold up in the overall population, but I think it raises important questions, like, are all KRAS mutations alike? The absence of KRAS mutation status for a majority of patients included in these studies limits the interpretation of the data. And also, the absence of commutation status makes it a little harder to interpret. And other important questions remain such as how G12C inhibitors will factor in? What were your thoughts, Vamsi? Dr. Vamsi Velcheti: No, I completely agree with you, Brian. I think we need more data and we know that commutation status is a very important aspect in terms of KRAS-directed therapies. And of course, with a lot of promising data from these KRAS inhibitors, there's an interest in moving these drugs into the front-line therapy for patients with KRAS mutations. But I think it's going to be quite challenging to incorporate them into the front-line therapies and we clearly will need better characterization of these patients with KRAS mutant [lung cancer] to further personalize treatment in the frontline setting for these patients. So, let's move on to the next abstract. This is the lung map study, Abstract 9004. This is a study sponsored by the National Cancer Institute (NCI), the lung map study, looking at overall survival from a phase 2 randomized study of ramucirumab and pembrolizumab, what's the standard of care in patients with advanced non—small cell lung cancer previously treated with immunotherapy. So, what were your key takeaway points here from this study? Dr. Brian Henick: So first of all, it's very exciting to see data from this very ambitious long map sub-study yield a positive result. Whereas many of the arms of this study were biomarker-guided, Dr. Reckamp presented the results from pembro plus ramucirumab as compared to the standard of care in unmarked patients with non-small cell lung cancer who had progressed after prior treatment with chemotherapy and immunotherapy. The data seems to suggest that pembro plus ramucirumab may be better tolerated than the standard of care chemo-containing regimens, as the experimental regimen had fewer serious adverse events. Pembro plus ramucirumab had a median overall survival of 14.6 months as compared to 11.6 months in the control arm and this was statistically significant. The PFS difference wasn't significant, but there was a late divergence in the curves. Dr. Bestvina nicely summarized some of the study's limitations such as the mixture of control regimens used, and there were really interesting signals that were found on subgroup analysis, such as benefit in those with mixed histology tumors, STK11 mutant tumors, and those who received chemotherapy prior to immunotherapy. The subgroups deserve further attention in the future. For now, this regimen may be an appealing option as an alternative to chemotherapy for the right patients. What do you think? Dr. Vamsi Velcheti: Yeah, I agree, Brian. I think it's a really promising combination. We've always seen some synergy with VEGF inhibitors and immunotherapy in multiple studies and multiple tumor types. So, we really need to develop better ways to select patients for VEGF combination-based approaches in lung cancer. So, let's move on to another interesting study. This is Abstract 9000. This explores the outcomes of anti-PD-L1 therapy with or without chemotherapy for first-line, metastatic non-small cell lung cancer with a PD-L1 score of greater than 50%. So, this is an FDA pooled analysis. So, what were your key takeaways from this abstract? Dr. Brain Henick: I thought this question was really well suited for a large pooled retrospective analysis and our colleagues at the FDA didn't let us down here. The question really was what's the optimal approach for patients with non-small cell lung cancer with greater than 50% PD-L1 in view of the absence of direct comparisons between these arms in prospective studies? I thought one of the most striking findings from Dr. Akinboro's presentation was the dismally low rate of underrepresented minority patients that were included in these registration trials. As far as the findings for the patients who were studied, although the Kaplan-Meier curves for overall survival showed early separation, the difference wasn't statistically significant. Subgroup analysis revealed a trend towards better outcomes for immunotherapy alone among patients who are [age] 75 and above, suggesting that this may need to be parsed out as a unique population in subsequent studies. But in all, our equipoise as a field on whether to include chemoimmunotherapy-based first-line regimens should persist and should be guided, in my opinion, largely by clinical considerations. Can the patient tolerate chemotherapy? Do you need a rapid response? Are there other things that you thought in hearing all this, Vamsi? Dr. Vamsi Velcheti: Yeah, absolutely. I think I am still struggling with the decision of whether to add chemotherapy for patients with greater than 50%. To a large extent, it's actually a clinical decision. In some patients who have a large disease burden, I tend to kind of opt for adding chemotherapy to immunotherapy in the front-line setting. But of course, we need more data here. And this is actually a very helpful piece of information from the FDA. And as you pointed out briefly, Brian, I think the fact that there are very few underrepresented patients in the pooled analysis, I think kind of speaks to the need for addressing increased diversity in clinical trial accruals. I think this is a great segue to also talk about Abstract 9012, talking about disparities in access to immunotherapy globally. This is a study from India looking at 15,000 patients who were checkpoint inhibitor eligible and who have very low rates of uptake of immunotherapy. This is something that reflects the global team of the ASCO Annual Meeting talking about disparities and improving access to treatments in underserved minority populations here in the United States, and also globally, in the developing world, the disparities in terms of access to care are humongous. So, what are your thoughts, Brian? And also, if you could highlight some of the work that you're doing at Columbia about disparities, I think that would be great. Dr. Brain Henick: Absolutely! I think access to medications is a really humbling topic for those of us who are involved in developmental therapeutics, particularly with the transformational impact we've seen with the advent of immunotherapy over the last decade-plus. Dr. Ravikrishna's presentation is therefore extremely important. He described very low rates of uptake of immunotherapy by indication. And perhaps most strikingly, the discrepancy in uptake by patients' ability to pay for therapy with the vast majority of immunotherapy received by those who are private is very concerning. Even if the definition of restricted access was permissive, for example, I didn't see mention of the cancer stage as an eligibility factor, the fact that this represents a single referral center's data doesn't bode well for uptake elsewhere. So, I think we need to continue to work as a field on prioritizing strategies to help overcome these gaps, but good quality data such as this study is an important first step. And to that point, Vamsi, I'm very excited to be working with you in collaboration on an observational study for patients with lung cancer from underserved minority populations with lung cancer in New York City so that we can better characterize access to care, efficacy, and toxicity in this population. Dr. Vamsi Velcheti: Thank you, Brian. I'd really like to thank you for sharing your valuable insights with us today on the ASCO Daily News Podcast. We really appreciate it. Brian, thank you so much for joining us. Dr. Brain Henick: My pleasure. Thanks for having me. Dr. Vamsi Velcheti: And thank you to all our listeners for joining in today. You will find links to all the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcasts. Thank you so much.     Disclosures: Dr. Vamsi Velcheti: Honoraria: Honoraria Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline Dr. Brain Henick: None disclosed. Disclaimer: The purpose of this podcast is to educate and inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Dr. Brooke Worster and Dr. Nathan Handley of Sidney Kimmel Cancer Center – Jefferson Health shine a spotlight on cannabis use in palliative oncology.  They discuss guidance on dosing, legal concerns, and resources for oncologists with host Dr. John Sweetenham of the UT Southwestern Simmons Cancer Center. Transcript Dr. John Sweetenham: Hello, I'm John Sweetenham, Associate Director of Clinical Affairs at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center, and host of the ASCO Daily News podcast. Recent reports in oncology journals suggest that 20% to 40% of all patients with cancer use cannabis in some form during or after treatment to manage symptoms. However, a national survey of medical oncologists in 2018 found that 70% of oncologists did not feel equipped to make clinical recommendations regarding cannabis and only 46% recommended it clinically. Joining me to discuss cannabis use in palliative oncology are Dr. Brooke Worster, an associate professor and the director of supportive medicine at the Sidney Kimmel Cancer Center at Jefferson Health. And Dr. Nathan Handley, a medical oncologist and an assistant professor who is also at the Sidney Kimmel Cancer Center. Our full disclosures are available on our show notes and disclosures of all guests on the podcasts can be found on our transcripts and at asco.org/podcasts. Dr. Worster and Dr. Handley, thanks for coming onto the podcast today. Dr. Brooke Worster: Thanks for having us. Dr. Nathan Handley: Thank you. Dr. John Sweetenham: Dr. Worster, can you tell us how cannabis and cannabinoid-based medicines are used in palliative oncology and how prevalent this is? In addition, could you say a little about the use of cannabis in patients with cancer in the United States and how it compares with other countries? Dr. Brooke Worster: Yeah, absolutely. I think we are realizing more and more that cannabis or cannabinoid-based medications are used much more often than we as clinicians were aware. We just weren't asking our patients enough. And so, you mentioned other surveys about the kind of nationally sample representative of patients with cancer, we actually just also completed one that was a National Institutes of Health (NIH)-funded study, looking at cancer centers across the country and found similar rates that patients with cancer under the age of 65, at some point during treatment or survivorship, about 50% of them had tried cannabis. Interestingly, the largest growing segment of patients with cancer starting to use and inquire about cannabis are our [age] 65 and older patients. So, a quarter of them now report using it. And we actually found that 45% of patients over the age of 65 were interested but didn't feel comfortable having the conversation. Our country is kind of middle of the road in terms of what's accessible and what we use. Certainly, countries like Canada and some places in Europe, as well as Australia have a much more advanced marketplace as well as legislation and access to cannabis. And so, it's used more prevalently across kinds of the oncology spectrum, but there are still a lot of countries across the world where cannabis remains completely illegal. So, the United States is sort of in the middle. Dr. John Sweetenham: Thanks. You and Dr. Handley recently co-authored an article in the ASCO Daily News along with other colleagues. And in that, you write the patients most often want guidance about the formulation and dosing, which as I read your article seems to be somewhat elusive still, given the diversity and composition of the plant-based strains. You point out that understanding the onset of action and duration of effects are important first steps. Could you say a little bit more about this? Dr. Brooke Worster: Yeah, absolutely. I think when someone is trying this for the first time, or for the first time in years, understanding how and when they're going to feel the impact or the effects of primarily tetrahydrocannabinol (THC) but also cannabidiol (CBD) and other minor cannabinoids is important for them to be patient. We see that people that ingest either sublingual absorption or oral ingestion of products, don't recognize that it can take up to 60 to 75 minutes, even if you have other food in your stomach to really feel the effect. And then will kind of overdose in some ways or sort of re-dose and get more of an effect of the THC than they were looking for. Versus if someone is inhaling something, you're really going to feel that quite rapidly, right? Five minutes in terms of onset of action. The duration of effect for that is much less. You're talking 2 to 3 hours maximum for an inhalation form, versus 5 to 7 hours for something that's sublingual, or orally ingested. Dr. John Sweetenham: Thanks! Dr. Handley, we've read in your article and in others, that cannabis as a palliative treatment for patients is well-tolerated, safe, and an effective option to help them cope with malignancy-related symptoms. Can you comment a little on whether or not there is a downside to cannabis and cannabinoid use and whether there are negative interactions with other cancer treatments? And are there certain patients who should avoid the use of cannabis? Dr. Nathan Handley: I would say that in general cannabis can be very safe if taken carefully and appropriately, and ideally with some guidance from a qualified practitioner. But it is important to consider some of the risks and side effects that cannabis carries. So, I think the first point is that if smoked, or otherwise, inhaled, the smoke can have many of the same carcinogens that are found in tobacco smoke. It's also interesting because smoking of marijuana or cannabis and tobacco are highly correlated. And so, it can be difficult for us to kind of assess if there are increased pulmonary risks associated specifically with cannabis use compared to tobacco use. And there have been a number of large cross-sectional and longitudinal studies that haven't found this link between cannabis use and impaired pulmonary function tests or chronic obstructive pulmonary disease (COPD) or lung cancer. But there are still potential risks associated with inhalational forms. There's also some evidence that there may be higher cardiovascular risks among cannabis users, specifically in patients who have heavy cannabis exposure. So, there have been some studies that have looked at the role cannabis can play in thrombosis, inflammation, and atherosclerosis. There have been some case reports that have linked its use to myocardial infarctions and arrhythmias, cardiomyopathy, stroke, and arthritis. But those haven't necessarily been played out in large clinical trials yet. And so, essentially, if someone is at increased cardiovascular risk at baseline, if they're elderly, or if they have pre-existing cardiovascular conditions, these are things worth discussing with the patient. So, I wouldn't say that they're necessarily absolute contraindications. I think some of the more immediate side effects of cannabis are also worth discussing with patients. And these are often related to the amount or the concentration of THC that is present in the preparation. A THC ingestion can result in a number of adverse side effects. There can be impaired concentration, impaired spatial relationships, memory can sometimes be affected. And in some rare cases, you can have increased anxiety, paranoia, or even psychosis. And so, there are not again, strong studies demonstrating a distinct correlation between cannabis use and psychiatric disorders. This is an area that merits further investigation still, and those risks likely vary based on the type of the product, the potency, the composition, if it's synthetic, if it's illicit, but we do have some hesitation about using cannabis in patients who have severe pre-existing mental health conditions like psychosis or schizophrenia, or something like that. On the issue of interactions with certain cancer treatments, I think one thing that patients often wonder is if cannabis can be used to treat cancer? And there is some interesting in vitro data and some in vivo data to suggest that cannabinoids can modulate tumor growth. But the data here is very limited. And so, really what we say is that more research needs to be done in this area. I think the other area of interest is there's some preliminary data, suggesting that patients who are on immunotherapy may have a reduced response to that treatment if they're taking cannabinoids, but these data are also very early. And so, we don't make any clinical decisions based on it at this point. Dr. John Sweetenham: Okay. Thank you. Another area, which I think is concerning certainly to some oncologists and other physicians is the legal issues surrounding the use of medical cannabis. And the core issue there, of course, is the contradiction in many cases between federal and state laws. Dr. Worster, can you tell us a little bit more about this and how oncologists can inform themselves of these issues and perhaps feel a little bit more comfortable about prescribing or recommending medical cannabis? Dr. Brooke Worster: Absolutely. I think at the crux of this issue, you're spot on. I mean, it's muddy. And if you look at the map of our country, the state-by-state variation changes year to year. So, I think one of the biggest things for all clinicians to recognize is that there have been challenges to the legality of recommending, we're not prescribing because that is still federally illegal, but certainly recommending cannabis to patients. There have been legal and court challenges that have worked their way up to federal courts, and have always supported that this is a right to free speech and well within your protected rights as a clinician to have a conversation with your patient along the lines of all kinds of other lifestyle choices we talk about with patients. So, there's no risk in terms of having the conversation, per se, or guiding patients into the space. Where I would tell people to familiarize themselves is really the intricacies of your own state's laws, as well as where a patient may be living if you're seeing them across state lines. One really great resource for this is the National Consortium of State Legislatures. They do a very good job and keep very up to date on a state-by-state basis in terms of what's legal, what conditions, how to access it, if there's reciprocity between states or not, if you can bring product across state lines, who can access it, all of the things that our patients are concerned about, and thus, bringing very valid questions to us that we want to be able to kind of help support them in this conversation. Dr. John Sweetenham: Yeah. Thank you! You know, another issue that you do bring up in your recent article is that of pain management, which of course is a very important component of cancer care in general. But studies in the Journal of Clinical Oncology and elsewhere have recently found there's been a sharp decline in access to opioids among patients with terminal cancer, and some patients have had to turn to hospital emergency departments for pain control. The decline in access has been in part a response to the opioid crisis in the U.S. But do you think this raises an important question about whether we're doing enough to proactively address pain management with some of our patients, Dr. Worster? Dr. Brooke Worster: That's always a really important conversation that we aren't talking about enough. I think, truly, certainly, the pendulum has swung very far to the other side. And in some ways, this is beneficial, because as more and more of our patients with cancer are living into survivorship, we have certainly seen where iatrogenically, we have created dependency and substance misuse issues in the past, and it continues to happen. But I think that we need better ways to have honest conversations with our patients about both. What nuances to their pain exist? Pain is not pain is not pain, right? So, the etiology of their pain is important. And the way that we treat it shouldn't all be the same—neuropathic versus visceral versus a post-operative or inflammatory type of pain certainly should be looked at differently. I think access to opioids is critical for patients with cancer, although it really shouldn't be the only tool in our toolbox. Some of the work that we've done recently, it's interesting. There remains a wide racial gap in terms of access to opioids, as well, as we know this but less well-controlled pain in certain groups of patients with cancer, primarily minority Black and Hispanic patients versus White counterparts. And some of that has to do with the underlying responsiveness to opioids for various people, but also, how much are we talking about it? How much are we having the conversation? Is cannabis a helpful adjuvant, there? Are opioids something that are helpful? It should be talked about and continually readdressed. Dr. John Sweetenham: Thank you. Dr. Handley, Dr. Wooster just mentioned there in her previous comments, the issue of having honest conversations with our patients in the realm of pain control. But on a broader kind of perspective, do you have any recommendations on how to broach conversations with patients about cannabis use as a potential option for symptom management? Dr. Nathan Handley: Yeah, I think that's a really important question. These can be very difficult conversations. Cannabis use is something that is socially, culturally, and regulatory charged. It's very complex. And so, it can be a challenge to have these conversations. I think some general principles about how to effectively engage others, whether they're patients or friends or colleagues can be really helpful. So, I often reflect on this dictum from Stephen Covey, who is the author of this book called, The Seven Habits of Highly Effective People. In this book, he describes the fifth habit as being, “Seek first to understand then to be understood.” So, basically, what he's saying is if your goal is to motivate others, you have to understand where they're coming from before you can meaningfully affect their behavior. So, this sentiment is really a core principle behind the technique called motivational interviewing, which can be very useful to help motivate behavior change in patients and understand where patients are coming from, at the start of a conversation even. So, this technique is really built on 4 foundational principles. And those are acceptance, which is essentially empathizing with the patient, recognizing that they are an important participant in their own care. They're really the driver of their own care. Compassion, which is really emphasizing the well-being of the patient first and foremost. Collaboration, which is partnering with the patient, and not necessarily having a paternalistic relationship with them. And then curiosity, which is about understanding a patient's behaviors and motivations in a non-judgmental way. And so, I think this is really important because it can lead to openness when having a conversation with a patient. So, this has been summed up more simply as “Don't tell. Ask.” So, the idea with motivational interviewing, is you need to be open to understanding where a patient is, and this approach can be taken with 4 steps. So, first, you, you just listen, there's interesting data about how clinicians and physicians spend a lot of time talking in interactions with patients, and not as much time listening. And then we may have a tendency to jump in very quickly and be uncomfortable with silence. And so, this is just a real opportunity to just be open to patients and hear them to understand what pre-existing perceptions they may have. And so, it's hard to have a conversation with a patient about cannabis, if you think that they are going to be very open to it. And it turns out that 5 minutes into the conversation, they have some really deeply held reservations about the use of cannabis. So, first, you engage and listen to them to understand where they're coming from. And then you can focus. You can focus specifically on what the patient's goals are with respect to treatment, with something—in this case with cannabis. What are they hoping to get out of it? Is it improved pain management? Is it some other symptom that they're seeking? And then you can kind of evoke, this next step is evoking what their motivations are? Why do they want to improve this particular component of their treatment? Why did they want to feel better in this way? What are they hoping to achieve? And then, once you've kind of gotten through that groundwork, you can then plan together about how best to approach, in this case, cannabis use, in a way that is mutually agreeable, you can come to a plan together. And this approach epitomizes the concept of shared decision making where this is a conversation that happens together and between 2 people with the interest of the patient kept, first and foremost. Dr. John Sweetenham: Great advice. Thank you! Dr. Worster, just before we close up, you did mention earlier 1 potential resource for oncologists who need guidance on how to safely use cannabis for palliative pain management. Do you have any other recommendations in terms of resources that can be helpful to them? Dr. Brooke Worster: Yeah, absolutely. I wish there were a lot more here. And truth be told, we're still working hard to certainly develop the body of research and then disseminate it in terms of education. But if people are interested, there are increasing amounts of continuing medical education (CME) options that are out there. Each state that has medically legal or medically approved cannabis use on their state websites will have recommended or required depending on which state, I practice in Pennsylvania, and there are required CME courses that you need to take. But all of the states have different ones that are either recommended or required, and that's certainly an easy place to start in terms of some quality education. Thanks to the work that you and others are doing. I think it's certainly coming out through various oncology publications and multimedia access and things like that. And we also have, and some other academic centers around the country now have, online certificate and Master's programs that if people are really interested, they can kind of dive in and take courses or even get a certificate in cannabis medicine or cannabis science, things like that, to help them feel a lot more educated and informed. Dr. John Sweetenham: Well, I'd like to thank you both for sharing your insights with us on the podcast today. And also, for the valuable research that you've been doing on this topic. This is something that I'm sure is going to gain increasing importance to us all in elevating the awareness of this among the oncology community is really important. Thank you for the work that you're doing. Dr. Brooke Worster: Absolutely. Thank you for having us. Dr. Nathan Handley: Yes, thank you. A pleasure! Dr. John Sweetenham: And thank you to our listeners for your time today. If you're enjoying the call sent on the ASCO Daily News podcast. Please take a moment to rate, review and subscribe wherever you get your podcasts.     Disclosures: Dr. John Sweetenham: Consulting or Advisory Role: EMA Wellness Dr. Brooke Worster: Consulting or Advisory Role: Ethos Cannabis (Inst), PAX Therapeutics Research Funding: Ethos Cannabis (Inst) Dr. Nathan Handley: Research Funding: Nektar Therapeutics (Inst) Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.        

Guest host Dr. Fumiko Chino, a radiation oncologist at Memorial Sloan Kettering Cancer Center, leads a discussion on how the continual improper aggregation of Asian American (AA) and Native Hawaiian and other Pacific Islander (NHPI) populations downplays cancer disparities with Dr. Scarlett Lin Gomez, a professor in the Department of Epidemiology and Biostats at UCSF Helen Diller Family Comprehensive Cancer Center, and Dr. Kekoa Taparra, a radiation oncology resident at Stanford University.   Transcript Dr. Fumiko Chino: Hello, I'm Dr. Fumiko Chino, a radiation oncologist and Health Equity researcher at Memorial Sloan Kettering Cancer Center, and the guest host of the ASCO Daily News Podcast today.  In today's episode, we'll explore the unequal burden of cancer across diverse communities, specifically looking at how the continual improper aggregation of Asian American, Native Hawaiian, and other Pacific Islander populations mask cancer disparities.  Joining me for this discussion are Dr. Scarlett Lin Gomez, a professor in the Department of Epidemiology and Biostats at the UCSF, Helen Diller Family Comprehensive Cancer Center, and Dr. Kekoa Taparra, a radiation oncology resident at Stanford University.  My guest and I have no conflicts related to our topic today. Our full disclosures are available in the show notes and disclosures for all guests on the podcast can be found on our transcripts at ASCO.orgpodcasts. We've all agreed to go by our first names. Scarlett and Kekoa, it's great to have you on the podcast today.  Dr. Scarlett Lin Gomez: Thank you so much. Great to be here.  Dr. Kekoa Taparra: Thank you.  Dr. Fumiko Chino: I'm so excited to start. My first question is just really general, which is can you describe your background, how you got into this research and why it's really meaningful for you and your community.  I can start just a little bit with myself. I'm Japanese American, my grandfather came to the United States before World War II and was actually excluded from coming into the United States under the Asian Exclusion Act.  He managed to come into the country walking up from Chile, ultimately started a farm in the United States, but was interned during World War II under Executive Order Act 9066. And he and my father and the family suffered some hardships from that but managed to rebuild.  I think kind of overall, I've been interested in how Asian communities and groups within Asian America and other race and ethnicity groups have had differing experiences within the American history and within American health, and specifically within cancer. Scarlett, can you go ahead and tell me just a little bit about yourself?  Dr. Scarlett Lin Gomez: Absolutely. I think that we find amongst ourselves who identify as Asian-American, Native Hawaiian Pacific Islander, that many of our unique experiences, life experiences, do have an impact on the cancer research that we do today.  I am a first-generation Taiwanese American. My family came over after the repeal of the Asian Exclusion Act in the early-mid-70s. Like many Asian American families, we settled where we already had some family here in the United States, and so that happened for us to be in central Washington state.  I grew up in central Washington, a very largely rural homogeneously non-Hispanic White population, and went to school largely in Spokane, Washington. So, eastern Washington.  During my time growing up there, I certainly, and my family had experiences with structural racism. I definitely saw firsthand among my family and our social networks cancer as a very strong cultural stigma.  For example, my grandmother's colorectal cancer diagnosis was actually never disclosed to her. In fact, this is very common among many Asian cultural populations. I also observed firsthand the relevance of our neighborhoods, our neighborhood environments, our social environments, and the structural context within which we live, work, and play, and how that really has a strong impact, not only on our access to health care but health behaviors and degree of social connections.  I then moved to the San Francisco Bay Area. You can certainly imagine the vastly different cultural and structural and neighborhood environments of that in the Bay Area compared to growing up in central and eastern Washington.  This is in fact—little to my knowledge—actually largely shaped the area of research that I chose to go into. In my doctoral dissertation, I had the opportunity to be introduced to and become involved with working with cancer registry data.  I was actually surprised to learn that in fact, within Cancer Registry data, there were some several dozen codes for distinct Asian American, Native Hawaiian, [and] Pacific Islander ethnic groups, yet for me, it was surprising: why don't we see any statistics by these specific ethnic codes?  In fact, we continue to see statistics for the Asian American population, Asian American Pacific Islander population aggregated as a whole. So, I set out for my dissertation to understand a very non-sexy doctoral dissertation topic to understand the quality of that data and how can we get the data to a point where we could start to report on statistics for disaggregated populations. That has really become a whole research program for my group today.  Dr. Fumiko Chino: It's so nice to hear the history of how you got into that and even just if you had happened to end up in New York City, maybe your research could have gone a different direction. Kekoa, can you tell me a little bit about your history and what brought you to do the research that you do today?  Dr. Kekoa Taparra: Yeah, absolutely. I am part Native Hawaiian from both my mom's and my dad's side. And just as a note, when we say Native Hawaiian, it's not the same as saying, native Californian or native Texan. That's not what I'm talking about. I'm indigenous Native Hawaiian, from both my mom's and my dad's side.  I actually had the good fortune to attend the Kamehameha schools. That's a school for indigenous Native Hawaiian youth in Hawaii.  And so, I grew up learning a lot about our history or culture throughout the Pacific, from Melanesia to Micronesia, and Polynesia. And so, with that kind of sense of identity, I really got a grasp of our community and our community's needs. And within my own family, I've had 10 family members, all of whom were Native Hawaiian, all die from cancer.  That was something that I grew up with just thinking that cancer was just something that people couldn't overcome. It wasn't really until college that I got really interested in research, and that led to my eventual attending of Johns Hopkins. I was in the lab of Dr. Phuoc Tran, who was an MD, PhD, radiation oncologist, and he was really the first to bring me into the clinic and I'll never forget, the first time he ever told the patient, “Let's cure your cancer.”  That was just something that I'd never heard before, given all my family members really struggled with different types of cancer diagnoses, none of them had the same thing. And so, really, from that point on, that's what inspired me to go to medical school. And towards the end of my medical school years, when I was actually applying for radiation oncology, I was a true bench scientist, and I'm a lab rat—that's where I've always belonged and felt like I belonged. But towards the end of medical school, when I was interviewing for radiation oncology, I met one of my mentors, Dr. Curtiland Deville Jr., at [Johns] Hopkins.  He was really the first to, at least through my application, recognize the kind of cultural and historical context of what I've been through, what my family and my community in Hawaii, we call lāhui, what our lāhui has gone through. And so, he really encouraged me to write about it.  That's kind of how I've ended up in this niche of speaking on Pacific Islander health. Again, just full disclosure, as a part Native Hawaiian, I can't even speak for the whole lāhui. I'll speak for myself and what I know.  Again, the Native Hawaiian lāhui is very different from the rest of the Pacific Islands. But overall, I do research Pacific Islander health.    Dr. Fumiko Chino: I love having both of you on this podcast because I feel your voices are so unique, but again, you also represent sort of different ends of the spectrum in terms of your research career, someone who's a little bit more senior and someone who's more junior.  I think that really gives us a well-rounded perspective. Scarlett, can you tell me just a little bit about the history of Asian American, Native Hawaiian, and Pacific Islander aggregation and why it might be a problem?  Dr. Scarlett Lin Gomez: I honestly don't know why the data are aggregated for. We're talking about people who come from 30 different countries and speak more than 100 different languages.  My guess is that historically, we have tended to aggregate because of convenience, but potentially also just lack of knowledge about the vast heterogeneity among these populations.  And so, I think for us who do research in this field, our hope is that by continually putting out the data that we can start to educate folks about why it is harmful, in fact, to aggregate.  Why is this a problem? I think that we hide disparities. In fact, if you look, I think part of the reason why the practice of aggregation has continued is because when you look at the aggregated statistics, with regards to cancer, it actually paints a very rosy picture for the most part, for most cancer statistics that we look at.  That's because the data are largely based on the largest groups, statistically the largest groups of those who potentially have been here the longest, but in fact, when we disaggregate, we know dramatic heterogeneity, as we would expect, because we know socio-demographically and based on immigration patterns and language patterns, these populations are really different.  So, we would expect, in fact, we do see that translate into differences in cancer outcomes. I will give a direct answer to your question about why this is a problem. I like to note the very poignant story of Susan Shinagawa, who is a Japanese American woman who was diagnosed with breast cancer. She's also my friend and colleague, and she was one of the first advocates who really inspired me in doing this research.  And so, her story is that she had to go to 3 different surgical oncologists to finally have her very prominent breast lump biopsied and looked at. She will recall that the reasons why she had to go to all these different surgeons was because they continuously told her, “You can't have breast cancer. You're Asian, and you're too young. Asian women don't get breast cancer." Her story isn't unusual.  I think the other harm in aggregation is that the community then thinks that our risks of cancer are low and that this doesn't affect us, and in some of the first publications we put out, there was a paper where we documented both high survival rates among Asian immigrant women, as well as high rates among young Asian American women for breast cancer. This was published in the American Journal of Public Health in 2011.  I actually received personally several emails from Asian women out in the community saying, because we had received quite a bit of press, this was reported out in the media, and they noted to me that they themselves were shocked when they were diagnosed with the disease because they thought that this was a “white old woman disease.” But in fact, it's not.  I have a strong family history of breast cancer, as many of us do, and other cancer sites. And so, I think that perpetuates not only the model minority myth but the cultural stigma of cancer as a disease.  Dr. Fumiko Chino: I can't wait until those oncologists that passed her by find out about the history of lung cancer in young Asian American women.  Scarlett, can you talk a little bit and I know you had mentioned this before, in terms of when you first started digging into some of the data, how challenging this research can be in terms of, for example, do every databases have granular data in terms of the Asian races and countries of origin, ethnicities?  Dr. Scarlett Lin Gomez: I think it's incredibly challenging and as an epidemiologist, we need the data. That's if we don't have the data, we don't even have a place to start. I think we've been fortunate to some extent within the cancer space in that the major databases that we really rely on to report the burden of cancer among our various groups do, in fact, have a fairly good capture of detailed Asian American, Native Hawaiian, and Pacific Islander codes, yet there is much that can be improved. The information on place of birth, for example, is really incomplete.  Also, our group has really started working with data from electronic health records. And that is highly variable in terms of data capture availability, the granularity of codes, and the availability of the relevant variables like birthplace and language across the different groups.  So, I do firmly believe, and I would call to action that I think we need to make a concerted effort to improve the granularity of data that are being collected.  I think the other challenge that has really come about is the small data problem. I think that our epidemiologic and clinical toolbox is very limited in terms of what we can do, analytically with small populations. But I would put forth that just because a population is small in numbers doesn't mean that they're any less important.  And so, I think that we need to do better in terms of developing better methodological and statistical approaches to being able to not only quantify but understand the burden of cancer in all of our populations.    We also need better approaches to begin to study the intersectionality of multiple marginalized social determinants, statuses, language, and ensure language inclusion in terms of really being able to adequately study and incorporate and include these populations.  Dr. Fumiko Chino: Can you talk specifically about some of the disparities that you've actually uncovered with your research? What are we talking about when we say that aggregation masks disparities? If I just say, Asian Americans are doing great from a cancer standpoint, what am I missing?  Dr. Scarlett Lin Gomez: One particular disparity I can certainly highlight is the high burden that we recently documented in a publication last year in the Journal of National Cancer Institute that documented the high rates of lung cancer among certain groups of Asian-American, Native Hawaiian, and Pacific Islander females who have no history of smoking.  Ours was the first study to actually show what the rates of lung cancer are in these particular groups. And it's particularly high—1.5 to 2 times higher among some of the Asian American, Native Hawaiian, and Pacific Islander groups compared to non-Hispanic White female never smokers.  When we look across the Asian American, Native Hawaiian, and Pacific Islander ethnic groups, we note that there are differences in that risk. One example is that among Chinese American females 80% who have been diagnosed with lung cancer have no history of smoking, the vast majority, 80% have never smoked, in contrast to smaller percentages among, for example, Native Hawaiian and some Pacific Islander groups.  Another pattern in terms of heterogeneity is that we actually did not notice the higher rates of lung cancer among Japanese American female never smokers. And this is an interesting observation, we actually note similar patterns for Japanese American women for breast cancer as an example, and this is something that definitely needs further follow-up.  In fact, we're conducting a study right now called “FANS: Female Patient Never Smokers,” which is the first study to try to identify genetic and epidemiological risk factors for lung cancer among Asian-American females who have never smoked.  Dr. Fumiko Chino: Kekoa, can you speak about what your research has shown?  Dr. Kekoa Taparra: Yeah, definitely. From the perspective of a recent paper that we published in the JAMA Network Open, we looked specifically at the Hawaii Tumor Registry looking at patients in Hawaii, who were treated for premalignancy, the DCIS (ductal carcinoma in situ).  What we found were the patients who ended up developing a second breast cancer after being treated for that first DCIS [that] the rates of the second malignancies both from ipsilateral and contralateral breast cancer were primarily seen in Native Hawaiians. Also, to some extent, Filipinos as well compared to other Asian ethnic groups.  I think that there are definitely some trends that we continue to see in terms of who might potentially be at higher risk, but in other work that we have presented at [2021] ASCO Quality Care Symposium (Abstract 80) with yourself, we found that in terms of it in things like overall survival, there are potential differences in terms of Native Hawaiian and other Pacific Islanders as well as even Southeast and East Asian groups.  And so, I think there's a lot of work to be done in terms of what are the kind of implications for disaggregation? What are appropriate techniques for data disaggregation? What is too much to disaggregate because we can disaggregate for a Native Hawaiian female who is from a specific zip code and who never smoked, and like, is that kind of the data disaggregation that we end up wanting, or is there something a little bit broader, that still tells us the same story of who should we be paying attention to?  And so, I think there are a lot of unanswered questions. I think that Scarlett is doing amazing, amazing work that I continually follow. So, I think there's a lot to be done still.  Dr. Fumiko Chino: So, I guess that leads to my next question, which is the concluding question, which is, what is the next step? So, how do we either: get better data or how do we actually intervene?  So, Scarlett, I know you had talked a little bit about the FANS study. Can you talk a little bit about your breast cancer cohort study in terms of really thinking about getting together diverse data sets and making sure that it's powerful enough to actually draw some conclusions?  Dr. Scarlett Lin Gomez: Absolutely. Breast cancer is actually a really interesting disease that I think we are in the midst of seeing a very interesting and dynamic pattern of breast cancer.  We actually noted recently, in a small study in the Bay Area, that we may be seeing a reversal of higher rates among Asian American immigrant women compared to those who were born here. I think actually, this makes sense.  If we think about, especially in the San Francisco Bay Area, who were the immigrants over the past 10, 20, and 30 years. And in fact, we are seeing very high, rapidly increasing rates of breast cancer within many of the East Asian countries.  And so, I think we are really undertaking work to try to understand what some of these patterns are, but I think we are really well-positioned to invest in cancer research among Asian Americans, Native Hawaiian, and Pacific Islanders, because of these dynamic patterns, and the vast heterogeneity that we know exist within these groups.  I think that investing in research among these groups can really tell us a lot in terms of the discovery of novel risk factors. My last final thought would be to the funders out there to really think about what we can learn by focusing on these populations, but also being able to study the disparities that really have gone ignored for a long time.  Dr. Fumiko Chino: Kekoa, can you talk about some research that you have coming up that may or may not have recently been funded?  Dr. Kekoa Taparra: Absolutely. One of the things I definitely have to appreciate from ASCO is having the opportunity to kind of publish our work in JCO Oncology Practice on a paper with the historical context of Native Hawaiian and other Pacific Islanders with cancer.  Actually, a recent project that I have had, and I've been working on for the past year, really came about from a physician out actually in Micronesia, who read the paper and then contacted me, and this is a project specifically on betel nut induced oral cavity cancer.  Betel nut is something that is consumed throughout the Pacific Islands as well as Southeast Asia, but something specific to islands in Micronesia is that according to the WHO (World Health Organization), they have the highest rates of elementary and middle school students who consume betel nuts.  So, they had a very, very concerning epidemic right now of betel nut-induced oral cavity cancer. And so, one of the projects that I've been working on is a clinical trial, which we're calling NEO-CORAL. But the trial is specifically looking at a neoadjuvant immunotherapy approach to local or regionally advanced betel nut-induced oral cavity cancer.  We're really excited to be working with teams from Guam, which is in Micronesia, as well as Queen's Medical Center in Hawaii, where I'm from, and at Stanford as well. And this tri-site approach we're hoping to kind of conduct a culturally careful and culturally aware clinical trial so that we can really try and make a difference in these patients' lives because the biology and just the aggressiveness are nothing like we've ever seen with tobacco-induced oral cavity cancer alone.  I'm really grateful for certain funders that we've had recently who have funded this grant. I think it really just goes to show the kind of excitement around really helping a very marginalized community.  Dr. Fumiko Chino: I think that that study and I think putting in the context of what Scarlett just said in terms of, we need this data, we need granular data, we need funding so that we can actually design interventions that are really tailored to unique, vulnerable communities to really provide the resources, education, and culturally competent care that actually gets people the best outcome so that there are not haves and have-nots in terms of health care, and that's really again everyone's goal.  I'm wrapping up now. I really like to thank Dr. Scarlett Gomez and Dr. Kekoa Taparra for sharing your really valuable insights with us today and for your dedication to addressing the unequal burden of cancer across diverse communities.  Dr. Kekoa Taparra: Thank you.  Dr. Scarlett Lin Gomez: Thank you.  Dr. Fumiko Chino: Thanks to our listeners for your time today; you will find links to all of the studies and presentations discussed today in the transcript of this episode. And, if you're enjoying the content of the ASCO Daily News podcast, please take a moment to rate, review, and subscribe.    Disclosures:  Dr. Fumiko Chino: None disclosed.  Dr. Scarlett Lin Gomez:  Employment: Bioinspire (Immediate Family Member), Valentia Bioanalytics (Immediate Family Member)  Stock and Other Ownership Interests: Amgen (Immediate Family Member), Bioinspire (Immediate Family Member)  Consulting or Advisory Role: GRAIL  Page Break  Dr. Kekoa Taparra: None disclosed.  Disclaimers: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product service organization, activity or therapy should not be construed as an ASCO endorsement.   

Dr. Arjun Gupta, a GI medical oncologist at the University of Minnesota Masonic Cancer Center in Minneapolis, speaks with host Dr. John Sweetenham, associate director for Clinical Affairs at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center, about the concept of time toxicity in cancer treatment. Dr. Gupta proposes a measure of time toxicity and a framework for how it could be implemented in research and clinical practice.   Transcript Dr. John Sweetenham: Hello, I'm John Sweetenham, the Associate Director for Clinical Affairs at UT Southwestern Harold C. Simmons Comprehensive Cancer Center, and host of the ASCO Daily News podcast. I'm delighted to welcome Dr. Arjun Gupta to the podcast today. He's an assistant professor and gastrointestinal medical oncologist at the University of Minnesota Masonic Cancer Center in Minneapolis. We'll be discussing the concept of time toxicity and its relevance for patients with cancer, especially those with advanced cancer who face treatment decisions in the context of limited time. Dr. Gupta will share his insights on how to measure time toxicity and discuss a framework for how it could be implemented in research and in clinical practice. My guest and I have no conflicts relating to our topic today. Our full disclosures are available in the show notes and disclosures of all guests on the podcast can be found on our transcripts at asco.org/podcasts. Dr. Gupta, it's great to have you on the podcast today. Dr. Arjun Gupta: I'm an avid listener of the podcast. It's a joy to be here. Dr. John Sweetenham: Thank you. It's a joy to have you on the podcast as well. We're particularly pleased to have you discuss this important topic that you and your co-authors addressed recently, in your commentary in the Journal of Clinical Oncology. Can you first explain the concept of time toxicity, particularly as it relates to cancer treatment? Dr. Arjun Gupta: Yes, we conceptualize time toxicity as the time spent in pursuing a treatment for cancer. Now, this includes time spent in coordinating treatments, in travel to treatments, in waiting rooms, in actually getting that treatment, in getting anticipated and unanticipated adverse events, follow up tests and rehabilitations, frequent visits to a health care facility, all of this time that a patient and their care partner are spending is what we think of as time toxicity. This concept of time toxicity is perhaps applicable to all patients but is perhaps most applicable to people with advanced solid tumors, who are facing treatment decisions in the context of limited time. And in some cases, the overall survival benefit, or the time benefit offered by treatment may actually be overtaken by the time spent in pursuing that treatment. So, that's how we came up with this concept of time toxicity. Dr. John Sweetenham: Thanks. In your article, you propose a measure of time toxicity provides a framework for how it could be implemented in research and in routine clinical practice. Can you tell us a little more about this? Dr. Arjun Gupta: The measure we describe and propose is days with physical health care system contact. This is the measure of time toxicity that we propose. So any day in which a patient has any contact with the health care system, whether that be for a 30-minute blood draw, whether that be for a 3-hour procedure, whether that be for a 6-hour chemotherapy infusion, a 12-hour visit to the urgent care center, or an overnight stay is treated the same. It's a day with physical health care system contact. And we recognize that not all of these are the same but for the patient and their care partner, these often represent that an entire day is lost. As a corollary, days not spent with health care contact are home days. So, in essence, your overall survival or the time from diagnosis to death is nothing but the sum total of time toxicity or days with health care system contact and home days. Now me and my mentors, Dr. Chris Booth, and Dr. Elizabeth Eisenhower spent a lot of time thinking about whether we should propose a metric at all, or wait for the science to be advanced even more. But there are a couple of reasons we decided to go forward and propose this metric. Even though there are some deficiencies that I'll come to. First of all, this metric recognizes that oncology care is delivered in multiple settings. It's delivered infrequent trips to the outpatient clinics and infusion centers, and patients often require inpatient admissions for rest and rehabilitation. My mentors, Dr. Chris Booth and Dr. Elizabeth Eisenhower, and I discussed long and hard whether we wanted to propose a metric or wait for the science of time toxicity to progress. Ultimately, we decided to propose this metric because it's practical and can easily be measured. It is patient-centered, which is perhaps the most important thing. And third, it recognizes that cancer care is delivered in multiple settings, both inpatient and outpatient. There are a couple of things that we need to keep in mind while thinking about this metric. The first is that people with cancer are often sick because of underlying cancer and cancer care and physical health care system contact by itself is not a bad thing. So, we need to separate the additional time imposed by a specific cancer treatment over and above the time toxicity of cancer itself, and we also need to keep in mind that this metric has some limitations in that decreased health care contact or decreased time toxicity could represent poor access to care and could widen disparities in health care access. Furthermore, care is increasingly being delivered in the home of patients. And while that may decrease time toxicity, and may be more comfortable for certain families, for unprepared families, this may be very burdensome. So, we recognize that this metric is not perfect but we hope that this can at least start conversations about time toxicity, to fulfill our ultimate goal for clinical trials to actually report time toxicity alongside more traditional endpoints. Dr. John Sweetenham: Yes, I think one of the things that really struck me from reading your commentary was the fact that of course, for a patient, a 1-hour or 30-minute trip to the laboratory for a blood draw can disrupt the whole day. And in many respects, that can be as disruptive as spending 12 hours in the emergency room from a family and caregiver perspective that really kind of sank home with me, I must say, having read the commentary. On that note, you know, could you give us some specific examples to show how time toxicity negatively impacts patients? Dr. Arjun Gupta: Yes, so for a couple of trials that we described in the paper, we demonstrated that the time toxicity associated with pursuing the treatment was actually more than the average survival benefit offered by the treatment. Now we have to keep in mind that traditionally, oncology clinical trials don't report time toxicity. So, this was my co-authors and myself getting together and getting a best-case scenario from clinical trial publications. But as an example, for people with advanced biliary tract cancers, or cholangiocarcinoma, in the second line, there was a recent trial that demonstrated that FOLFOX chemotherapy, on average, improved survival by 27 days. And we demonstrated through the trial level publication, that for the average patient who was getting the average number of chemotherapy doses, coming in for blood work, coming in for scans, coming in for oncology assessments, that for the average patient, the time toxicity was more than this 27-day benefit, it was 30 days. And so, this is a very clear example of a patient who potentially loses more time than what they gain. It's very important to recognize that patients may value these decisions differently, and we're not saying that this treatment is bad or should not be pursued. People have different values, and we should explore that, but the biggest issue right now is that oncologists don't have the data from clinical trials to even have these conversations with patients. Dr. John Sweetenham: Thanks. And so, I'll pick up on that point. Obviously, the literature is very full of studies that have looked at oncologists and their skills for wanting a better word at having the end-of-life discussions and goals of care discussions with their patients. Do you sense that there is or will be a reluctance on the part of oncologists to have these kinds of conversations about time toxicity for patients who may be nearing the end of their lives? Dr. Arjun Gupta: I don't think so at all. I will share that I've become much more humble since I've become an oncologist myself, and I've become less critical of oncologists. I think our jobs are incredibly difficult. And most, if not all, oncologists want to do the right thing and have these conversations. The 2 things that are missing right now are data. So, we just don't have the data, which is why we wrote this commentary as a call for clinical trials to report this. And the second is our own time toxicity or delay limitation of time in the clinic. A wise person recently said that the biggest technological advance in medicine will be more time with patients. So, I think we need more data on time toxicity and we need more time for ourselves with patients to have these conversations to help them reach the best decision for their own goals and values. Dr. John Sweetenham: Are there any other key takeaways that you would like to share with our listeners today? Dr. Arjun Gupta: I feel—yes. As the next steps, our team is looking at doing secondary analyses of completed clinical trials to show that using this metric of days with physical health care contact is feasible, even in the secondary analysis of clinical trials. While we advocate for this to be included prospectively in clinical trials. It's very important to note that in retrospective work, looking at time toxicity, we remember that the time toxicity of a treatment retrospectively represents not just the treatment itself, but the entire health care delivery system, and social determinants of health. So, we shouldn't get too far ahead of ourselves in interpreting treatments against each other. But that perhaps offers us an opportunity to look internally at ourselves and add our processes to see how we can improve. Lastly, there are several quality improvement initiatives going on to reduce time toxicity for patients, such as triage, and decreasing waiting room times, and we should perhaps advocate for and promote such work more broadly. Dr. John Sweetenham: Thanks so much, Dr. Gupta, for coming on to the podcast today and for sharing your thoughts on a subject, which I'm sure is going to be something that will provoke a lot of discussions and will make many of us think harder in the future. And we look forward to seeing your ongoing research in this area. Dr. Arjun Gupta: Thank you for this platform. Dr. John Sweetenham: Thank you to our listeners for your time today. If you're enjoying the content on the ASCO Daily News podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclosures: Dr. John Sweetenham: Consulting or Advisory Role: EMA Wellness Dr. Arjun Gupta: None disclosed.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO the mention of any product or service organization activity or therapy should not be construed as an ASCO endorsement.

Host Dr. John Sweetenham, associate director for Clinical Affairs at UT Southwestern Harold C. Simmons Comprehensive Center, and Dr. Robert Carlson, CEO of the National Comprehensive Cancer Network (NCCN), discuss novel therapies and compelling health equity research featured at the 2022 NCCN Annual Conference.   Transcript:   Dr. John Sweetenham: Hello, I'm John Sweetenham, the associate director for Clinical Affairs at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center, and host of the ASCO Daily News podcast.   Today, I'll be speaking with Dr. Robert Carlson, the chief executive officer of the National Comprehensive Cancer Network or NCCN. Dr. Carlson will be telling us about key advances in cancer care that were featured at the 2022 NCCN Annual Conference.   Our full disclosures are available in the show notes and disclosures of all guests on the podcast can be found on our transcripts at asco.org/podcasts.   Bob, I'm really pleased to have you on the podcast today, and personally very excited to serve in my new role as chair of the NCCN Board of Directors.   Dr. Robert Carlson: John, it's a pleasure to be with you this morning and all of us at NCCN look forward to working with you as chair of the NCCN Board of Directors.   Dr. John Sweetenham: Thank you! Bob, there was such a wide breadth of topics that were covered at the NCCN Annual Conference this year. Could you tell us about some of the key abstracts that you think will advance care for patients?   Dr. Robert Carlson: I'd be happy to! We had over 1,000 participants from 40 countries at this year's Annual Meeting. And there were a number of high-quality abstracts reporting on a spectrum of studies, including NCCN young investigators and a number of other investigators.   Three abstracts that I would like to single out include an abstract entitled, “Real-World Data and Independent Predictors of Clinical Outcomes with CDK Inhibitors in Metastatic Estrogen receptor-positive Breast Cancer Patients” which was presented by Priyanka Reddy and colleagues from Case Western Reserve. They assessed how the real-world experience with the CDK 4/6 inhibitors in hormone receptor-positive metastatic breast cancer compared with a clinical trial experience. They retrospectively identified 269 patients with hormone receptor-positive metastatic breast cancer in the first-line setting and assessed progression-free survival and overall survival in the cohort overall, and also in the subset with bone-only metastatic disease in those who had liver involvement.   In the overall cohort, the results demonstrated progression-free survival of 21 and a half months and overall survival of 57.6 months. In those with the bone-only disease, at 5 years, 84% of patients were alive compared with 42% in those with bone plus other visceral sites of disease.   They performed multivariate cox regression, and bone-only disease was an independent predictor of a favorable outcome with a hazard rate of 0.48 for progression-free survival, and 0.38 for overall survival, both highly statistically significant.   In those patients with liver disease, multivariable regression predicted an unfavorable outcome with a hazard ratio of 2.53 for progression-free survival and 2.24 for overall survival. So, the study found that the real-world experience with the CDK 4/6 inhibitors is very similar to that in clinical trials. And that bone-only disease continues to be a positive predictor of outcome and liver disease an unfavorable predictor of outcome.   Another important abstract was entitled, “Reuterin in the Healthy Gut Microbiome Suppresses Colorectal Cancer Growth through Altered Redox Balance,” and was presented by Joshua Goyert and colleagues from the University of Michigan.   This abstract reported on a series of findings related to alterations in the intestinal microbiome, especially related to reuterin, the metabolite from the lactobacillus reuteri.   The investigators found that the fecal metabolites from healthy subjects and wild-type mice suppress colorectal cancer, while metabolites from patients or mice with colorectal cancer do not.   Reuterin was found to be the most potent metabolite in suppressing colorectal cancer. And further study found that Reuterin was effective in inhibiting proliferation and inducing cell death of colorectal cancer, but also in cell lines of lymphoma, ovarian cancer, melanoma, and pancreatic cancer. Normal cells were not found to be at all affected. While early, this all suggests a novel strategy for treatment for translational investigation.   The final abstract to be highlighted was actually funded by the NCCN Oncology Research Program and is entitled “Phase 2 Trial Trifluridine/Tipiracil in Combination with Irinotecan in Advanced Biliary Cancers” and was presented by Sri Tella and colleagues from the Mayo Clinic Comprehensive Cancer Center.   Historically, biliary cancers have had very few and limited treatment options. This current study was an open-label phase two clinical trial in patients with biliary cancer and at least one prior systemic therapy to assess the activity of combination trifluridine/tipiracil plus Irinotecan. The subjects were treated with a regimen of trifluridine/tipiracil 25 milligrams per meter squared, orally, on days 1 through 5 on 14-day cycles, and Irinotecan, 180 milligrams per meter squared intravenously on day one of the 14-day cycles. The primary endpoint for success was 16-week progression-free survival. They enrolled 28 patients 27 of whom were available. And they found a 16-week progression-free survival of 37%, which exceeded their target rate of response of 30% or greater.   Overall survival was just over 1 year. While tolerated reasonably well, those reductions were common, and the investigators concluded that further evaluation in a randomized trial was needed.   Dr. John Sweetenham: Thanks, Bob. All very interesting abstracts. I think that makes important contributions. And in the spirit of interesting discussions at the NCCN, I must say that I personally felt that there were some very interesting and excellent sessions around health equity at the conference, including the plenary sessions.   I wonder if you could give us some key takeaways from those sessions looking at health equity, and also the one that specifically looked at access to cancer care, and equity in the context of access.   Dr. Robert Carlson: So, there were a number of sessions at the NCCN Annual Conference that related directly or indirectly to issues of access and equity of cancer care. I'd like to focus specifically on a plenary session that was devoted to equity in cancer care.   We all know that equities in cancer care are pervasive, and we can't just wish or decree away these disparities. We need to be willing to evaluate how each of us can change our own practice and how we can be an active part of larger systems change. And that is what this plenary session was all about—actively eliminating existing disparities in cancer care.   The session was moderated by Dr. Carmen E. Guerra of the University of Pennsylvania. It started with Thomas Farrington of the Prostate Health Education Network discussing the importance of cancer early detection and screening strategies that are designed to account for the differences in incidence and age distribution of cancers in different racial and ethnic groups.   Mr. Farrington used prostate cancer as an example of where Blacks have an especially high incidence, younger age distribution, and more aggressive prostate cancer than do other racial groups.   Liz Margolies of the National LGBT Cancer Network followed and stated that cancer doesn't discriminate, but the health care system certainly does. She talked about making welcoming spaces for sexual and gender minorities in cancer care settings, of truly learning and understanding the perspectives and needs of the LGBT communities, and gaining their trust. She concluded by saying that being well-intentioned is not enough—hard work is necessary.   Shonta Chambers of the Patient Advocate foundation described the importance of social determinants of health that included socioeconomic factors, physical environment, health behaviors, and health care access and quality. She emphasized the central importance of patient navigation in assuring appropriate access. She described using data and the social vulnerability index to target resources where they are needed the most.   Dr. Maria Garcia-Jimenez from UCLA outlined efforts to improve appropriate racial and ethnic representation across clinical trials, specifically by breaking down barriers to patient participation. Dr. Garcia-Jimenez described how these barriers exist at the health system level, with the provider, at the community level, which typically is through lack of trust, and at the patient level, through lack of trust, language, cultural differences, and lack of awareness.   Alyssa Schatz from the NCCN discussed the Elevating Cancer Equity initiative, which is a collaboration of NCCN, the American Cancer Society Cancer Action Network, and the National Minority Quality Forum, involving a number of additional representatives with expertise in disparities in cancer care. This initiative has developed a health equity report card, which includes 17 measures across 4 different domains, and that has been piloted currently at 5 NCCN member institutions to identify areas of racial access and equity needing improvement. The initiative also developed a series of policy priorities, primarily at the federal level that aimed at minimizing disparities.   The summary of this session is that talking about disparities is inadequate. It is crucial that we take positive and focused action to address existing disparities so that we can improve and facilitate equitable care for all patients. And that equity is everyone's responsibility.   Dr. John Sweetenham: That's great. Thanks, Bob. Yeah, there were 2 statements from that session, which really sort of struck home with me. I think, to your final point there, I know that one of the comments that were made was, 'It is great that there has been so much research in recent years, and so much emphasis in the literature on cancer care disparities. But doing research that demonstrates disparities doesn't actually help the patient. It's what we do about that, which is important. And it's sort of a statement of the obvious, but it's very impactful to me to think about that it's become an area of really quite extensive research, but we actually need some actionable conclusions from those research and to work really hard on that.   The other thing that was said that really struck home with me was the comment that “Cancer is a disease of the family.”' And certainly, the person who said that wasn't talking in the inherited sense, but really more of the impacts that cancer has on the family and the caregivers as a whole.   I thought they were both really impactful statements from what was a really excellent session. Bob, I really appreciate you sharing your insights with us today. Are there any other important messages you'd like to get across before we wrap up?   Dr. Robert Carlson: Well, the Annual Conference of the NCCN serves as a forum to discuss important and rapidly evolving NCCN clinical practice guidelines, to discuss best practices in administering cancer care, and to share the results of a wide range of research activities that relate to improving cancer care. We at NCCN invite the oncology community to next year's NCCN Annual Conference and review the endured materials that will be available sometime this June, from the conference that will be posted on the NCCN website.   Dr. John Sweetenham: Great, thank you! Thanks once again for spending time with us on the podcast today, and for the many contributions that NCCN has made, both nationally and globally, and indeed continues to make to advance quality, effective, equitable, and accessible care for all patients with cancer.   Dr. Robert Carlson: And thank you, John, we look forward to working with you as the chair of the NCCN Board of Directors to further extend all these efforts.   Dr. John Sweetenham: Thanks! Thanks also to our listeners for your time today. If you are enjoying the content on the ASCO Daily News podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclosures: Dr. John Sweetenham: Consulting or Advisory Role: EMA Wellness   Dr. Robert Carlson: Employment (immediate family member): Flatiron Health Patents, Royalties, Other Intellectual Property: Patents relating to inventions as an employee of NCCN Other Relationship: National Comprehensive Cancer Network   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product or service organization activity or therapy should not be construed as an ASCO endorsement.    

Host Dr. John Sweetenham, of the UT Southwestern Harold C. Simmons Comprehensive Cancer Center, interviews Professor Piotr Rutkowski, of the Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Poland, about plans to provide cancer care for Ukrainians fleeing the war in Ukraine.   Transcript Dr. John Sweetenham: Hello, I'm John Sweetenham, the associate director for Clinical Affairs at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center, and host of the ASCO Daily News Podcast. As many of you all know, 2 million people have now fled the war in Ukraine, according to the United Nations Refugee Agency—the UNHCR. Today, we'll be discussing efforts underway in neighboring Poland to provide health care and other support to Ukrainian refugees, particularly for patients with cancer. It's an honor to welcome Professor Piotr Rutkowski, who leads the department of Soft Tissue and Bone Cancer at the Maria Skłodowska-Curie National Research Institute of Oncology in Warsaw, Poland. He also serves there as the deputy director of the Institution for National Oncological Strategy and Clinical Trials. Additionally, Professor Rutkowski serves as the President-elect of the Polish Oncological Society. My guest and I have no conflicts relating to our topic today. Our full disclosures are available in the show notes, and disclosures relating to all guests on the podcast can be found on our transcripts at asco.org/podcast. Dr. John Sweetenham: Professor Rutkowski, thank you for coming on the podcast today. We are really pleased to have this opportunity to speak with you during what must be an incredibly difficult time. Dr. Piotr Rutkowski: Thank you for the invitation. That's true, with this horrible time. And to be honest, we haven't expected how it can be going on. But now we have a new reality, and we have to fight on. Dr. John Sweetenham: Just beginning with that new reality, my first question to you was going to be to ask you a little bit about details of the decisions made by Poland's parliament. So, your parliament has adopted new legislation that provides health care for Ukrainian refugees and enables the creation of a call center at Poland's National Health Fund. Could you give us some more details about these new developments, and how you anticipate this will help the Ukrainian refugees who are suffering, particularly those who are suffering with cancer? Dr. Piotr Rutkowski: Yes, that's true. Until now, we have nearly 1 and a half million people from Ukraine who arrived in Poland during the last 2 weeks. And because of the increasing numbers of patients with cancer coming to our institution but also all the oncology call centers in Poland, the Polish parliament—together with the Polish National Health Fund decided that all refugees of war from Ukraine are authorized to receive health care the same as citizens of Poland. This is very important because it resolves a lot of bureaucratic issues. We do not need to get specific permission to treat the patients. And we can provide them the same care as every citizen of Poland, in terms of outpatient treatment, admission to the hospitals, surgical procedures, access to the drug, prescriptions of the drug . . . it is absolutely important. It also means that within the framework of this new law, we can treat the patients according to all the same regulations, or the same standards, as Polish oncological patients. Of course, I have to stress it, but Ukrainian oncological patients—except, of course—have no priorities. They are going to the same queue and [are under] the same care as Polish patients. Moreover, this is very important because for newly diagnosed oncological patients in Poland—we have so-called oncological cards, which allow for faster diagnosis including pathological evaluation, molecular evaluation, and imaging. So, they are undergoing the same diagnostic procedures as Polish patients. Of course, last week, we have admitted around 100 children in need of oncological treatment to centers in Poland. But probably it was the first wave of patients. Now we have an increasing number of normal adult patients with lung cancer, breast cancer, [and] GI cancers, coming to us. Some of them also need the continuation of the treatment, or they have to start specific treatment with innovative drugs—if they are reimbursed in Poland—it's also allowed to treat with all these medicines in Poland. So, the second point which you mentioned that the Polish National Health Fund established this special, general, official hotline for oncological patients from Ukraine—and also a webpage. This hotline is in Ukrainian, Russian, English, and Polish languages, and with the use of this hotline, we are trying to direct the patients to the proper oncological centers because this hotline from the National Health Fund cooperates with 20 top Polish comprehensive cancer centers. So, using this official hotline, it's much easier to be directed to the correct hospital treating the given type of cancer. This is very important because [patients can] contact directly to the hotline of the National Health Fund or the hotline of the oncology call centers in the region where the patients are temporarily staying in Poland. So, it's the best we can recommend and this is what has been done until now in our country. Dr. John Sweetenham: It's incredible how quickly the Polish government has moved to help the many Ukrainian patients with cancer and other patients who are coming into the country. The cancer centers in countries such as yours, who are accepting and treating these Ukrainian patients, presumably are going to struggle to have sufficient resources in terms of space, equipment, drugs, and staff to handle the large number of patients from Ukraine who will be showing up at your doors. What resources does Poland have? And what do you need from the international community to be able to help with this very large additional patient load that you'll be seeing? Dr. Piotr Rutkowski: Yes, thank you. This is an excellent point because now, of course, the enthusiasm dominates, and normal human help—we involved everybody. So Polish oncological societies are working together, and we are providing different materials: translation for the patients; we also ask the pharmaceutical companies to provide the Ukrainian language material, which we had in the countries, and also patient advocacy groups are really helpful. And we are sending the required medical resources to Ukraine in some official actions. However, of course, you are right that the Polish oncological system had, even before, this increasing number of patients which we can calculate means that we'll have 10 percent more patients with cancer in this year. So, it's a really huge number. Until now, we also had some limitations in resources. The basic drug reimbursement was at a good level when we compare it to other central-eastern European countries, so we had a relatively good system. We also started, 2 years ago, our new national oncological strategy. However, we also transformed to this 3-level system of comprehensive cancer centers of reference.  So, we are also at the level of some transformational oncological systems. So, it's not the easiest time, especially, but generally, the numbers of nurses and health care providers, including different oncological specialties, are limited in Poland. And when we calculate per number of patients, it's one of the lowest in Europe. Generally, we can expect a shortage of human resources. Of course, we can count that we easily and temporarily facilitate the qualification of Ukrainian medical staff for Poland. And this is also included in this package of new laws. But on the other hand, still, we are facing the problems of communication, even with medical staff. So, it's not so easy. Moreover, when we calculated nowadays this number of patients, it costs about 50 to 70 million Euros per month additionally. So, it changes the priorities in health care in Poland. So, I cannot tell you now, but maybe we can make some calculations in 2 or 3 months. But nowadays, we can still resolve these issues, but what will be in 3 or 4 months, I really don't know, And how delayed will the oncology health care be due to [the] increasing number of patients? So, it is what we can anticipate, and we try to reorganize at the level of different hospitals now. We had some meetings with the Ministry of Health and our National Health Fund. And the normal functioning levels—we cannot see. Things are changing. We have first patients now, but the numbers are increasing every day. So, I cannot definitely say what resources, except human resources, and of course, increasing funding, we need in the near future. We try to collaborate with different organizations. I really appreciate the meeting with ASCO and ECO that took place recently about how to transfer some patients to other oncological centers. However, it's not so easy when we can't transfer the patients somewhere else if the patient started the treatment in 1 given center. So, this is the situation now, and what we expect, but it can be more difficult in a few weeks or months. Dr. John Sweetenham: Yeah, thank you. I'd like to perhaps, pick up on that last point you made about medical information on patients that you're accepting. So as a clinician yourself, how are you handling the issue of prior treatment history, and medical information of patients who are coming into your system? For example, are you able to get access to their pathology reports, their imaging, or their prior treatment reports? And if you don't have access to those, how are you facing the challenges of treating those patients with an incomplete medical history? Dr. Piotr Rutkowski: Of course, we have to translate it. So, we have help in our institution, but it's not common practice everywhere. Some of the patients have translated documents. We do not insist on the certified translations, just the original documents or copies of the documents with translation into Polish, because not all words are even well understood. The problem is that the level of health care in Ukraine is sometimes lower, and pathology reports are not perfect. So even if the pathological report, which we are receiving . . . if it's even available from the patients . . . sometimes we need to redo the biopsy and establish some molecular factors. One patient who was admitted to my department yesterday with sarcoma, we redid the biopsy last week because the report was not complete. And we completely changed the diagnosis in 3 days. Other patients will probably also need [to be] re-biopsied. Sometimes we are lacking imaging . . . but some of the patients arrive with at least CDs of CTs or MRIs, so it's much easier. Some of the refugees have only the copy in their mobile phone . . . so the documents are at a very different stage. If we have information about how the patient was treated in Ukraine, it's perfect because they can continue the treatment. But not all kinds of treatment in Ukraine were provided according to the standards which we have in Poland. So, it's also difficult because we have to discuss with patients how to change their treatment. There are really individual situations. This is what I can say. We have a lot of volunteers now helping with translation. We also employed some additional staff and it's easier. But the problems with the documentation probably will also be increasing, that's true. However, we try to simplify as much as possible, and in some situations, redo the biopsy and re-establish the diagnosis, if we have enough information. It's really resolved case by case. Dr. John Sweetenham: Yes, gotcha. It sounds as if it certainly can add to everybody's workload and degree of stress, unfortunately. Because of the additional tests that some of these patients are now having to face, on top of everything else that they've already confronted over the last couple of weeks. One of the other things which I think will be of interest to our listeners in that regard is whether you're experiencing patients who are coming in, who have been part of a clinical trial? And if so, whether there are any mechanisms in place for that situation, or perhaps, a patient on a relatively early-phase clinical trial, who may have received part of their initial treatment in Ukraine? Dr. Piotr Rutkowski: Probably it is the easiest part because, for the last year, I have treated several Ukrainian patients in a clinical trial where they had access to new drugs. And we had the possibility, at least before the pandemic because the pandemic also complicated the transport or movement of patients.  But before, we had several patients in clinical trials, and many of them have relatives and are accompanied by translators who provided for compliance with the requirements for informed consent and of course, understanding all procedures. But because some companies ask us for [the] possibility to transfer patients from Ukraine to Poland within the clinical trials, so they are providing us the certified translation of the documents and also the informed consent in Ukrainian—at least 2 or 3 companies, because I'm responsible for clinical trials in our institute. So, they contacted us and of course, we agreed. This is much easier because it's professional machinery and they have at least documents in the forms of CRF (case reporting form) so we can get the full history, and how the patient was treated, [and] in the majority of cases also imaging. So, it's much easier because everything is provided, and we also inform the bioethical committee about the situation. But it's probably, also, a little more work in the next few weeks. Dr. John Sweetenham: Yes, well it is good to hear that those patients are able to continue their treatment on trial, thanks to all of the backup support that you've been able to provide. I want to conclude by saying thank you, Professor Rutkowski, for coming on to the podcast today. And for everything that you and your colleagues, your institution, and the Polish people—are doing to support patients with cancer during what are obviously extremely difficult times. Dr. Piotr Rutkowski: Thank you very much. You know, cancer is a matter for all of us, and cancer has no borders, so we have to help each other in these difficult times, that's true. Thank you very much. Dr. John Sweetenham: Thank you to our listeners, for your time today. If you're enjoying the content on the ASCO Daily News Podcast, please take a moment to rate and review us wherever you get your podcasts.    Disclosures: Dr. John Sweetenham: Consulting or Advisory Role: EMA Wellness   Dr. Piotr Rutkowski: Honoraria: Bristol-Myers Squibb, MSD, Novartis, Roche, Pfizer, Pierre Fabre, Sanofi, and Merck Consulting or Advisory Role: Novartis, Blueprint Medicines, Bristol-Myers Squibb, Pierre Fabre, MSD, Amgen Speakers' Bureau: Pfizer, Novartis, Pierre Fabre Research Funding (institution): Novartis, Roche, Bristol-Myers Squibb Travel, Accommodations, Expenses: Orphan Europe, Pierre Fabre   Disclaimer:   The purpose of this podcast is to educate and to inform, this is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Dr. Neeraj Agarwal, ASCO Daily News editor-in-chief, and director of the Genitourinary Cancers Program at the University of Utah's Huntsman Cancer Institute, shares key takeaways from the practice-changing ARASENS trial in mHSPC, featured at the 2022 ASCO Genitourinary Cancers Symposium.   Transcript: ASCO Daily News: Hello, and welcome to the ASCO Daily News podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. Today in our continuing coverage of the 2022 ASCO Genitourinary (GU) Cancer Symposium. Dr. Neeraj Agarwal, the editor in chief of the ASCO Daily News will share key takeaways from the practice-changing ARASENS trial, which showed promising results in metastatic hormone-sensitive prostate cancer. Dr. Agarwal has no conflicts relating to the topic of this episode and his full disclosures are available in this show notes. Disclosures of all guests on the podcast can be found in our transcripts at asco.org/podcasts. Dr. Neeraj Agarwal: Hello and welcome to the ASCO Daily News podcast. I'm Dr. Neeraj Agrawal, the director of the Genitourinary Cancers Program and professor of medicine at the University of Utah Huntsman Cancer Institute. Let's discuss the results of the practice-changing ARASENS trial in patients with metastatic castration-sensitive prostate cancer as presented at the 2022 ASCO GU Symposium. This abstract, Abstract 13, was presented by Dr. Matthew Smith from the Massachusetts General Hospital and Hartford Medical School. ARASENS is a randomized phase 3 trial evaluating the efficacy and safety of darolutamide, a novel hormonal therapy, plus ADT (antiandrogen therapy) plus docetaxel versus placebo plus ADT plus docetaxel in patients with metastatic castration-sensitive prostate cancer. Randomization was stratified by the extent of disease and alkaline phosphatase levels, below versus upper limit of normal or above. It is important to know that this study only included patients that were eligible for ADT and docetaxel chemotherapy, to begin with. The primary endpoint was overall survival with multiple secondary endpoints, including time to CRPC (castration-resistant prostate cancer), time to pain progression, time to first symptomatic skeletal event, and time to start off the next anti-neoplastic therapy, and safety. A total of 1,306 patients were randomly assigned to triplet therapy with darolutamide plus ADT plus docetaxel versus placebo plus ADT plus docetaxel. Baseline characteristics were well balanced between the treatment arms. Analysis of the primary endpoint was pre-specified. After, 533 events had occurred results show the primary endpoint of this study was met with a significant improvement in overall survival and a 32.5% reduction in risk of death for patients on the triplet therapy on for darolutamide plus ADT plus docetaxel versus placebo plus ADT plus docetaxel. It is important to know that the triplet therapy improved overall survival, despite 76% of patients in the control arm having received the next life-prolonging therapy. Subgroup analysis indicates consistent benefit across the 3 specified groups. Secondary endpoints also were favored by the triplet therapy combination over the control arm. While this study offers an additional excellent option for our patients with metastatic cancer-sensitive prostate cancer in older populations, the use of docetaxel may be a significant limitation to this triplet combination. In addition, and importantly, this study did not answer the question of whether adding docetaxel chemotherapy to the ADT plus novel hormonal therapy backbone will also improve survival. With the advent of multiple doublets and triplet combinations in recent years, as we saw in the form of ADT plus enzalutamide ADT plus apalutamide in the recent years, it is very important to find biomarkers that may predict response to these treatment options, which will allow personalization of therapy with that. I would like to conclude this podcast on the ARASENS trial. Thank you very much for your kind attention. ASCO Daily News: You've been listening to Dr. Neeraj Agarwal of the University of Utah's Huntsman Cancer Institute. Thanks for joining us today. If you're enjoying the content on the podcast, please take a moment to rate and review us wherever you get your podcasts. Disclosures: Dr. Neeraj Agarwal: Consulting or Advisory Role: Pfizer, Medivation/Astellas, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Merck, Novartis, lily, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, ORIC Pharmaceuticals, CRISPR therapeutics, and Arvinas Disclaimer: The purpose of this podcast is to educate and to inform this is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Dr. Neeraj Agarwal, ASCO Daily News editor-in-chief, and director of the Genitourinary Cancers Program at the University of Utah's Huntsman Cancer Institute, shares key takeaways from the PROpel and MAGNITUDE trials in mCRPC, featured at the 2022 ASCO Genitourinary Cancers Symposium.   Transcript: ASCO Daily News: Hello and welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. Today, in our continuing coverage of the 2022 ASCO Genitourinary (GU) Cancers Symposium, Dr. Neeraj Agarwal, the editor-in-chief of the ASCO Daily News will highlight promising advances in metastatic castration-resistant prostate cancer. Dr. Agarwal has no conflicts relating to the topic of this episode, and his full disclosures are available in the show notes. Disclosures of all guests on the podcast can be found in our transcripts at asco.org/podcasts.   Dr. Neeraj Agarwal: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, the director of the Genitourinary Cancer Program, and professor of medicine at the University of Utah Huntsman Cancer Institute, and editor in chief of the ASCO Daily News. I'd like to start with the PROpel trial followed by a discussion on the MAGNITUDE trial. So, Abstract 11 was on the results of the PROpel trial and presented by Dr. Fred Saad from the University of Montreal. PROpel is a randomized phase 3 trial, which evaluated the efficacy and safety of olaparib, a PARP inhibitor plus abiraterone versus this placebo plus abiraterone in the first-line metastatic castration-resistant prostate cancer setting. Patients were allowed to have docetaxel chemotherapy is given in a metastatic castration-sensitive prostate cancer setting. Enrollment in the study was independent of the effects in the homologous recombination repair pathway. The primary endpoint was investigator-assessed radiographic progression-free survival (PFS) with multiple secondary endpoints, including overall survival and safety.   Approximately 800 patients were randomly assigned to the novel combination of olaparib plus abiraterone or placebo plus abiraterone. Baseline characteristics were well-balanced between the treatment arms, including homologous recombination repair or HRR mutation status. At the pre-planned interim analysis results show the trial meets its primary endpoint with significant improvement in radiographic PFS for all patients receiving the combination therapy versus control, regardless of the presence of homologous recombination repair gene mutations. Median PFS was 24.8 months versus 16.6 months for patients receiving olaparib plus abiraterone versus placebo plus abiraterone respectively with the hazard ratio of 0.66, and a P < 0.0001. This translates into a 34% reduction in risk of progression or death. Overall survival results are still immature with only 29% [of patients experiencing events] thus far. It is interesting that even patients deemed negative for homologous recombination repair gene mutations showed significant improvement in radiographic PFS when treated with the combination of olaparib plus abiraterone versus placebo plus abiraterone.   Regarding the adverse effects, they were what you would expect from the combination of a PARP inhibitor, such as olaparib and abiraterone. We saw a higher sequence of all great events of anemia, fatigue, and nausea in the combination arm. While anemia was the only grade 3-4 adverse event observed at a significantly high frequency in the combination arm. It is also important [that] we get a better understanding of the molecular mechanism by which patients who are homologous recombination repair mutation-negative are benefiting from the combination treatment as well.   The next trial in this context, or this team, was the MAGNITUDE trial. Abstract 12 was presented by Dr. Kim Chi from British Columbia Cancer Center in Vancouver, Canada. MAGNITUDE is a randomized phase 3 trial evaluating the efficacy and safety of niraparib plus abiraterone plus placebo plus abiraterone in the first-line metastatic castration-resistant prostate cancer setting. The study population was slightly different from what we saw in PROpel trial. Taxane chemotherapy, as well as novel hormonal therapy, was allowed in metastatic castration-sensitive prostate cancer, as well as a prior novel hormonal therapy was allowed in the non-metastatic castration-resistant prostate cancer.   Also, patients were allowed up to 4 months of treatment with abiraterone in the first-line metastatic castrate-resistant prostate cancer. Prospective selection of patients with, and without homologous recombination repair (HRR) gene mutations were required. The primary endpoint was radiographic PFS by central review with multiple secondary endpoints, including overall survival and safety. A pre-specified fertility analysis was planned after enrolling 233 patients who were randomly assigned to niraparib plus abiraterone or placebo plus abiraterone. Evaluation of fertility was based on the composite PFS of PSA or radiographic progression, whichever occurred first. The pre-planned fertility analysis showed no benefit in the biomarker negative cohort. And thus the trial did not pursue further enrollment of those patients who were not positive for homologous recombination repair gene mutations.   Coming to the HRR positive cohort, 423 patients were randomly assigned to either niraparib plus abiraterone or placebo plus abiraterone. At the pre-planned interim analysis primary endpoint was met with a significant improvement in radiographic PFS for BRCA1 and BRCA2 and all patients who are homologous recombination repair mutation-positive, receiving the novel combination of niraparib plus abiraterone. Overall survival results are still immature. It is important to note that in the patients who are HRR positive, approximately 50% were BRCA1 and 2 positive. And these patients clearly derived the most benefit with a combination with an approximate 47% reduced risk of death. And if you look at other patients who are biomarker positive, there was a clear benefit and a significant improvement in median PFS (radiographic progression-free survival) with a hazard ratio of 0.73, which translates to a 27% reduction in the risk of death or progression. With the caveat of subgroup analysis, being underpowered following groups of patients seem to derive less benefit with the combination than the overall cohort with the combination of niraparib plus abiraterone. And these patients included patients who were age 65 or younger, or less than age 65, patients with visceral metastatic disease, patients with prior abiraterone or taxane chemotherapy, [and] patients who had a PSL level below the median, and patients with non-BRCA homologous recombination repair mutations.   In conclusion, the combination of niraparib plus abiraterone shows a significant improvement in the radiographic PFS for patients who are HRR positive in the first-line metastatic CRPC. Based on the available data in the public domain, without any doubt that both PROpel and MAGNITUDE trials established a combination of a PARP inhibitor with abiraterone in the first-line metastatic CRPC setting for patients who are positive for HRR mutation improve radiographic progression-free survival. Even though overall survival data are immature for both trials, I expect both combinations will be approved by the U.S. Food and Drug Administration in the near future and will be available to our patients. Regarding the HRR negative cohort in the PROpel trial, which also seems to derive significant benefit with the combination of abiraterone plus olaparib, I'm looking forward to the data on confirmation of HRR negative status by tissue-based genomic profiling results in the full-length publication which we expect to be published soon. If indeed confirmed by the tissue-based genomic profiling, I see the combination of abiraterone plus olaparib to be a reasonable option in the patients who are HRR negative in the first-line metastatic CRPC setting.   With this, I would like to conclude my discussion on the 2 practice-changing trials presented in the 2022 ASCO GU meeting, which were the PROpel and MAGNITUDE trials. Thank you very much for your kind attention. ASCO Daily News: That was Dr. Neeraj Agarwal of the University of Utah's Huntsman Cancer Institute. Thanks for joining us today. If you're enjoying the content on the podcast, please take a moment to rate and review us wherever you get your podcast.   Disclosures: Dr. Neeraj Agarwal: Consulting or Advisory Role: Pfizer, Medivation/Astellas, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Merck, Novartis, lily, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, ORIC Pharmaceuticals, CRISPR therapeutics, and Arvinas Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  

Guest host, Dr. Neeraj Agarwal, editor-in-chief of ASCO Daily News and director of the Genitourinary Cancers Program at the University of Utah's Huntsman Cancer Institute, and Dr. Jason Efstathiou, chair of the 2022 ASCO Genitourinary Cancers Symposium, discuss key abstracts and innovations in GU oncology featured at #GU22. Dr. Efstathiou is professor at Harvard Medical School and director of the Genitourinary Division in Radiation Oncology at Massachusetts General Hospital.   Transcript Dr. Neeraj Agarwal: Hello, and welcome to the ASCO Daily News Podcast. I am Dr. Neeraj Agarwal, the director of the Genitourinary Program and professor of medicine at the University of Utah Huntsman Cancer Institute and editor in chief of the ASCO Daily News. Today we'll be discussing key advances in GU oncology featured at the 2022 ASCO Genitourinary (GU) Cancers Symposium. I'm delighted to welcome Dr. Jason Efstathiou, who was the chair of this year's GU ASCO meeting. Dr. Efstathiou is the professor at Harvard Medical School and the director of Genitourinary Division in Radiation Oncology and clinical co-director of The Claire and John Bertucci Center for GU Cancers at the Massachusetts General Hospital. Our full disclosures are available in the show notes and the disclosure of all guests on the podcast can be found on our transcript at asco.org/podcast. Jason, thank you for coming on the podcast today.   Dr. Jason Efstathiou: Thank you very much, Neeraj. It's a real pleasure to be with you.   Dr. Neeraj Agarwal: So, Jason, the GU meeting showcased some fantastic advances across the spectrum of GU malignancies, can you please tell us about some of the hot topics that made the headlines this year?   Dr. Jason Efstathiou: Absolutely. This certainly was a dynamic and interactive hybrid ASCO GU meeting for all those attending in person, live streaming, or accessing the content on demand. With over 5,200 registrants this year, that's an actual record for this meeting and over 70 countries represented. This meeting truly serves as the premier global event for all those who diagnose, treat and study GU cancers. The meeting highlighted novel scientific and clinical findings that were high impacted. [And] in many cases will lead to practice changing care. The meeting had a real focus on diversity, global perspectives, enhanced interactivity, networking, multidisciplinary, collaborative, and evidence-based care. As you know, this year's theme was “World Class Science, Patient-Centered Care,” and this theme was highlighted throughout the program. The meeting kicked off with a rich day focusing on prostate cancer, lots on PSMA imaging, such as Abstract 9 and a very, very excellent session on PSMA targeting and beyond which explored opportunities and challenges with PSMA novel therapeutics, including biomarkers of response and mechanisms of resistance.   Then Abstract 10 looked at PSMA PET and FDG PET as predictors of response and prognosis in a randomized phase 2 trial of Lutetium PSMA (177Lu-PSMA-617) vs cabazitaxel and metastatic castration-resistant prostate cancer (CRPC) progressing after docetaxel. And it suggested that Lutetium PSMA be prioritized in men with high PSMA expression. And this could actually be predictive. We had some awesome abstracts. Abstracts 222 and 223 suggested that a nozzle digital pathology-based biomarker developed using artificial intelligence is more effective than clinical prognostic markers for predicting long term outcomes in patients with prostate cancer. And that this AI tool can actually successfully guide the use of androgen deprivation therapy in men with intermediate risk localized prostate cancer. And then of course, there were some very exciting results in discussion with the primary results of 3 potentially practice-changing phase 3 trials in the setting of metastatic prostate cancer that were presented in the oral prostate session. These were: PROpel (Abstract 11), MAGNITUDE (Abstract 12), and the ARASENS trials (Abstract 13). Neeraj, as a practicing medical oncologist, what did you think of these 3 abstracts?   Dr. Neeraj Agarwal: I agree with you, Jason. These are indeed practice-impacting, practice-changing abstracts, which was a record for a prostate oral session, all 3 abstracts. In fact, the results of the phase 3 trials are [likely] going to influence or impact our practice in coming months. I would like to start with Abstract 11 on the results of the PROpel trial. So, PROpel is a randomized phase 3 trial evaluating the efficacy and safety of olaparib plus abiraterone vs placebo plus abiraterone. In the first-line metastatic cast of resistant cluster cancer, docetaxel therapy was allowed for these patients if given in the metastatic castration sensitive prostate cancer setting. Enrollment in the study was independent of the defects in the homologous recombination repair gene pathway. The primary endpoint was investigator assessed radiographic progression-free survival with multiple secondary endpoints, including overall survival and safety. A total of 796 patients were randomly assigned to olaparib plus abiraterone or placebo plus abiraterone at the pre-plant interim analysis.   Results show that with a significant improvement in the radiographic progression-fee survival for all patients receiving the combination therapy, regardless of the presence of homologous recombination repair gene mutations. Overall survival analysis is still immature with only 29% event having occurred thus far. It is interesting that even patients deemed a negative for homologous recombination repair gene mutations showed significant improvement in video graphic progression-free survival when treated with the combination of olaparib plus abiraterone versus placebo plus abiraterone. I would like to mention the MAGNITUDE trial, which is Abstract 12, in the same context, as these have very similar populations and combination regimens.   So, MAGNITUDE is a randomized phase 3 trial evaluating the efficacy and safety of niraparib plus abiraterone vs placebo plus abiraterone in the first-line metastatic castrate resistant prostate cancer setting. The eligible patient population was slightly different from that in the PROpel trial—prior attacks in therapy or novel hormonal therapy in the metastatic castration sensitive prostate cancer or non-metastatic castrate resistant prostate cancer were allowed. Also, patients were eligible if they had received up to 4 months of abiraterone in the first-line metastatic CRPC setting. Prospective selection of the patients with, and without homologous recombination repair gene mutations was required.   So, the primary endpoint was radiographic progression-free survival by central with multiple secondary endpoints, including overall survival and safety. A pre-specified early fragility analysis was planned after enrolling 200 patients who are [homologous recombination repair] (HRR) negative and who were randomly assigned to receive either niraparib plus abiraterone or placebo plus abiraterone. The pre-planned fertility analysis showed no benefit in the biomarker negative cohort. Four hundred and twenty-three patients who were HRR positive were randomly assigned to receive either the combination of niraparib plus abiraterone or placebo plus niraparib at the pre-planned interim analysis. The results show that trial method—primary endpoint with a significant improvement in the radiographic progression-free survival for BRCA1 and 2 patients—and all patients who are homologous recombination repair mutation positive [were] receiving the combination of niraparib plus abiraterone versus placebo plus niraparib. Overall survival reserve is still immature.   My combined take on the PROpel and the MAGNITUDE trial, based on the data presented so far or available in the public domain so far, is that both trials establish that combination of a PARP inhibitor plus abiraterone on in the first-line settings for me, for [patients with] HRR mutation positive metastatic castration resistant prostate cancer [will] improve radiographic progression-free survival. Even though overall survival data immature for both trials, I expect both combinations will be approved by the U.S. Food and Drug Administration in the near future and will be available to our patients. The HRR negative in the PROpel trial also seemed to benefit with the combination of abiraterone plus olaparib.   I'm looking forward to data on confirmation of HRR negative status by tissue-based genomic profiling results in the full-length publication, which we expect to be published soon. If indeed confirmed, I see the combination of abiraterone plus olaparib to be reasonable option for patients who are HRR negative in the first metastatic castration prostate cancer set. The last practice changing abstract in the oral prostate session was Abstract 13 on the results of the ARASENS trial. ARASENS is a randomized phase 3 trial evaluating the efficacy and safety of darolutamide plus ADT or androgen deprivation therapy plus docetaxel versus placebo plus ADT plus docetaxel in patients with metastatic castration sensitive prostate cancer or mCSPC.   It is important to note that this study only included patients that were eligible for ADT plus docetaxel chemotherapy. The primary endpoint was overall survival with multiple secondary endpoints, including time to casted resistance, time to pain progression, time to first symptomatic skeletal event, and time to start of next antineoplastic therapy and of course, safety. A total of 1,300 patients were randomly assigned to the darolutamide plus ADT plus docetaxel vs placebo plus ADT plus docetaxel.   Results show the primary endpoint of the study was met with a significant improvement in overall survival and a 32% reduction in risk of death for patients on the triplet therapy with thalidomide plus ADT plus docetaxel. While this study offers an additional excellent option for our patients with metastatic castration sensitive prostate cancer, in an older patient population [the] use of docetaxel may be a significant limitation to this combination. In addition, this study did not answer the question [of] if adding docetaxel to ADT plus a novel hormonal therapy backbone will also improve survival with the advent of multiple doublets and triplet combinations. In the recent years, it is very important to find biomarkers which may predict response to these treatments and personalized therapy.   Dr. Jason Efstathiou: Well, Neeraj, it certainly is a mic drop moment. Isn't it? When you can announce that the New England Journal of Medicine has just released the publication of your ARASENS trial, as you're presenting it at ASCO GU don't you think (DOI: 10.1056/NEJMoa2119115)?   Dr. Neeraj Agarwal: Indeed, I think this is one of the most exciting ASCO GU meetings I've seen ever from GU ASCO. This is not an exaggeration.   Dr. Jason Efstathiou: I totally agree. It was a phenomenal meeting and a very dynamic rich prostate day.   Dr. Neeraj Agarwal: So, let's move on to the bladder cancer. Jason, what are your key takeaways from the studies of bladder cancer presented in this meet?   Dr. Jason Efstathiou: Thanks, Neeraj. Yeah, the sessions on urothelial cancer were phenomenal and there were great sessions on novel therapies, such as antibody drug conjugates in advanced urothelial cancer and management of toxicities. There were abstracts such as [Abstract] 440 suggesting that neoadjuvant gemcitabine and cisplatin produced a favorable pathologic response rate and was well tolerated in patients with high grade upper tract urothelial carcinoma, and thus should be potentially deemed a new standard. Abstract 442 was a phase 2 trial that suggested that maintenance treatment with niraparib plus best supportive care did not improve outcomes compared to best supportive care alone, in patients with advanced urothelial carcinoma that did not progress after first-line chemotherapy.   There was Abstract 435, which was an earlier face study suggesting that neoadjuvant treatment with enfortumab demonstrated promising activity among patients who are cisplatin ineligible with muscle invasive bladder cancer. And then there was a lot of focus in the meeting on trimodality therapy and optimizing bladder preservation. Dr. Alexandre R. Zlotta presented Abstract 433, which was a large multi-institutional match comparison of radical cystectomy to trimodality therapy for patients with muscle-invasive bladder cancer. And it suggested equivalent oncologic outcomes for select patients, and that trimodality therapy should be offered as an effective alternative for these patients. So Neeraj, moving on to kidney cancer, what were your key takeaways from these studies on kidney cancer presented in this meeting?   Dr. Neeraj Agarwal: Yes, Jason, thank you. There were exciting results presented from multiple studies in kidney cancer as well. For example, Abstract 290 presented by Dr. Toni K. Choueiri from the Dana-Farber Cancer Institute on the 30-month follow-up of the KEYNOTE-564, which showed continued and strong disease-free survival benefit with adjuvant pembrolizumab in the context of localized or completely dissected renal cell carcinoma. I would like to highlight that highest benefit was seen in those patients who had oligometastatic disease, who on different surgery to remove those metastatic foresight and then were randomly assigned to receive pembrolizumab vs placebo in this trial. Abstract 291, presented by Dr. Matthew Zibelman from Fox Chase Cancer Center, showed the combination of axitinib with nivolumab was associated with close to 70% objective responses. Abstract 300 on kidney cancer on more than 1,000 patients—and on the International Metastatic Renal Cell Carcinoma Consortium, or IMDC Consortium—show that in the context of first-line immunotherapy regimens, presence of lung metastasis, CT nephrectomy and better MDC risk scores correlated with improved objective responses on this novel immunotherapy regimens.   Abstract 350 on the update of the cabozantinib nivolumab was a sunitinib trial in metastatic renal cell carcinoma in the first-line setting. And it showed that the combination of cabozantinib nivolumab continues to be associated with an improved survival with the 30% reduction risk of death, even after this longer follow up—approximately 3 years. So, indeed, multiple abstracts on kidney cancer with real impact on how we practice medicine. So, Jason, let me switch gears here and talk about the education session. For example, there was a compelling keynote addressed by Dr. Karen Knudsen, the CEO of the American Cancer Society, about disparities in GU cancers in the United States. Are there any key messages that you would like to highlight briefly before we wrap up the podcast today?   Dr. Jason Efstathiou: Thanks, Neeraj. Absolutely. The educational sessions were phenomenal. There was a must-see session, by the way, on management of rare variants in GU cancers. They made management of nuanced, rare variants and rare situations, very practical. And then there was an exciting prostate focus session called “Regulating the Wild West: PET-Based Imaging in Trials and the Clinic.” This session was planned with representatives from the U.S. Food and Drug Administration as we have done for the past 3 years. But this year it looked at how often PET based imaging affects clinical decision making and prostate cancer and how the integration of novel molecular based imaging like PET informs clinical trial design and endpoints, including regulatory considerations. And yes, of course, as you noted this year's program also focused on identifying and addressing disparities in cancer care and research with sessions each day, focused on this topic (Abstract 225, 446, 472, and 26). There were great oral presentations and there was a phenomenal Virtual Poster Walk with Dr. Ahmedin Jemal from the American Cancer Society. He, by the way, is an author that we have all quoted. So, please check that out. But we were thrilled, absolutely thrilled to have Dr. Karen Knudsen, the CEO of the American Cancer Society (ACS) as our keynote speaker to address this important topic in her phenomenal and frankly, inspiring talk called “A Path Forward: Addressing Disparities in Genitourinary Cancers.” This talk was especially poignant because as you know, there is a new and robust collaboration between ASCO and the ACS that was announced earlier this month on February 1, regarding equity, diversity, and inclusion in cancer care. ASCO's work aims to address all of the important differences that can impact access to cancer care and outcomes, including age, gender, race, sexual orientation, and geography, both in the U.S. and internationally. ASCO has clearly aligned its equity, diversity, and inclusion (EDI) goals within the mission pillars of research, education, and quality.   Dr. Neeraj Agarwal: Thank you, Jason, for sharing your insights with us today. It is really an exciting time in GU oncology. Thank you.   Dr. Jason Efstathiou: Thank You, Neeraj. I totally agree.   Dr. Neeraj Agarwal: And thank you to our listeners for joining us today. You will find links to the abstracts discussed today on the transcript of this episode. Finally, if you like what you're hearing on the ASCO Daily News podcast, please take a moment to rate, review and subscribe wherever you get your podcast. Thank you so much.   Disclosures: Dr. Neeraj Agarwal: Consulting or Advisory Role: Pfizer, Medivation/Astellas, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Merck, Novartis, lily, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, ORIC Pharmaceuticals, crispr therapeutics, and Arvinas   Dr. Jason Efstathiou: Consulting or Advisory Role: Blue Earth Diagnostics, AstraZeneca, Boston Scientific, Roivant Pharma, Merck, and Myovant Sciences   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  

Guest host, Dr. Muhammad Shaalan Beg, director for Gastrointestinal Medical Oncology at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center and Dr. Manisha Palta, radiation oncologist at the Duke University Health System in North Carolina and chair of the 2022 ASCO Gastrointestinal Cancers Symposium, discuss key advances in GI oncology featured at #GI22.   Transcript Dr. Shaalan Beg: I'm Shaalan Beg. I'm the director for GI Medical Oncology at UT Southwestern's Simmons Comprehensive Cancer Center. And I'm the guest host for the ASCO Daily News podcast. Today we'll be discussing key advances in GI oncology featured at the 2022 ASCO Gastrointestinal (GI) Cancers Symposium. And I'm delighted to welcome Dr. Manisha Palta, the chair of this year's GI meeting. Dr. Palta is an associate professor and radiation oncologist at Duke University Health in North Carolina. Dr. Palta, thank you for joining the podcast today. Dr. Manisha Palta: Thank you for having me. Dr. Shaalan Beg: Before we begin, I should mention that my guest and I have no conflicts of interest related to our topics today. Our disclosures are available in the show notes and the disclosures for all episodes of the podcast can be found in the show transcripts at www.asco.org/podcast. Manisha, congratulations on bringing together many diverse voices from across the country and internationally to showcase some incredible advances in GI cancer. It's been a big year. I felt that the GI space was falling behind in 2021, and it looks like we've made a lot of progress. Can you tell us about some of the practice changing studies that were featured this year? Dr. Manisha Palta: Yeah, absolutely. So, I definitely think the pandemic slowed things down from a research perspective, but this year we heard some really exciting data. And the sessions that I'd highlight in particular is the hepatobiliary pancreas oral abstracts. So, we heard a number of practice changing studies, one of which is Abstract 379, the HIMALAYA study. This was a phase 3 multi-center study looking at tremelimumab and durvalumab as first-line therapy in unresectable HCC, and was comparing that regimen to the standard of care, sorafenib. In addition to the data for HCC, also presented at this year's meeting in the oral session was Abstract 378, which was the TOPAZ-1 study looking at the systemic therapy regimen of gemcitabine and cisplatin with and without durvalumab as first-line therapy in patients with advanced biliary tract cancers. So, what we're starting to see here is the theme of immunotherapy being incorporated into first-line therapy through these abstracts that were presented. The other particularly interesting abstract in that oral session is a little bit different. Not so much systemic therapy related, but a little bit more focused on the integration of systemic therapy with local regional therapy. And that's Abstract 380, which is lenvatinib combined with TACE as first-line therapy for advanced HCC. And this was a phase 3 multi-center randomized control trial, looking at the incorporation of a local regional therapy with an approved standard systemic therapy as well. So those were the abstracts that I thought were particularly interesting and practice changing in the hepatobiliary pancreas sessions, or the pancreas and hepatobiliary day. However, I also think I would be remiss to not mention another abstract in the first day, the upper GI or esophageal gastric day. Also in the oral session, Abstract 238, which was a randomized control phase 3 trial evaluating 2 chemotherapy regimens and chemotherapy radiation in the neoadjuvant treatment of locally advanced esophagus cancer. And this is the JCOG 1109 NExT study. I think it's a really interesting area, a very exciting area of exactly how we should be managing these patients with localized esophageal gastric cancer. Whether that should be a systemic therapy approach, a chemotherapy radiation approach, or perhaps an integration of both. So those are definitely the key abstracts and practice changing data that were presented at this year's meeting. Dr. Shaalan Beg: Definitely an exciting last couple of years for liver tumors. We saw the approval of atezolizumab and bevacizumab for frontline HCC. There were some concerns about potential toxicities around bleeding and the need for screening endoscopy prior to starting systemic treatments. And one would like to think that the result of the HIMALAYA study, which are looking at combining 2 immune therapy agents together, would have a lower risk of bleeding and maybe a less burdensome way to start systemic treatment for our patients. And gone are the days when we only had one oral kinase inhibitor for our patients. So, very exciting. So, when you think about local regional treatments for GI cancers, a lot of the oral presentations and the key takeaways were around systemic treatment options. When you thinks about supportive treatment options, biomarkers, radiation, surgery, are there any abstracts that come to mind that you feel would be ready for prime time when we return to the clinic next week? Dr. Manisha Palta: So, I think we're starting to see a lot of interesting data emerging with immunotherapy being incorporated earlier into the treatment paradigm. So, what's happened over the last 5 years or so is we're starting to see the use of immunotherapy in the metastatic stage IV setting. And now we're seeing the incorporation and integration of immunotherapy earlier. And so, there's another abstract that was presented in the poster rock session for the esophageal gastric day, looking at the integration of immunotherapy into a chemotherapy radiation backbone for patients who have locally advanced esophagus cancer. And I think we're going to start to see more and more studies incorporating and integrating immunotherapy earlier in the treatment paradigm. So, that would be the thing to look forward to. Is it ready to take to clinic yet? Probably not. But we're on the brink of it I think being incorporated into standard practice. Dr. Shaalan Beg: Yeah, very well said. And talking about early incorporation of immune therapy for GI cancers, there was a study looking at neoadjuvant IPI+NIVO for MSI high gastric cancer, and they found a pathologic complete response rate of 59%. And at first pass we're like, well, MSI high immune therapy, we already knew that. But if you peel that away a little bit, we're talking about path CRs in people who have a biomarker responding to immune therapy. And I wonder if the next question's going to be whether they can be spared surgery for their gastric cancer. Dr. Manisha Palta: Absolutely. Especially when we're talking about surgeries that carry and portend really high rates of morbidity and impair quality of life. Dr. Shaalan Beg: I was interested by a cell-free DNA study from Columbia University, where they reported a very large cohort of GI cancers, think about 30,000 patients cell-free DNA, and found that they're able to identify MSI high microsatellite in stable cancers at a similar proportion as people can identify them with tumor testing. So, remember, these folks with MSI-high disease have very high response rates to immune therapy, like we're seeing in the gastric study. And there was always this concern with cell-free DNA on whether it's as good as tissue testing. And now, this wasn't a paired analysis of tissue and blood in each patient, but overall, they were able to find a similar proportion of MSI-high disease and the different GI cancers. The survival was comparable to what we would expect in that situation. So, I think it's an important next step for cell-free DNA and liquid biomarkers in GI cancer. Dr. Manisha Palta: Absolutely. And I think that just speaks to the theme of the meeting, which is accelerating access to precision care through innovation. So, if we're able to identify these really important biomarkers from blood, rather than having tissue, I think it just allows us to bring these cutting-edge technologies and therapies to patients. And in many cases, therapies that result in significantly less toxicity compared to standard systemic therapies in particular. Dr. Shaalan Beg: Absolutely. One of the highlights of the meeting in my opinion, are the wonderful education sessions and our keynote speakers that addressed health equity, advocacy, and even more in line with ASCO's team for this year. What are the key messages that you'd like to highlight before we wrap up the podcast today? Dr. Manisha Palta: Well, so we had two fantastic keynote speakers this year that were both intended to highlight aspects of the meeting's tagline, accelerating access to precision care through innovation. So, our first speaker, Dr. [K. Robin] Yabroff, spoke about the impact of the COVID-19 pandemic on equity in access to care. I think we often talk about disparities in care, disparities in outcome, but we don't often focus on access. And I think the pandemic has allowed us some opportunities to change how we practice medicine through things like telehealth. And I think these are long lasting effects that will have an impact on cancer care, even after the pandemic becomes less burdensome on our lives. The second keynote speaker was Dr. Theodore Goldstein. He talked about health care technology and how we can use precision care through innovation. What I liked about his talk is that he thinks about cancer and cancer treatment more like a software problem, given his background, and talks about the ways that we can use healthcare innovation to optimize cancer care for patients. So, one thing I'd like to highlight this year was the fact that we had a new educational feature of "episodes" of cancer care. And what we wanted to do this year is we wanted to highlight topics that permeated all of the GI cancers, regardless of site, from upper GI to lower GI. And the first session on Thursday was a series of talks that were focused on the emerging roles of ctDNA on GI cancers. But the second 2 days, Friday and Saturday, were case-based discussions. The first one focusing on broadening access to cancer drugs and the right trials for the right patients. And through case presentations, they talked about how drugs go through the FDA approval process, how sometimes there may be FDA approval and then a change in FDA approval based on additional data, what types of data we may need to actually implement certain new therapies into our standard of care regimens. And then the last session, which was really interesting to me, was the tailoring of systemic and local regional therapies in oligometastatic patients. So, I think this is a really interesting topic. I loved the fact that it was a case-based discussion with multiple panelists from different specialties, talking about the role of local regional therapies in particular, in the treatment of oligometastatic disease. Dr. Shaalan Beg: Definitely a really exciting time in GI oncology. Thank you Dr. Palta for sharing your insight with us today and thank you for your leadership. Dr. Manisha Palta: Thank you very much. Dr. Shaalan Beg: And thank you to our listeners for your time today. You'll find links to the abstracts discussed on this episode in the transcript. And finally, if you'd like to see what we're up to on the ASCO Daily News podcast, please take a moment to rate, review and subscribe whenever you get to your podcast. Thank you very much.   Disclosures: Dr. Shaalan Beg: Consulting or Advisory Role: Ipsen, Array BioPharma, AstraZeneca/MedImmune, Cancer Commons, Legend Biotech, Foundation Medicine Research Funding (institution): Bristol-Myers Squibb, AstraZeneca/MedImmune, Merck Serono, Five Prime Therapeutics, MedImmune, Genentech, Immunesensor, Tolero Pharmaceuticals Dr. Manisha Palta: Employment: Duke University Honoraria: Oakstone Consulting or Advisory Role: Syntactx and VoxelMetrix Research Funding (institution): Merck, Varian Medical Systems, Galera Therapeutics Patents, Royalties, Other Intellectual Property: Up to Date- Annual royalties for being a section author   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Treatment of stroke has changed dramatically in the past decade, with the advent of perfusion imaging and an expanded time window for mechanical thrombectomy. Thrombectomy is now standard of care for eligible patients. But while data clearly supports the use of thrombectomy for certain patients with anterior circulation strokes, the benefit of thrombectomy for patients with basilar artery occlusions remains unproven. Today we'll talk to a vascular neurologist and a neurointerventional surgeon who are trying to better define which patients with basilar artery occlusion may benefit from thrombectomy -- and which patients may not. Series 3, Episode 3   Featuring: - Guests: Dr. Carlo Cereda, vascular neurologist, head of the EOC Comprehensive Stroke Center at the Neurocenter of Southern Switzerland and Faculty of Biomedical Sciences, Università della Svizzera Italiana in Lugano & Dr. Jeremy Heit, Assistant Professor of Radiology and of Neurosurgery and the interim Chief of Neuroradiology at Stanford University - Interviewer/Producer: Dr. Michelle Johansen, Assistant Professor of Neurology, Johns Hopkins Medicine   Disclosures: Dr. Heit disclosed that he consults for Medtronic and MicroVention, and consults and is a member of medical and scientific advisory board for iSchemaView, Inc., and Dr. Cereda disclosed that he is a advisory board for iSchemaView, Inc.

Guest host, Dr. John Sweetenham, associate director for Clinical Affairs at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center and Dr. Syed Abutalib, medical director of the Hematologic Malignancies and Stem Cell Transplant Program at the Cancer Treatment Centers of America in Zion, Illinois, discuss advances in CAR T-cell therapy in the management of lymphoma, the toxicities associated with CAR T, and emerging bispecific antibodies for the treatment of lymphomas.   Transcript Dr. John Sweetenham: Hello, and welcome to the ASCO Daily News podcast. I'm John Sweetenham, the associate director for Clinical Affairs at UT Southwestern Harold C. Simmons Comprehensive Cancer Center and guest host of the podcast. I'm delighted to welcome my friend, Dr. Syed Abutalib, the medical director of the Hematologic Malignancies and Stem Cell Transplant Program at the Cancer Treatment Centers of America in Zion, Illinois. He's also associate professor at the Rosalind Franklin University of Medicine and Science, and founder and co-editor of Advances in Cell and Gene Therapy. Today, we're going to be discussing some of the recent advances in the use of CAR T-cell therapy in the management of lymphoma. Our full disclosures are available in the show notes, and disclosures relating to all episodes of the podcast can be found in our transcripts at asco.org/podcasts. Syed, it's great to have you on the podcast today. Thanks for coming. Dr. Syed Abutalib: Thank you, John. It's my honor. Dr. Sweetenham: Syed, the emergence of CAR T-cell therapy is having a transformed impact on the treatment landscape for hematologic malignancies in general, and for lymphoma in particular, and I'd like to give our listeners a sense of where we're at with CAR T-cell lymphoma. Can you tell us a little about the FDA approved agents which are now being used for the management of patients with malignant lymphoma? Dr. Syed Abutalib:  Sure, so there are, at this time, about five agents that are approved based on mainly a phase 2 single arm study controlling them with the historical data from Scholar One in diffuse large B-cell lymphoma. They are axicabtagene ciloleucel. We'll be calling this axi-cel, which was approved after the data ZUMA-1 for the treatment of adult patients with relapsed/refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy. In this group, there were diffuse large B-cell lymphoma NOS, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and transformed diffuse large B-cell lymphoma from follicular lymphoma. The next agent that was approved was--let's see if I can pronounce it. It's the most difficult name--tisagenlecleucel which is tisa-cel was based on the JULIET trial. This drug was approved again for the adult patients with a relapsed/refractory large B-cell lymphoma after two lines of systemic therapy for the same indications as patients in ZUMA-1 trial except tisa-cel is not approved for the primary mediastinal large B-cell lymphoma. The next agent is lisocabtagene maraleucel. We will call this liso-cel. This agent was approved after the pivotal trial TRANSCEND NHL 001. And the unique thing about this trial was also there were two patients with CNS lymphoma in this trial. And again, the indications were similar to the axi-cel indication. And the fourth indication is for axicaptagene lisoleucel based on the ZUMA-5 trial, which was FDA approved for adult patients with relapsed/refractory follicular lymphoma after two or more lines of systemic therapy. And the last agent that has been approved is based on the trial of ZUMA-2, which is brexucabtagene autoleucel, brexu-cel. And this is approved for adult patients with relapsed or refractory mantle cell lymphoma. Dr. John Sweetenham: Syed, thanks for providing that background. As you've shown, there are multiple agents which have been through early phase clinical trials. They've been applied to various subtypes of malignant lymphoma. And furthermore, they've been used at various stages in the treatment algorithm for these lymphomas, albeit mostly in the relapsed and refractory setting. We've all been waiting for some time to start to see data emerging from prospective randomized trials of CAR T-cell therapy versus standard of care. And of course, we were exposed to some of the early data from these randomized trials at the American Society of Hematology Annual Meeting in December. And overall, there was the suggestion of a possible benefit to CAR T-cell therapy. Could you tell us a little bit about the data that caught your attention and your insights into how to interpret those data? Dr. Syed Abutalib: Yeah, definitely. So as I alluded earlier, right now, the FDA approval is mainly for patients after two lines of therapy in diffuse large B-cell lymphoma. Now what is happening is that this CAR T-cell is trying to move forward into failure after first line of therapy. And in order to do that it is important that they have a comparative arm, which they tried to do in three trials by comparing it with so-called standard of care therapy. However, it must be noted that the standard of care therapy in diffuse large B-cell is not that straightforward for all patients who relapse. So just to give you the background, about 30% to 40% of the patients with diffuse large B-cell lymphoma experience relapse, and 10% are refractory to first line therapy. Now out of these patients, the standard of care therapy applies in real world practice as to the patients who are transplant eligible. For the remaining patients who are transplant ineligible, there is no standard of care therapy. And the list is very long if you look at the NCCN guidelines for those patients. And the patients who are transplant eligible; if 100 patients go to transplant, 50% are cured. And there is a very good track record for this. And the ones who are cured are mainly the ones who are sensitive to chemotherapy, mainly platinum-based chemotherapy. So what these trials that were presented at ASH, one has to understand that what they call standard of care in their comparative arm because what happens is that if you have a comparative arm that is weak, that is not transplant-eligible patients, or the patients don't go to transplant, then your trial would look much better than what it really is. So there were three trials that caught my attention. One is, of course, ZUMA-7, the axi-cel and the second one is the TRANSFORM trial with liso-cel. And the third one is the BELINDA trial, tisa-cel.  ZUMA-7 and BELINDA trial have been published in the New England Journal of Medicine already. So what is important to acknowledge here is that the patients in ZUMA-7 were refractory to frontline therapy. About 74% of those patients were refractory, meaning that they did not respond to [INAUDIBLE]. Now we don't know how bad the refractory disease was, and ideally, these patients, if they are transplant eligible, which most of the patients were, would have gone to auto transplant, and 50% of them historically would be cured and the other patients who are relapsed within 12 months to frontline therapy. Now in ZUMA-7, they assumed that these patients who are early relapse will not respond to standard of care transplant. They divided those patients to CAR-T versus transplant or non-transplant. The reason I say non-transplant, because only 36% of the patients who were on ZUMA-7 received what you call, ‘standard of care therapy,' high dose chemotherapy with transplant. So I don't think it was a fair comparison to standard of care therapy. Now the other thing is the follow up is not too long as it is for the auto transplant. So it remains to be seen how things will evolve. In the TRANSFORM trial, which was with the liso-cel, the large cell lymphoma group were either primary refractory or relapsed within 12 months. Again, they assume that the patients who relapsed early will not respond to platinum-based therapy. Ideally, these patients should go for auto-transplant. In BELINDA trial, what is significant is that only 23% of the patients received auto transplant. And out of the three transplants, BELINDA trial was the only one which did not show improvement in median event-free survival compared to the standard of care. The hazard ratio was 1.01. So it's difficult to say that these trials are truly positive for CAR-T over auto transplant because they did not compare auto transplant in the CAR-T. They compared all patients with relapsed or refractory disease who could have gotten transplant also to CAR-T, favoring the experimental arm. Dr. John Sweetenham: Yeah, thanks Syed. So I think the take-home message that I'm hearing from you is that there are some interesting signals in these randomized studies about the potential efficacy of CAR-T. It's probably a little bit early to claim victory just yet, and we need to let these studies mature out a bit more and I guess ultimately wait for some overall survival endpoints. You're absolutely right that there is still some uncertainty surrounding the interpretation of these results and the long-term effectiveness of CAR T-cell therapy. One thing there's no doubt about is that CAR T-cell therapy is associated with significant toxicities, the most common being Cytokine Release Syndrome and Immune Effector Cell Associated Neurotoxicity Syndrome, or ICANS. But of course, the list of adverse events is much longer. We recognize late toxicities, including prolonged cytopenias. So right now, CAR T-cell therapy is mainly performed at larger tertiary care centers, but obviously, things are changing as regional facilities begin to do CAR T-cell therapies themselves. And even if they don't actually provide CAR T-cell therapy, a lot of physicians are going to be seeing their patients locally after they have developed toxicities from this treatment. How far have we come, do you think, in managing the toxicities of CAR-T, and how can we better manage those adverse events in our patients as we move forward and it becomes a more widespread intervention? Dr. Syed Abutalib: I believe we are getting better in managing these therapies, but of course, the CAR T-cell therapy is at its infancy, and we are learning. In any case, it is important to understand what are the main toxicities-- as you had mentioned, the CRS and the neurotoxicity and the chronic B-cell achalasia or hypogammaglobulinemia, which basically reflects the persistence of CAR T-cell therapy. So, in an effort to improve on recognition and treatment of these side effects, ASTCT, which is the American Society of Transplant and Cellular Therapy, had the workshop in 2018 in Washington DC, and they published a paper subsequently in trying to educate everybody about these toxicities. What is important in CRS is early recognition, and CRS is divided into different grades according to the ASTCT criteria from grade 1 to grade 4. Grade 1 is when you have fever. Many patients that we will admit or who we will treat who are very sick patients will get fever. One should not assume that it is CRS. We should always exclude the infection and start the appropriate antibiotics. And as a transplanter, we are very well-aware of how to tackle this or as treating hematologic malignancies with a lot of neutropenic fevers. So, if you have fever, appropriate workup should be done. Grade 2 ASTCT criteria is fever with hypotension that does not require pressors or hypoxia that requires low-flow nasal-cannula oxygen. Grade 3 is worsening of the hypotension, requiring pressors without vasopressin or hypoxia getting worse. And grade 4 is an extreme with multiple pressures requirement for hypertension and hypoxia requiring CPAP or BiPAP. So all this requires close monitoring and one should also recognize the risk factors prior to the admission of the patient or prior to giving the CAR-T. What are the risk factors for this CRS. The risk factors, which include our high pre-infusion tumor burden, so it is important sometimes to debulk the patient.  Early onset of fever, presence of underlying inflammatory process or presence of infection--these things will help manage the CRS. The other thing is the neurotoxicity. And similarly, there has been criteria developed for that too.  There's an algorithm at our institution, we have developed a card that has this criteria and algorithm imprinted on it. So, there is an ICE criteria which basically checks for patient orientation. And you have certain questions about ability to name three objects, following commands, writing, and attention. You give them certain points. And then you have them go into the neurotoxicity domain and check the level of consciousness and/or their seizures or motor findings or elevated cerebral intracranial pressures. So based on that, you find out what is their neurotoxicity grade. Having said that, it is also important to have toci, which is IL-6 inhibitor, on hand. And according to the regulatory authorities, these drugs are approved under the REMS program. So you have to have at least two doses of tocilizumab in-house before you give any patient these drugs. So, to answer your question in a nutshell now is that close hemodynamic monitoring is very important, and it is important to have trained staff on board who can check on patients at regular, frequent intervals to recognize these toxicities early and intervene early to prevent morbidity and mortality. Dr. John Sweetenham: Yes, thanks. And I think it emphasizes the fact that the initial patient selection for CAR T-cell therapy is extremely important bearing in mind not just the patient's disease state but also age, performance status, co-morbidities, and so on in the same way, really, as with transplant. I want to change gears just for a moment. There is no doubt that cellular immunotherapies like CAR-T remain of limited availability in part because of cost and effectiveness barriers. And without getting into a long discussion about that, I wonder if you could comment a little bit on other emerging therapies that in time could potentially, if it's the right expression, challenge CAR T-cell. I'm thinking in particular about some of the bispecific T-cell engaging antibodies which are now coming online. Dr. Syed Abutalib: Sure. So the bispecific antibodies are basically protein constructs with a specificity to two different antigens. And they commonly bind immune effector cell antigens and tumor-specific antigens, creating what we call an immune synapse, which results in activation of the effector cells, which are T-cells, and cause direct cytotoxic activity. For example, we have an FDA-approved agent in ELL, and it's also listed in NCCN as an-- in transplant-ineligible patients, which is blinatumomab, which is a CD3 and CD19 construct. Now in the clinical trials, there are many bispecific antibodies that are in development. The benefit of this is manifold, in my opinion. They are off-the-shelf immunotherapy. They have strategies to mitigate CRS and neurotoxicities such as that they are given those adjustments with lower rates of doses early on and then the dose is escalated. And we see less CRS and neurotoxicity in patients. The third advantage is they might be preferable, especially in older adults.  I'm not sure if they are going to replace the auto transplant at this time. The other advantage is that there is data emerging that they are effective even after CAR T-cell therapy failures although the data is not mature yet. And still, we need them to be approved and see how they will be in the real world setting. So some of them I will talk about. The one that really caught my attention was mosunetuzumab, which is called mosun. The unique thing about this is that it's IV, and there is a step up dosing to mitigate the CRS and neurotoxicity as I mentioned.  And it is a time limited therapy. It's not that you have to keep going, and that is important because of the cost effectiveness of the therapy. And this is a CD3 and CD20 construct. It is being tested in the third line follicular lymphoma as monotherapy in combination of Revlimid. The important thing is that the CR grade 3 and grade 4, very few patients, 2 patients out of 90 in follicular lymphoma, and no grade 4, grade 5 events occurred whether with monotherapy in follicular lymphoma with a CR rate of about 58%. They are also being combined with polatuzumab, which is an anti-CD79 antibody and also in relapsed/refractory diffuse large B-cell lymphoma as a subcutaneous dose because of, again, further trying to mitigate the CRS with a slow release form. The other important biphasic antibody is glofitamab, which is being tested in relapsed/refractory follicular lymphoma, relapsed/refractory mantle cell lymphoma after BTKI, failures. And also, the data in more than 200 patients was presented in patients with diffuse large B-cell lymphoma, mantle cell lymphoma, transformed follicular lymphoma, Richter syndrome. So these two are very important to watch for. There are others, such as epcoritamab, which is also C3 and CD20 bispecific antibody, which is also in a phase III trial, what is the standard of care in relapsed/refractory diffuse large B-cell lymphoma, and is also being tested upfront with R-CHOP. So I think these three are important to watch out for, and in my opinion, which might be incorrect, these are, as I alluded earlier, are more convenient, less laborious, can be less CRS, and might have about similar-- might have similar activity as CAR-T, might win the game over CAR-T. But it's too early to say. It's just an opinion. Dr. John Sweetenham:  Thanks, Syed. And I think however this plays out, however, ultimately, these bispecific antibodies line up versus CAR T-cell therapy, I think two things are true for sure. The first of those is that patients with aggressive lymphomas and indolent lymphomas now have available to them a number of treatment options they didn't have before, which, of course, is great news. The second thing which is undoubtedly true is at least for a while, CAR-T therapy is with us to stay. Syed, it's been a pleasure having you on the podcast today and hearing your insights into how CAR T-cell therapy is evolving and its potential to improve patient outcomes in the future. Dr. Syed Abutalib: Thank you, John. Dr. John Sweetenham: And thank you to our listeners for your time today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclosures: Dr. John Sweetenham: Consulting or Advisory Role: EMA Wellness   Dr. Syed Abutalib: None Disclosed   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  

Dr. Karim Fizazi, medical oncologist at Gustave Roussy and professor in Oncology at the University of Paris-Saclay in France, tells guest host, Neeraj Agarwal, editor-in-chief of ASCO Daily News and director of the Genitourinary Cancers Programs at the University of Utah's Huntsman Cancer Institute, about the practice-changing PEACE-1 trial, an ongoing phase 3 trial among men diagnosed with de novo metastatic castration-sensitive prostate cancer.   Transcript: Dr. Neeraj Agarwal: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, the director of Genitourinary Oncology Program and professor of medicine at the University of Utah Huntsman Cancer Institute and editor-in-chief of the ASCO Daily News. Our topic today is the practice-changing PEACE-1 trial, an ongoing phase 3 trial among men with de novo metastatic castration-sensitive prostate cancer.   Joining me today to discuss the results of this trial is Dr. Karim Fizazi, who is a world-renowned medical oncologist practicing at Gustave Roussy and a full professor in Oncology at the University of Paris-Saclay in Villejuif, France. Dr. Fizazi has led multiple practice-changing trials in advanced prostate cancer and is also the founder of the Prostate Cancer Consortium in Europe known as PEACE Consortium. Our full disclosures are available in the show notes, and disclosures related to all episodes of the podcast can be found on our transcripts at the asco.org podcasts. Welcome, Karim. It is so great to have you on the podcast today, and thank you so much for taking time to be with us.   Dr. Karim Fizazi: Thank you very much, Neeraj. It's a pleasure and an honor.   Dr. Neeraj Agarwal: You recently presented the primary results of the phase 3 PEACE-1 trial in men with de novo metastatic castration-sensitive prostate cancer in the ESMO 2021 meeting. Could you please tell us more about the design of this study and why you did this study?   Dr. Karim Fizazi: Sure, yes, happy to do so. So, PEACE-1 is a large academic European phase 3 trial, which is enrolling patients with de novo metastatic prostate cancer. And it is basically asking 2 questions. Number 1, should we add abiraterone acetate on top of standard of care for these men? And in most of them, standard of care consisted in androgen prevention therapy plus chemotherapy with docetaxel. So, this is the number 1 question—in other words, 3 drugs instead of just 2.   And the second question is whether we should use radiation therapy directed to the primary cancer in these men who are treated with intensive systemic treatments? And we're doing that because we already know the answer regarding the radiation question, and it's a yes answer for men who received androgen deprivation therapy (ADT) alone, but we don't really know whether this applies when intensified treatment is being used.   So, it's a 2x2 design, and we were able to enroll almost 1,200 men in the trial. We completed the inclusion in the trial back in 2018, so the patients or at least those who are alive are on follow-up. And this year, 2021, we have analyzed the co-primary endpoints of radiographic progression-free survival and overall survival for the abiraterone equation. In probably 1 or 2 years from now, we will be able to do the same thing regarding the radiation therapy equations when we have sufficient number of events for these patients.   Dr. Neeraj Agarwal: Very interesting trial design and massive effort at the multinational level in Europe. So please tell us about the results of the study and how it will affect the current treatment paradigm of our patients with de novo metastatic castration-sensitive prostate cancer.   Dr. Karim Fizazi: Sure. So, as I said, right now, we have data regarding the abiraterone question. And again, the question is whether we should use ADT plus docetaxel with or without abiraterone acetate and prednisone. At ASCO [Annual Meeting] this year, we reported the radiographic progression-free survival data, which is a co-primary endpoint of the trial, and this is clearly positive (Abstract 5000). If patients received 3 agents—ADT, docetaxel, and abiraterone—they will enjoy 4.5 years without radiographic progression or death in the experimental arm versus only 2 years in the control arm. So, in other words, this mean 2 and a half year of additional life without problems, if you will, without a significant progression or death for this patient, which is big.   I think many people were already convinced with this data and thought this could be practice changing. I remember our discussion, you and me, Neeraj, at this time. But some others were not necessarily convinced and request the overall survival data before making their decision. Or if it's possible to collect the events, and of course, in the COVID-19 times, this has been challenging. But I think we made it, and we were able to show the data for overall survival at ESMO this year in September. And of course, this was planned—pre-planned and dependent on a pre-planned number of events, which was reached. The news here is good again. And actually, patients receiving ADT plus docetaxel plus abiraterone clearly have an improvement significantly by overall survival as compared to those who received just 2 treatments. The reduction in the risk of death was approximately 25% for these patients receiving the triplet treatment, and it's even greater for men with what we call high-volume disease, so those with multiple bone metastases, at least 4, or visceral metastases, of course, men with a poor outcome. For these men, the reduction in the risk of death achieved by the triplet treatment was 28% in reduction of risk of death and was translated in a marked difference in medians, 3.5 years in the control arm with ADT plus docetaxel, and this was actually what we were expecting for this population of men, as compared to 5.1 years for patients receiving the triplet treatment. So, in other words, it's more than 1 and a half additional year of life for these men receiving 3 treatments up front.   I think what is very unique also in this trial is that men in the control arm were treated very aggressively when they progressed. And actually, more than 80% of them received at least one next-generation hormonal agents, and basically, 85% of them received at least 1 drug associated with proven life prolongation. Again, this is in marked contrast to what we saw in previous pharma industry-sponsored trial conducted in the past, where patients in the control arm were not necessarily very aggressively treated. This is clearly showing us that—   Dr. Neeraj Agarwal: Yeah. This is very interesting. I was really impressed by the fact that patients in control arm and as well as experimental arm—so basically patient on ADT plus docetaxel versus ADT plus docetaxel plus abiraterone—more than 80% patients were receiving subsequent life prolonging therapies, which is in marked contrast to other trials we have seen in the recent past. And despite that, you were able to show a remarkable, clinically meaningful improvement in overall survival with the triplet therapy. I think that is the most important message I got from the updated presentation in ESMO 2021. Would you agree?   Dr. Karim Fizazi: Absolutely. I think it's truly a demonstration that early intensification is better than use—a subsequent use of these agents when the cancer is already more heterogeneous, more aggressive, and harder to treat. We should intensify treatment up front. I think this is very important, especially those with predicted poor outcome.   Dr. Neeraj Agarwal: So, Karim, these data are obviously very impressive, in my view, practice changing. Many of my community oncology colleagues have asked me about the potential side effects of this combination versus chemotherapy with docetaxel or abiraterone therapy alone in addition to ADT. Any tips for our colleagues and friends out there in the community on how to manage side effects or what should we be looking for as a community? What should we be telling the patients and any tips on managing the side effects?   Dr. Karim Fizazi: Absolutely. I think this is a key question, and also, this was great news from the trial. We couldn't find basically synergistic toxicity between docetaxel and abiraterone in the trial. So, in other words, what we saw was the expected toxicity from docetaxel, and we expected toxicity from abiraterone, but nothing additional or nothing worse, if you will. For example, the neutropenic fever incidence was exactly the same in the two arms. The GI toxicity from docetaxel was not increased, and actually, it was even a bit less, numerically speaking at least.   And regarding the abiraterone toxicity, what we saw mainly was an excess in hypertension, usually of lower grade, and an excess in transaminase increase, which was actually rare, approximately 6% if I recall well, which is really in line with what you would expect with the general use of this agent. And of course, this is something you can monitor, and you should monitor. We know how to handle toxicity with abiraterone, and the same also applies to the hypertension management with this agent.   Dr. Neeraj Agarwal: Got it. So, say a patient is hesitant, and of course, this was not addressed by the clinical trial. But given compelling survival benefit, if I'm talking to a patient in the clinic tomorrow morning and the patient is hesitant to start all 3 drugs at the same time, do you think it would be reasonable to start chemotherapy with docetaxel, finish 4 to 6 cycles, and then start abiraterone? With the caveat that this was not addressed by the trial, but I'm just asking a very practical question.   Dr. Karim Fizazi: Again, this is a difficult question you're asking. And I'm saying that because, as you rightly said, in PEACE-1 we combined abiraterone with docetaxel. So, in other words, abiraterone was given concomitantly with docetaxel and then was continued when docetaxel was stopped. So, we don't really know whether giving abiraterone as a maintenance strategy, if you will, in your example, post docetaxel would be associated with the same benefit. It's probably reasonable to think it does, but it's not a given. So, my preference would be actually to combine up front, if possible, of course.   Dr. Neeraj Agarwal: Absolutely. And as I said, this was not tested or addressed by the trial. So final message is, as far as combination therapy is concerned, there is no synergy—there is synergy with the efficacy, but we are not seeing synergy, if you will, from the side effect perspective. And if we are deciding to start triplet therapy, we should be starting all drugs at the same time. At least docetaxel and abiraterone should be started together and not sequenced. Any final message for our friends and colleagues in the community by you, Karim?   Dr. Karim Fizazi: Well, maybe just 1 or 2 final messages. The 1 is a hurrah message because I'm happy, of course, with the data. And just to put this into perspective, back in 2015, before we had all of the recent trials in M1 castration-sensitive disease, men with high-volume disease had approximately 3 years of life expectancy. And now just 5 or 6 years afterwards, thanks to all clinical research we conducted during this time frame, in PEACE-1, these patients can live more than 5 years, which I think is remarkable.   I think the second and last message is that we should soon have more data for these men regarding the triplet combination with ADT, docetaxel, and a next-generation hormonal agent. Specifically, the ARASENS trial (NCT02799602), which is testing darolutamide randomly in this setting, is to release its data probably very soon. And the same applies to the enzalutamide trial with ENZAMET, which should be updated specifically for these men receiving the triplet treatment. So, we should see even more data than what I was fortunate enough to report this year with PEACE-1.   Dr. Neeraj Agarwal: Thank you. So, thank you, Karim, again, for sharing these exciting data from the PEACE-1 trial. Congratulations for conducting this massive trial and coming out with such great news for our patients. I wish you all the best.   Dr. Karim Fizazi: Thank you very much, Neeraj. It was a pleasure. Thank you so much.   Dr. Neeraj Agarwal: And thank you to our listeners for your time today. If you enjoyed this podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Thank you very much.   Disclosures: Dr. Neeraj Agarwal: Consulting or Advisory Role: Pfizer, Medivation/Astellas, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Exelixis, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Foundation Medicine, Gilead Sciences Research Funding (inst.): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, ORIC Pharmaceuticals, crispr therapeutics, and Arvinas   Dr. Karim Fizazi: Honoraria (inst.): Janssen, Sanofi, Astellas Pharma, Bayer Consulting or Advisory Role (inst.): Janssen Oncology, Astellas Pharma, Sanofi, AstraZeneca, ESSA, Amgen, Bristol-Myers Squibb, Clovis Oncology Consulting or Advisory Role: Curevac, Orion Pharma GmbH, Bayer Travel, Accommodations, Expenses: Janssen, MSD   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  

Guest host, Dr. John Sweetenham, associate director for Clinical Affairs at the UT Southwestern Harold C. Simmons Comprehensive Cancer Center, and Dr. Derek Raghavan, President of the Levine Cancer Center at Atrium Health in North Carolina, discuss some of the major issues ahead for the oncology community in 2022, including tension caused by the COVID-19 pandemic, achieving true equity of care, how to use molecular testing in an optimized fashion, and the future of the oncology workforce. Transcript  Dr. John Sweetenham: Hello, and welcome to ASCO Daily News podcast. I'm John Sweetenham, the associate director for Clinical Affairs at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center and guest host of the podcast. Today, we'll be discussing the challenges ahead for the oncology community in 2022 with Dr. Derek Raghavan, President of the Levine Cancer Institute at Atrium Health in North Carolina. Our full disclosures are available in the show notes, and disclosures relating to all episodes of the podcast can be found on our transcripts at asco.org/podcasts. Derek, always a pleasure to have you here, and great to have you back on the podcast again.   Dr. Derek Raghavan: Hey, John. Always enjoy chatting together.   Dr. John Sweetenham: Derek, we're interested today to get your insights into what you think are going to be the major challenges facing the oncology community in 2022. I think each of us could come up with a pretty substantial list, but very interested to hear what you think are going to be those issues which are going to be uppermost in our mind as we move into the new year.   Dr. Derek Raghavan: Well, I think there are a number of important issues, John. I think everybody in clinical practice, medical or nursing, or whatever, have been brutalized somewhat by the COVID-19 pandemic, and I think everyone's tired and a bit cranky, and they're upset with a schism between the fringe and the science-based clinicians. So, I think that underscores everything. And there's an anxiety and a tension that I think is just new.   From the practical standpoint, which is where I think your question is directed, yeah, I think there will be issues that relate to achieving true equity of care. And I think hopefully, the focus will move from analysis paralysis to actually doing things and measuring outcomes. I think there will be the tension between value, price, and cost. People are spending an awful lot of money on health care. That's going to be an issue.   We have very good information on molecular prognostication, but a lot of the data that are coming out are from technologies that are not fully validated and not even standardized. There's a lot of disinformation and misinformation coming out, and I think we're going to have to address that. I think those are 3 themes that could keep us talking for quite a while.   I think the other thing, which is more up your alley than mine, is we've been watching CAR T[-cell therapy] emerge. I think we've got a beginnings of a pretty good handle on how CAR T[-cell] relates to hematological malignancy. It's much less clear in the solid tumors, and there is a bit of a tendency to do what used to happen in the 1970s and '80s, which is here's a new treatment. Let's give it a whack and see what happens.   But this is very expensive. We don't want to fall into the trap of how bone marrow transplant was introduced as a standard of breast care management for nearly a decade, based on somewhat flimsy evidence. So, we need to be a little more thoughtful about how we introduce CAR T[-cells] into the solid tumors.   Dr. John Sweetenham: Thanks. Yeah, plenty to discuss there, as you say. And what I'd like to do just because it is such a topical issue and continues to be at the moment is just pick up a little on the COVID-19 theme. I think that we've all seen a great deal of discussion in recent months about many of the consequences of COVID-19, including delayed screenings, late diagnosis, clinician burnout, and so on. But I'm interested in your insights on a couple of things.   Number 1, since we're now seeing the emergence of further new variants, what do you think that this is going to mean for the oncology community in terms of handling these new variants within the context of our patients with cancer? And then secondly, because I'm intrigued by one of the things you mentioned in our discussions about this podcast, you mentioned the changed relationship between health professionals and parts of the community as a consequence of COVID-19. And interested to hear you expand just a little bit on that. So, kind of 2 questions wrapped up in 1 there.   Dr. Derek Raghavan: Yeah. Well, I think the 2 are connected. The old style of physicians has always liked to be sure of their ground and to have a firm database when they talk about things. Particularly with the new variants, while it's completely appropriate to be transparent about the fact that they knew that they seemed different and so on, I think there is the problem that there are a lot of physicians who are now becoming TV personalities as much as physicians and who are talking all the time.   I'm not critical of that, but the problem is that they're being honest in saying we don't really know this, but this is what I think, and then they have to change direction. So, what's happening is, for the first time in a long time, physicians are regularly being quoted and being seen as saying things that are not necessarily correct, and that reduces confidence by the community and the physicians. At the same time, COVID-19, in my view, highly, inappropriately became a political football.   You have people who have absolutely no training, so radio hosts, football quarterbacks, basketball stars making extraordinary statements about COVID-19 and their approach to vaccination, masking, and other things where they have absolutely no business doing it. But they are people who are believed. They're high profile. And so, there's now a schism emerging between patients who listen to people who have no medical training at all and no basis for what they say and those particularly in the political domain who have politicized this and created a situation where, once upon a time, a physician was at least seen as coming from the right place and with good intent.   But we've both seen so many of these public demonstrations where physicians and public health physicians are being castigated for simply espousing good practice. Now, with respect to managing the variants, I think the fact is we have some basic principles that I have believed now for 2 years. Masks reduce the chance of getting any type of COVID-19. They just do. If you wear a mask most of the time when you're out and about, you're going to cut your chances down. Vaccination reduces the chance of ending up in the ICU unless you have some sort of immunological deficit.   Dr. John Sweetenham: Yeah. I'm going to switch gears now and return to the first thing that you mentioned right up front, which is the issue of equity and how we are going to address equity issues in the coming year. I think that in many ways, 2020, going into 2021, has been 2 years where issues of equity in health care have really come to the fore. And of course, there's been a great deal of discussion around this.   And I think you'd agree with me that we've seen, at the same time, that some of the strategies that we have been using during the COVID-19 pandemic, including telehealth, which one would have hoped would be a great equalizer, actually has the potential to exacerbate some of the disparities that we've been seeing in health care. But you mentioned analysis paralysis, and just to pick up on that theme, despite the huge amount of coverage that equity has received in medical journals and the media, where do you think we actually are in finally truly addressing some of the cancer care disparities that we see?   Dr. Derek Raghavan: Well, I think, John, you know that I was one of the early chairs of the ASCO Task Force. Otis Brawley and I chaired that task force together. Very early in the piece, I'm going to say probably 15 years ago, we wrote really quite a strong position paper on this whole issue. And so, we got started early in doing stuff on what we thought would be important, and we did, with support from the Komen Foundation, was to start training people of color in the oncology space and keeping them working in underserved communities by paying off their college loans for the period of time that they did that.   So, people have been doing stuff for a while. I think what's happened in the last decade, and it has been a slow change, is that there's been more a move to saying, let's get started. So, if you look at Chris Lathan up at Harvard, at one of their underserved hospitals, if you look around the country, consider the Bristol Myers Squibb Foundation, which puts money into active projects that are about doing stuff rather than having meetings to consider doing stuff. I think there's been that swing.   Dr. John Sweetenham: When we think about equity and disparities of care, we're often drawn towards the cost of cancer care and how much that plays into disparities and inequity in the delivery of cancer care. And picking up on that theme that you mentioned around value, cost and price, and maybe we could think about linking that with the use of CAR T-cell therapy and the application of CAR T-cells in the solid tumor world, if that is going to happen, what do you think we can do during 2022 to confront some of the cost and price issues that we're seeing within our cancer care environment right now?   Dr. Derek Raghavan: Well, I sometimes think in a utopian fashion, which doesn't get me very far, I have to say. What I'd love to see in the United States, because we spend far more money on everything health-wise than any other country in the civilized or uncivilized world, but what I'd like to see is a bipartisan initiative run by people who actually understand health care and health care economics that would go to the issue of, how do you get better bang for your buck? And it would include doing some tough things.   We waste money outrageously. We'll treat third-line metastatic pancreas cancer off trial. Nothing works in third-line metastatic pancreas cancer off trial. It's worth maybe a clinical trial to help the next person in line. That's how we make progress. But just to keep giving the same old litany of drugs in the hope that it might work is a waste of money. As I talked about before, BMT for breast cancer turned out to be a huge waste of money over a long period of time. So, if you can actually create a scenario where government set some rules and took the courageous, and this why it would have to be bipartisan, it would actually start to rationalize health care.   You know, John, the Oregon experiment many years ago, where one party started to rationalize care, and the other party accused them of rationing care. I mean, you can't have that happen. We've also seen both sides allocate the task of developing health care algorithms to people who are great politicians but know nothing about health care or economics. So, I mean, there are easy ways to do it. What we can do ourselves is be honest. Tell people what bang they'll get for their buck.   The person who is likely to have, say, an 80% chance of being dead within 4 months may not wish to mortgage his house if he's told that. On the other hand, he might well want to mortgage his house if he thinks that a very expensive treatment will give him the chance of being alive in 5 years. So, we, as physicians, shouldn't make that decision. It's the patient's right to be able to choose life versus the life of their offspring and spouse and future generations. So, I think it's not that complex, and I think if we brought more transparency about good expectations versus poor expectations, gave a better reason for patients getting more involved in trials, we're still at less than 15% of patients with cancer in the USA getting involved in trials, and that's a tragedy.   Dr. John Sweetenham: Yeah, I think also, the other thing that's occurred to me in this context, is the fact that while we tend to hone in on costs of treatment when we get into these discussions, I've been seeing some emerging literature around the cost of follow-up and unnecessary follow-up and imaging and so on in those patients who are in survivorship part of their cancer journey. And there's a huge opportunity there, I think, for us to reduce costs of care with no impact whatsoever on survival, no difficult treatment decisions to be made because we're simply doing an enormous amount of unnecessary testing in these patients who have completed treatment that we know doesn't impact survival. So, I do think that we could take a really serious look at that and make very significant savings. So, I think there's lots of potential there too.   Dr. Derek Raghavan: Yes. I agree, John. And I'd actually give kudos to ASCO in this space because they were early adopters of the Choosing Wisely campaign. They wrote two sets of guidelines about stupid things that we do that make no difference. And to be honest, I think that--I was on that committee, and the committee got tired.   I was one of the few people that actually felt we should keep going and very actively keep issuing guidelines of things that just aren't worth doing and having symposia at the ASCO ASM say that the symposia that are entitled “How to Waste Money” or alternatively entitled “How to Stop Doing Dumb Stuff” would be really quite important. And it would give the basis for sensible medicine to people who do medical legal protection work. So, most people who do multiple PET scans on lymphoma where the patient is completely well and blah, blah, blah are doing it for medical-legal reasons. They're not doing it because they think it will make a huge difference.   And I, of course, am not talking about the people where they're following PET scans as markers of response. So, I think we can do this work. I'd love to see a presidential campaign which is about not doing dumb stuff and where ASCO takes the bully pulpit and says, “we're spending a year policing ourselves, talking about all the things we do that don't actually make things better for patients.”   Dr. John Sweetenham: So, let's extend this theme of expensive therapies. And you mentioned CAR T-cell therapy. And in the hematologic malignancy world, we're now just beginning to see 1 or 2 results, which will be presented at the American Society of Hematology meeting in a couple of weeks from now, positive results from a couple of randomized clinical trials in hematologic malignancy with CAR T-cell therapy. So, what are your thoughts on the application of this treatment in the solid tumor world, and where do you think we are, what do you think we might see during 2022?   Dr. Derek Raghavan: Well, let's talk strategy first. I think a good place to begin is with a good scientific hypothesis. So, we both know how CAR T[-cells] work. We don't have to have a long discussion here about them. It would be patronizing to the audience. But you might think about, what solid tumor is actually going to benefit from immunological manipulation? Where have the checkpoint inhibitors been helpful, and where have they not been helpful? And so, you might focus the initial part of CAR T[-cells] and solid tumor work on those where there's a hypothesis that makes sense.   Then the second thing you could do would be to actually come to the companies that make all their money from CAR T[-cells] and say, perhaps you could invest in this research with us, and we'll do a couple of Hail Mary passes. So, let's look at the tumors where there isn't a good hypothesis, but nothing works, and see if we can get an experience. So, that'd be a nice, simple, easy way to do it. And then measure tight outcomes, have very robust entry criteria so you don't get confused about various toxicities because you're actually starting with patients in reasonable shape and then expanding to all populations.   So, the first part would be phase 1 and 2. Then you, early in the piece, make sure that you have inclusiveness so that you know all the population groups that might benefit from the treatment. I think that'd be a reasonable way to go.   Dr. John Sweetenham: Talking about identifying targets appropriately and target populations for treatment, you had mentioned as one of your other challenges for 2022 the concept around identifying molecular subgroups and molecular prognostication as a way of patient selection. So, could you say a little bit more about that and what you think we're going to need to do in the coming year in terms of refinement of targets?   Dr. Derek Raghavan: Well, John, this is an area of your expertise as well, coming from the hematological malignancy world. Now, I hope we would both agree that having robust reproducible technology is important. The fact that there are so many molecular diagnostic companies that hype their product doesn't necessarily mean that the product is good. So, there needs to be standardization of approaches to using technology, to measuring outcomes.   We need to have comparative sets of data, looking at different technologies to see how they work, and those sorts of studies need to be funded by government because there's no particular reason for the companies to agree to perhaps show that their diagnostic technology is not as good as somebody else's. But this would be a good initiative for the government to actually start to rank order of the products that are out there. I, frankly, think when you think of the impact of all of these molecular diagnostic tests, I've never understood why so many of them are out there without tight U.S. Food and Drug Administration (FDA) regulation. So, I think that's a place to begin.   If you think back to the old breast cancer days when there was immunohistochemistry and a bunch of molecular technologies, the outcomes were so varied when compared on common tumor samples. So, we just seem to be quite comfortable to make the same set of mistakes again. I do think there are responsible investigators doing excellent work in the space, so I'm not critical of the space. I'm answering the question, which is we need now to bring some regulation in to ensure that the quality of the work, reproducibility of the work. You'll even see, and I know you and I have talked about this in the past, there'll be Mr. X who has prostate cancer and gets his PSA measured, which is Prostate-Specific Antigen, looking at how active the cancer is regularly in different labs. That makes absolutely no sense. There's no common standard. PSA in my lab is going to be different from PSA in your's. And so there just should be some nice, simple rules of how to use molecular testing in an optimized fashion.   Dr. John Sweetenham: Yeah, and I wonder also whether we need to be looking a little bit more closely at point of care clinical decision support for some oncologists who may not be as molecularly literate as others because I do think that's another real challenge at the moment is giving guidance to everyone who might see these patients in terms of treatment selection.   Dr. Derek Raghavan: Well, I agree with you completely. I mean, kudos to the major companies because most of them provide pretty good decision support. One with which we worked tended to be a little too positive about its product, and we worked to change that. And now they're actually very useful. We have a big series from our molecular tumor board here that runs over I think a 5-year period that Carol Farhangfar, PhD, has just submitted for publication, which shows that you can heavily influence people who are out in the community by providing centralized support for their use of molecular diagnostic tests. But again, we only deal with the major companies so that we think there's good quality control there. And we don't flip back and forth in an individual patient between one company and another.   Dr. John Sweetenham: Right. Well, I think we're almost out of time, Derek, but I did want to ask you one more question, and it's a real change of gear. But over the last year or so, I think that probably largely because of the COVID-19 pandemic, we have seen some exacerbation of workforce issues in the oncology workforce that we knew already existed. I think there is undoubtedly more burnout being reported than there was before. Certainly, within our own organization, we have seen some increased staff turnover and a number of people who I think, frankly, have realized that they want to move closer to their families.   And so, there's been a certain amount of churn, which I think many of us in cancer centers are experiencing. Interested to know whether you've seen anything similar and what strategies you're using in terms of staff retention and oncology clinician burnout at your center.   Dr. Derek Raghavan: I think this is a difficult problem. The morale at the Levine Cancer Institute, much like the Simmons Cancer Center, is high, and that's driven by the leadership cadre being out there with their troops, visible and actively engaged so that the troops on the line feel that the bosses are part of the deal. And we do silly little things that matter, which is parties and celebrations and thank yous and all that sort of stuff. We get the staff to thank each other. We encourage the patients to thank the staff just with an attaboy or something that just says we appreciate the care.   So, I think this is a challenge. I do think work-life balance in old geezers like you and me has been a slightly different thing from some of the younger physicians who are spending, I think sensibly, more time with their families and don't want to spend these long hours. I think the other thing is there is still a town-gown issue where there are people who can make a lot more money much more quickly in some parts of non-academic practice, and it's getting harder to publish in academic practice, so the rewards for that are slipping a little.   I actually don't really have a solution. I think that the august colleges drawing to the attention of the world that this is a big deal and engaging bipartisan support from the political machinery will be important. I think ASCO can, through its government relations people (ASCO Advocacy), continue to prosecute these issues, which they do. I think there is the mistake that we make in the cancer space is we do still tend to compete between societies.   I've always thought it would be much healthier to have ASCO, ASTRO, ACS, SUO, SSO and all those people having a common council that speaks on this sort of issue with one voice and draws to attention of the people out there that this is a big issue. The best of the doctors (docs) are getting older. The younger docs come through the Taylor laws are less experienced and less well-trained and have a different ethos. So, we're going to lose an aspect of practice that's been part of the tradition of medical practice since the time of Osler, and it's definitely going away.   I have a superb physician fellow working with me at the moment who I would rate as one of the best 3 in 10 years. The reason she's one of the best 3 in 10 years is she practices the style of medicine that my fellows did 25, 30 years ago, most of whom are now professors of medicine somewhere. And good with patients, knows her staff, does research, and somehow manages to have reasonable time for a family. That tradition is starting to go away, and I don't think there is a simple change. And then the final point, the people who run health care today see it as a business. I was in a meeting recently outside my own domain where someone said, you know, I have to figure out whether medicine is really importantly a health care business or whether it's an IT business focused on health care. And that's going to start to lose the human side of medicine. We spent some time on that today. The outcomes will go down if this is just a business.   Dr. John Sweetenham: Well, thanks, Derek. Really appreciate all of your insights today. I think there's no doubt that 2022 is going to be a year of many challenges for those of us in the oncology community and for our patients, but I think it's also inevitably going to be a very exciting year in terms of new developments.   And hopefully, if we're recording another podcast like this in a year from now, the COVID-19 pandemic will be a little bit more in the rearview mirror, and we will be able to focus on many of the other important issues that face us. So again, really appreciate your sharing your insights with us, and wish you all the best for 2022.   Dr. Derek Raghavan: John, always a pleasure chatting, and the same to you and Caroline and the family.   Dr. John Sweetenham: Thank you. And thanks to our listeners for your time today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclosures: Dr. John Sweetenham: Consulting or Advisory Role: EMA Wellness   Dr. Derek Raghavan: Consulting or Advisory Role: Gerson Lehrman Group, Caris Life Sciences   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on the podcast do not express the opinions of ASCO.  The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Guest host, Dr. Neeraj Agarwal, ASCO Daily News editor-in-chief and director of the Genitourinary Cancers Program at the University of Utah's Huntsman Cancer Institute, discusses the practice-changing KEYNOTE-564 and SWOG 1500 trials with Drs. Toni Choueiri and Sumanta "Monty" Pal. Dr. Choueiri is director of the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute and Dr. Pal is co-director of City of Hope's Kidney Cancer Program and associate editor of Cancer.Net. (This episode was recorded on 11/18/2021) Transcript Dr. Neeraj Agarwal: Hello, and welcome to the ASCO Daily News podcast. I am Dr. Neeraj Agarwal, the director of the Genitourinary Oncology Program, and the professor of Medicine at the University of Utah Huntsman Cancer Institute, and editor-in-chief of the ASCO Daily News. I'm delighted to welcome two internationally recognized leaders in the field, Dr. Toni Choueiri and Dr. Sumanta (Monty) Pal, for a discussion about two practice-changing studies in kidney cancer published this year-- KEYNOTE-564 and SWOG 1500. As a quick introduction, Dr. Choueiri is the director of Lank Center of Genitourinary Oncology at the Dana-Farber Cancer Institute. He's also the Jerome and Nancy Kohlberg Chair, and professor of medicine at the Harvard Medical School. Dr. Sumanta "Monty" Pal is a professor in oncology, and co-director of City of Hope's Kidney Cancer Program, and he is an associate editor of cancer.net of ASCO. Our full disclosures are available in the show notes. And disclosures relating to all episodes of podcasts can be found on our transcripts at ASCO.org/podcast. Toni and Monty, what a day it has been for our patients with kidney cancer. I woke up with the news of the U.S. Food and Drug Administration (FDA) approval of the first ever adjuvant immunotherapy for patients with renal cell carcinoma. It is so great to have you both on the podcast today.   Dr. Monty Pal: Glad to be here. Thanks, Neeraj.   Dr. Toni Choueiri: Thank you, Neeraj. So glad to be here.   Dr. Neeraj Agarwal: So, let me start by asking questions to you first, Toni. So, you recently published the primary results of the phase 3 KEYNOTE-564 study, showing the efficacy of adjuvant therapy with pembrolizumab and immune checkpoint inhibitor in patients with renal cell carcinoma. And this study led to the approval of pembrolizumab this morning. So, please tell us more about the study design and why did you do this study.   Dr. Toni Choueiri: Thank you, Neeraj. And thank you, really, ASCO for this wonderful podcast series. And a big hit, I always listen to them when I'm driving or jogging. And really, thanks for this opportunity because kidney cancer adjuvant therapy has been something like a holy grail we're trying to find for a long, long time. The first adjuvant trial, a randomized trial, in renal cell cancer was in 1973 with radiation therapy. And since that time, all the trials except for one have been a complete failure in a way. And the first adjuvant immunotherapy trial was with old immunotherapy cytokine that we don't use much anymore and was in 1992. I was not done with medical school. I was not actually done with high school at that time, let alone medical school. And now that we have, as we all know, a revolution in the oncology field through these immune checkpoint inhibitors that reinvented immunotherapy in cancer, and now that pembrolizumab has shown activity in patients with more advanced disease, we thought about taking this into the adjuvant setting, a setting of patients where they were subjected to surgery. But on the pathology report, we knew that their risk of this cancer coming back, of recurrence, is somewhat intermediate high or high. These are patients that have stage 2 but grade 4, stage 3, D3, D4. These are patients that had node-positive resected. And we took even patients where the kidney is out, but, also, they had a removal of a metastatic site--let's say a lung metastasis--within a year of removing the kidney. And we know these patients we refer to as M1NED are at quite high risk of recurrence. And we randomly assigned 994 patients to receive pembrolizumab for a year versus placebo. And after a median follow-up of only 2 years--so I want to insist here that this is short for any trial in general--we saw a decrease in the risk of recurrence or death. The hazard ratio for disease-free survival was 0.68. So, a 32% decrease in the risk of recurrence or death. We looked at safety, and we already are familiar in the field of GU oncology with pembrolizumab. And we didn't see when we looked at the safety profile any surprises, any enhanced toxicity. Of course, immune-related adverse events are the number one concern with pembrolizumab. There were no deaths on trial related to pembrolizumab. We saw around 7% of patients needing high dose steroid to medicate these immune-related adverse event, and some patients had to come off therapy for that. We also took a look, Neeraj, an early look, at overall survival. We only had 25% of events, 51 deaths. And we did not meet the very rigorous statistical significance that is needed to say that study is positive for overall survival. But the hazard ratio was 0.54, a 46% decrease in the risk of death, which is kind of encouraging. And after a year, the curve starts to separate. Before a year, they're not separating. And that is consistent with prior studies in general.   Dr. Neeraj Agarwal: This is a very interesting point you just raised, that DFS, disease-free survival, is strongly positive. And even overall survival is trending in the right direction, right?   Dr. Toni Choueiri: Correct.   Dr. Neeraj Agarwal: That's great. So obviously, I would like to raise another point here. When we talk about adjuvant study, we usually think about a localized kidney cancer, which is removed by the surgeon, and then [the] patient is coming to see us for treatment in adjuvant setting. But this study, I would like to highlight, as you said, also included patients who had oligometastatic disease, had successful surgical removal of the oligometastatic disease, and they were also eligible for this trial.   Dr. Toni Choueiri: Yes, absolutely. And I think this is somewhat on the recent side in clinical trials in kidney cancer. The reason for that is that, in practice, we see those patients. And we even had two small trials in the TKI era with sorafenib and pazopanib, small studies, were also completely negative. So, we thought here that we should not exclude these patients. They end up being 6%, 7% of all participants, but this remains an area of unmet medical need.   Dr. Neeraj Agarwal: So, how is the hazard ratio in those patients who had metastatic disease removed and then treated with pembrolizumab?   Dr. Toni Choueiri: Yeah, it was very low. It was 0.2, so 0.29. And this was great to see. I don't want to go into really over-interpreting these results. All the hazard ratio--when you look at subgroup analysis or in the forest plot, all the hazard ratio are less than 1. We didn't see something--let's say 1.5--in favor of pembrolizumab. Now you go into a smaller subgroup, then your confidence intervals are very large and hard to interpret, except that to say, look, on average there could be a significant benefit here, but we can't tell.   Dr. Neeraj Agarwal: Sure, absolutely. I agree with you. So, how this is going to affect the current treatment paradigm, which is for patients with newly diagnosed metastatic RCC, where combination of VEGF-TKI plus immunotherapies (IOs) or IO/IO combinations have become standard of care or treatment paradigm?   Dr. Toni Choueiri: I do believe it will be a standard of care currently in the right population. There are a lot of unanswered questions, but that will be answered hopefully with more follow up. We have already, beside these results, reported--so these results were reported in the plenary session at the 2021 ASCO [Annual Meeting]. But later on, another analysis dealing with patient-reported outcome and quality of life was reported at ESMO and also showed no detriment in quality of life--that's the voice of the patient--no detriment with pembrolizumab (pembro). There is a lot still to do and a lot of unanswered questions, such as the non-clear cell histology, those patients who had surgery of their metastatic disease more than a year. But most important, I think, two questions. One, how can you know from the get-go who are the patients that need adjuvant pembrolizumab? We do not have any valid ctDNA. And I know Dr. Pal was involved with a lot of these type of research. We don't have any ctDNA test that is really that faithful and sensitive in the MRD space in renal cell. Many of us are working, so we don't know. We may end up over-treating patients that need surgery only. And actually, we may end up under-treating patients that need, perhaps, pembro, and another drug. And the second thing in those patients--and I hope it does not happen, but unfortunately, it will to some extent--whose tumor progress on adjuvant pembrolizumab, what do you do? What's the treatment paradigm? And actually, there is no data. This is a data-free zone. And I would think somebody whose tumor progressed, tumor continued to grow or grows, while they're actively on pembrolizumab, on IO, is way different than someone whose tumor comes back after 2 or 3 years from stopping the drug. Should we treat them with the same drug? Should we treat them with the TKI plus IO? Luckily, there are trials that are ongoing in patients whose tumor progressed after PD-1/PD-L1 inhibitor to give them a TKI as a control arm, or a TKI plus an immune checkpoint inhibitor. And I know Dr. Pal is very heavily involved with such trials. So, hopefully, we will answer this question, but not anytime soon.   Dr. Neeraj Agarwal: Very interesting, and definitely new results are posing new challenges in how we practice medicine here in the coming future. So, Monty, you are leading a trial with a very similar trial with atezolizumab. And I'm really hoping, we are all really hoping, that we see the other trial being positive, so we have more treatment options for our patients.   Dr. Monty Pal: I couldn't agree with you more. I mean, I definitely think that Toni's study really adds a lot of fuel to the fire suggesting that this strategy of adjuvant immunotherapy may be successful in localized renal cell.   Dr. Neeraj Agarwal: And I'm not going to really delve into the side effects of pembrolizumab and atezolizumab because these drugs are used quite often. They are in widespread use for different types of cancer. But just a quick question, any safety signal, Toni? Did you see any safety signal with pembrolizumab in this patient population?   Dr. Toni Choueiri: Yeah, this is an excellent question. So, nothing that would be different than using pembrolizumab overall knowing in other diseases as a single agent. So, this drug not first in human, as you know, and it's been approved in combination or as a single agent in many diseases. A tumor that the three of us treat is bladder cancer, and we know from another study how to use pembrolizumab. I think that the use of corticosteroid is somewhat of an objective way, at least to me, in looking at immune-related adverse event. And it has been between 5% to 10%, so we're not way off here. But there is no doubt that there are patients that we had no death on trial attributed to drug that may have, with pembrolizumab, some serious toxicities. We had patients that had autoimmune diabetes, hypophysitis, pneumonitis--quite uncommon, but not impossible.   Dr. Neeraj Agarwal: We'll still need to keep an eye for that, basically.   Dr. Toni Choueiri: No doubt.   Dr. Neeraj Agarwal: Yes. So, changing gears, let's talk to you, Monty. You recently presented the primary results of the SWOG 1500 trial in patients with metastatic non-clear cell renal cell carcinoma. Could you please tell us why you did this study and how this study's design was unique compared to similar studies in this setting?   Dr. Monty Pal: Yeah. No, absolutely. Toni did a great job of outlining areas that are sort of free of data in the adjuvant space, particularly with immunotherapy. I think that data-free area for us in kidney cancer for a long time has been non-clear cell histology. We just don't really know how to treat them. And I actually got advice from Toni when I was devising SWOG 1500. We planned it out as a very simple study comparing sunitinib and cabozantinib. And Toni will remember this history well. It sort of went through several iterations. The study blossomed into a six-arm trial. Ultimately, it turned into a four-arm study, looking at sunitinib versus cabozantinib versus two other MET inhibitors--savolitinib and crizotinib. And ultimately, the study was boiled down to essentially what we'd originally proposed. Two of the MET inhibitors--savolitinib and crizotinib--failed to surpass that initial analysis for PFS. So, ultimately, we demonstrated a superiority with cabozantinib over sunitinib for progression-free survival.   Dr. Neeraj Agarwal: So, what is the current treatment paradigm for patients who have newly diagnosed metastatic papillary RCC now?   Dr. Monty Pal: I think for patients who don't have genomic selection, I think that cabozantinib remains the standard. I really want to champion- and maybe Toni can talk a little bit more about this--a study that Toni is leading called the SAMETA trial, which I think has a really innovative design. And it's going to be genomically characterizing patients and randomizing to savolitinib with durvalumab or sunitinib. Tell me, Toni, if I have the design right there.   Dr. Toni Choueiri: Yes. Actually, this is a specific study in a specific population. It's not in papillary RCC as much as in those 30%, 40% of papillary RCC that have MET-driven tumors, so MET alteration, whether through chromosome 7 duplication, through chromosome 7 trisomy, through mutation or amplification. These patients will get either control arm or they will get savolitinib, which is a pure MET inhibitor that is devoid of VEGF-related toxicities, savolitinib plus durvalumab, or durvalumab alone. So, two experimental arms and one control. And the reason for this is we saw activity and quite a good toxicity profile with savolitinib, a pure MET inhibitor, over sunitinib in an earlier trial that was sunitinib against savolitinib in selected patient populations. The study had to close early. So, despite the numerical difference, this was not statistically significant. And then in another study led by Dr. Powles and colleagues, there was also some interesting activity how durvalumab could augment that activity. So, we're launching a phase 3 trial with three arms that you described very well.   Dr. Neeraj Agarwal: That's wonderful. So, what are the next steps, Monty? I mean, this is amazing to see you designing an investigator-initiated trial. This was your concept. You designed it. You built this to be a huge multicenter trial, which was open across the country, funded by the National Cancer Institute. And congratulations for making that happen. It's rare for us to see these trials going from a concept stage to a national trial, and then changing the standard of care. So, what are the next steps now for you and your team in SWOG for papillary RCC or metastatic papillary RCC? How do you build out further with the backbone of cabozantinib?   Dr. Monty Pal: I really appreciate the question, Neeraj. It's so critical to understand that we're just not quite done yet. Toni's study, as I've mentioned, is incredibly innovative. I'm also really thrilled to be working with someone who you've mentored so well, Ben Maughan, at the Huntsman Cancer Institute in Utah. And he's actually designed a brilliant study, which we're going to be leading together, which looks at cabozantinib with or without atezolizumab. Recently, in a study that you and I and Toni were a part of that we just published in JCO, we actually saw quite impressive response rates with the combination of cabozantinib and atezolizumab in patients with papillary RCC, around 47%. Those response rates were actually replicated in a separate study run by Joe Lee at Memorial Sloan Kettering. In the context of papillary disease response rates were again above a threshold of around 40%. So, I think there's something to it. But until we really subject this to randomization, I think we're not going to know whether or not cabo plus IO is standard. So, I encourage everyone to consider Toni's study. I encourage everyone to look out for our trial of cabo plus or minus atezo, which should be rolling out next year.   Dr. Neeraj Agarwal: What is the name of the trial, or the number, for our audience?   Dr. Monty Pal: Yeah, we lucked out with another great number. We got 1500 for the first trial. This is going to be SWOG 2200. So SWOG 2200, and I think it's due to open maybe in the first quarter of 2022.   Dr. Neeraj Agarwal: That's fantastic news. Any new signal? We know cabozantinib is already approved for our patients with metastatic RCC, courtesy METEOR trial led by Dr. Choueiri. Toni, it's amazing to see how many times you have changed standard of care for our patients with metastatic RCC. So, any new safety signal of cabozantinib in this patient population with metastatic papillary RCC?   Dr. Monty Pal: Nothing that appreciated. The toxicity profile was pretty much on par with what you'd anticipate for cabozantinib in the setting. Major side effects were hypertension, hand-foot syndrome, [and] diarrhea. Nothing that really sort of stood out relative to what we would expect in a clear cell population of patients.   Dr. Neeraj Agarwal: That's great. Any final messages for our patients, for our audience, for our listeners?   Dr. Toni Choueiri: Well, let me start, and maybe Monty can add. It's been, and it hopefully will continue to be, this humbling experience, where median survival from metastatic RCC in mid-2000--not long time ago during our training--has been 1 year. And now in metastatic disease, it's 4 to 5 years. And that is only going to get better. And then it's even more humbling to be in a time where you can talk about adjuvant treatment in this disease, renal cell cancer, that continues every year to kill, unfortunately, 14,000 Americans. That's just in the U.S. alone. So, we have to continue in getting more targets, more drugs, more reasonable combination, and the right patient, whether through specific biomarker that are tissue or blood-based or specific liquid biopsies that can tell you who has and who doesn't have cancer at the microscopic levels.   Dr. Neeraj Agarwal: Thank you. How about you, Monty? Any final message for our audience?   Dr. Monty Pal: I couldn't have summarized it better than Toni, just such a wonderful statement around optimism for what we've achieved so far and what's yet to come. And if I could emphasize to anyone in the audience today the need to keep progressing the field further with clinical trials, I think that would be my underlying message.   Dr. Neeraj Agarwal: Thank you again, Toni, Monty, for your valuable insights and thoughts. Thank you for all the inspiration. This is indeed so inspiring to see your work, which is changing the lives of our patients on a daily basis. Our listeners will find links to your studies in the transcript of this episode. I wish you all the best.   Dr. Toni Choueiri: Thank you.   Dr. Neeraj Agarwal: And thank you to our listeners for your time today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts. Thank you so much.   Disclosures: Dr. Neeraj Agarwal: Consulting or Advisory Role: Pfizer, Medivation/Astellas, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Exelixis, Pfizer, Merck    , Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Foundation Medicine, Gilead Sciences Research Funding (inst.): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, ORIC Pharmaceuticals, crispr therapeutics, and Arvinas   Dr. Sumanta (Monty) Pal: Consulting or Advisory Role: F. Hoffmann LaRoche, F. Hoffman Research Funding (inst.): Eisai, Genentech, Roche, Exelixis, Pfizer Travel, Accommodations, Expenses: Genentech, Seattle Genetics   Dr. Toni Choueiri: Employment: Dana Farber Cancer Hospital Leadership: Dana Farber Cancer Hospital, NCCN, KidneyCan, ASCO, ESMO Stock and Other Ownership Interests: Pionyr, TEMPEST Honoraria: NCCN, UpToDate, Michael J. Hennessy Associates, ASCO, Harborside Press, Analysis Group,                AstraZeneca, Alexion Pharmaceuticals, Sanofi/Aventis, Bayer, Bristol-Myers Squibb, Genentech/Roche, GlaxoSmithKline, Merck          , Novartis, Peloton Therapeutics , Pfizer, Corvus Pharmaceuticals, Ipsen,                 Foundation Medicine, Eisai, PlatformQ Health, Clinical Care Options, Navinata Healthcare, Kidney Cancer Journal, Exelixis, Prometheus, Lpath, NEJM, Lancet Oncology, Cerulean Pharma, alligent, EMD Serono, HERON, Lilly, Janssen Oncology, IQvia, Aveo, and NCI. Consulting or Advisory Role: Pfizer, Bayer, Novartis, GlaxoSmithKline, Merck, Bristol-Myers Squibb, Roche/Genentech, Eisai, Foundation Medicine, Cerulean Pharma, AstraZeneca, Exelixis, Prometheus Laboratories, alligent, Ipsen, Corvus Pharmaceuticals, Lpath, Alexion Pharmaceuticals, Sanofi/Aventis, Peloton Therapeutics, UpToDate, NCCN, Michael J. Hennessy Associates, Analysis Group, Kidney Cancer Journal, Clinical Care Options, Paltform Q, Navinata Healthcare, Harborside Press, ASCO, NEJM, Lancet Oncology, EMD Serono, HERON, Lilly, ESMO, NiKang Therapeutics, Kanaph Therapeutics, Infinity Pharmaceuticals, and Aravive Research Funding (inst.): Pfizer, Novartis, Merck, Exelixis               , TRACON Pharma, GlaxoSmithKline, Bristol-Myers Squibb, AstraZeneca, Peloton Therapeutics, Roche/Genentech, Celldex, Agensys, Eisai, Takeda, Prometheus, Ipsen, Corvus Pharmaceuticals, Cerulean Pharma, Seattle Genetics/Astellas, Bayer, Foundation Medicine, Roche, Calithera Biosciences, Analysis Group, NCI, GATEWAY for Cancer Research, and Congressionally Directed Medical Research Programs (DOD) Patents, Royalties, Other Intellectual Property (inst.): International Patent Application No. PCT/US2018/058430, entitled “Biomarkers of Clinical Response and Benefit to Immune Checkpoint Inhibitor Therapy, International Patent Application No. PCT/US2018/12209, entitled “PBRM1 Biomarkers Predictive of Anti-Immune Checkpoint Response Patents, Royalties, Other Intellectual Property: ctDNA technologies Travel, Accommodations, Expenses: Pfizer, Bayer, Novartis, GlaxoSmithKline, Merck, Bristol-Myers Squibb, Roche/Genentech, Eisai, Foundation Medicine, Cerulean Pharma, AstraZeneca, Exelixis, Prometheus, alligent, Ipsen, Corvus Pharmaceuticals, Lpath, Alexion Pharmaceuticals, Sanofi/Aventis, UpToDate, Peloton Therapeutics, NCCN, Michael J. Hennessy Associates, Analysis Group, Kidney Cancer Journal, Clinical Care Options, PlatformQ Health, Harborside Press, Navinata Healthcare, NEJM, Lancet Oncology, EMD Serono, HERON, Lilly, and ESMO Other Relationship: Medical writing and editorial assistance support may have been funded by Communications companies funded by pharmaceutical companies such as ClinicalThinking, Health Interactions, Envision Pharma Group, Fishawack Group of Companies, Parexel   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.    

Guest host Dr. Neeraj Agarwal, editor-in-chief of ASCO Daily News and director of the Genitourinary Cancers Program at the University of Utah Huntsman Cancer Institute, interviews Dr. Oliver Sartor, medical director of the Tulane Cancer Center in New Orleans, on the practice-changing VISION trial and its impact on the current treatment paradigm for mCRPC. Transcript ASCO Daily News: Welcome to the ASCO Daily News Podcast. Our topic today is the practice-changing VISION trial, a phase III trial of radioligand therapy in patients with metastatic castration-resistant prostate cancer. Our guest host, Dr. Neeraj Agarwal, the editor-in-chief of the ASCO Daily News and director of the Genitourinary Cancers Program at the University of Utah's Huntsman Cancer Institute, will speak with one of the trial's investigators, Dr. Oliver Sartor, the medical director of the Tulane Cancer Center and Laborde Professor for Cancer Research. Their full disclosures are available on the transcript of this episode, and disclosures relating to all episodes of the Daily News Podcast are available on our transcripts at asco.org/podcasts.   Dr. Neeraj Agarwal: Hi, my name is Dr. Neeraj Agarwal. I am with Dr. Oliver Sartor. Today, we are going to discuss one of the practice-changing trials in the context of metastatic castration-resistant prostate cancer. Welcome to the ASCO Daily News Podcast, Dr. Sartor. Thanks for taking the time to be with us today.   Dr. Oliver Sartor: Thank you, Neeraj. A pleasure to be here.   Dr. Neeraj Agarwal: You recently published the primary results of the phase III VISION trial, which tested the efficacy of a novel radioligand therapy, Lutetium-177-PSMA-617, in men with metastatic castrate-resistant prostate cancer. Could you please tell us more about this compound and why you did this study?   Dr. Oliver Sartor:  So I'll start off with the compound itself. Radioligand therapy is a therapy that has a little warhead, and that warhead in this case is Lutetium-177. But it's guided by binding to PSMA. Now, PSMA is prostate-specific membrane antigen, and many of us are familiar with it, but some may not be. So PSMA is a protein expressed on the surface of most prostate cancer cells. Not all patients have it, but most do. And the ability of the PSMA Lutetium-177 to target the cancer was indicated in some preliminary studies, but they have not been to phase III. So the purpose of the phase III VISION trial was really to design a definitive study to look at overall survival, in particular, to determine whether or not this agent was truly active. And the good news is, it is truly active. And in the VISION trial, we were able to not only extend life with an overall survival benefit, haz ratio 0.62, but there was also a time-to-progression image-based radiographic progression-free survival. It was also much in favor of the PSMA Lutetium with a haz ratio of 0.4. So whether or not you look at time to cancer progression or whether or not you look at overall survival, this is an effective therapy. It, of course, does have some adverse side effects. We can talk more about that, but it's reasonably well tolerated. And I do anticipate that there'll be an FDA approval as a consequence of these pivotal findings.   Dr. Neeraj Agarwal: These are wonderful results and news for our patients. Please tell me how it will affect the current treatment paradigm of our patients with mCRPC. As we know, you selected patients who had disease progression on chemotherapy with taxanes and novel hormonal therapy. But real-world studies, many of which were published by you, have shown that docetaxel is received by a minority of patients with metastatic prostate cancer. So how do you envision treating your patients who do not want to be treated with chemotherapy as many of my patients do? How will you apply Lutetium-177 in their treatment?   Dr. Oliver Sartor:  Well, Neeraj, I think that we're going to be restricted in accordance with the label that the FDA provides. And I fully expect that the label will include a progression after treatment with docetaxel or at least one taxane-based therapy because that's the way the VISION trial was constructed. Now, you're raising a very critical point, and that is, what about the individuals that do not want to receive or are ineligible to receive a chemotherapy such as docetaxel? And for those individuals, we now have a new trial called PSMA4, and that trial is going to be testing the Lutetium-177-PSMA-617 in the context of chemotherapy-naive patients. So I think we're going to have to wait until we have more results, more clinical trials completed, prior to the application of PSMA-617 into the more general population of chemotherapy-naive patients. But those clinical trials are now underway.   Dr. Neeraj Agarwal: That's great. So, Oliver, in the VISION trial, you did mandate a diagnostic PSMA PET scan, and patients who were positive on the diagnostic PSMA PET scan were deemed to be eligible for enrollment on the VISION trial. Do you expect FDA to include diagnostic PSMA scan for eligibility for treatment with the Lutetium-177 in the real-world setting? If it doesn't or if it does, how it is going to affect the treatment of our patients, that availability of treatment for our patients?   Dr. Oliver Sartor:  That's really a great question. And I do expect that PSMA PET imaging will be a criteria given that it was used for patient selection. Now, as it turned out, about 87% of the patients actually did qualify after getting a PSMA PET scan. And given that that was part of the inclusion criteria, I anticipate that the FDA will also incorporate such imaging. Now, it does get to be a bit of an issue because it turns out that PSMA PET is just now coming into more widespread use. We did have, in May of this year, the approval by the FDA for the PSMA PET imaging agent and-- I shouldn't say "the"-- a PSMA PET imaging agent. Prior to that, in December of last year, there was both UCLA and UCSF approval by the FDA for yet another PSMA PET imaging agent. As we move forward, I anticipate that PET imaging is going to be more widely available. And of course, we don't have the approval as of yet today for the PSMA-617-Lutetium-177. And when we do get the anticipated approval, which likely will be in 2022, then I also anticipate that PSMA PET will be more widely available. Now, there are still issues with reimbursement for PSMA PET, and we've encountered those in our own practice. But that's a rapidly changing area, and we're working with the insurance companies in an effort to ensure that patients will get the imaging that they need.   Dr. Neeraj Agarwal:  Got it. And obviously, I asked this question because many of my community friends and colleagues have asked me this question.  Before we talk about the side effects of Lutetium-177, would you have any message for our friends and colleagues in the community who are bracing themselves for treating their patients with the Lutetium-177, whether they should be proactive in establishing contacts and relationships with the nuclear medicine facilities and so on?   Dr. Oliver Sartor:  That's a great question, Neeraj, because I think you're raising a very important point. This is going to be the type of therapy that involves multidisciplinary care. We can see that there'll be diagnostic PET imaging as being a component of the study. There'll be the necessity of licensed physicians, typically either nuclear medicine or radiation oncology, to actually administer the drug. And then, quite frankly, the medical oncologists or those urologists who are trained in advanced prostate cancer are going to need to manage the patient. This is a lot more than just getting an injection. Many of these patients are ill. They need to have symptom management. They need to manage their bone health. They need to manage their hormonal manipulations. They need management with regard to pain. So this is not just about giving an injection. And I encourage those people who are interested to involve multidisciplinary teams starting now. And I realize that the therapy is not available now, but you have to anticipate that it will be. And I think it will be a game changer of a therapy, and many patients are going to want it. So that means it's incumbent upon the physicians to be prepared, and that means multidisciplinary care.   Dr. Neearj Agarwal:  Excellent point. So basically, we should be ready. We should start establishing relationships with nuclear medicine facilities or radiation oncologists who are going to deliver Lutetium-177. Overall, when I was reading the New England Journal paper, the side effect profile seemed very reasonable. I did not see any red flags. To me, it sounded like a pretty well-tolerated drug. So what is your take on the side effects of Lutetium-177?   Dr. Oliver Sartor: I think the side effects are quite manageable. One of the unique side effects is that of dry mouth and that's because the PSMA can actually be expressed in the salivary glands and that there is some potential for salivary gland binding in the PSMA-617-Lutetium. And that means that you can have damage to the salivary glands, and that means dry mouth. It turns out that a little over 40% of the patients actually did complain of a dry mouth, and that needs to be managed typically with fluid intake or various ways of mouth moisturizers. Fatigue is a potential issue. It was raised, as well as some bone marrow suppression. And if you look at the grade 3/4 toxicities, anemia was present a little more than 10% of the time. And that, of course, needs to be monitored. There is some potential collateral damage to the bone marrow. So these patients need to have their counts monitored. They need to have their symptoms assessed. And they need to be managed as they go through the process. It's not just about giving an injection, but clearly, the licensed individuals, including nuclear medicine and radiation oncology, need to be engaged, because without them, there is no injection. So this is a complex multidisciplinary care paradigm. And emphasizing the point, symptom management, yes; adverse event management, yes. But you have to deliver the drug, and that means multidisciplinary care.   Dr. Neeraj Agarwal:  Those are fantastic points. Thank you very much, Dr. Sartor, for taking time to be with us. And I'm really hoping that this podcast will be very enriching to our listeners. Thank you very much.   Dr. Oliver Sartor: Thank you, Neeraj. Glad to be here.   ASCO Daily News:  You've been listening to Dr. Neeraj Agarwal of the Huntsman Cancer Institute and Dr. Oliver Sartor of the Tulane Cancer Center. Our listeners will find a link to the VISION study in the transcript of this episode. Thank you to our listeners for joining us today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclosures: Dr. Neeraj Agarwal Consulting or Advisory Role: Pfizer, Medivation/Astellas, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Exelixis, Merck, Novartis, Eisai,    Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences   Research Funding (Inst.): Bayer Your Institution, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen,    AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, crispr therapeutics, and Arvinas     Disclosures: Dr. Oliver Sartor Stocks & Other Ownership Interests: Lilly, GlaxoSmithKline, Abbvie, Cardinal Health, United Health Group, PSMA Therapeutics, Clarity Pharmaceuticals, Noria Therapeutics, Inc., Clovis Consulting or Advisory Role: Bayer, Sanofi, AstraZeneca, Dendreon, Constellation Pharmaceuticals, Advanced Accelerator Applications, Pfizer, Bristol-Myers Squibb, Bavarian Nordic, EMD Serono, Astellas Pharma, Progenics, Blue Earth Diagnostics, Myovant, Myriad Genetics, Novartis, Clarify Pharmaceuticals, Fusion, Istopen Technologien Meunchen, Janssen, Noxopharm, Clovis, Noria Therapeutics, Point Biopharma, TeneoBio, Telix, Theragnostics Research Funding (Inst): Sotio, Janssen, Progenics, Bayer, Sanofi, Endocyte, Merck, Invitae, Constellation Pharmaceuticals, Advanced Accelerator Applications, Dendreon, AstraZeneca Expert Testimony: Sanofi Travel, Accommodations, Expenses: Bayer, Johnson & Johnson, Sanofi, AstraZeneca, Progenics   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Dr. Oliver Sartor on the VISION Trial and Improving Care for Patients With mCRPC       ASCO Daily News: Welcome to the ASCO Daily News Podcast. Our topic today is the practice-changing VISION trial, a phase III trial of radioligand therapy in patients with metastatic castration-resistant prostate cancer. Our guest host, Dr. Neeraj Agarwal, the editor-in-chief of the ASCO Daily News and director of the Genitourinary Cancers Program at the University of Utah's Huntsman Cancer Institute, will speak with one of the trial's investigators, Dr. Oliver Sartor, the medical director of the Tulane Cancer Center and Laborde Professor for Cancer Research. Their full disclosures are available on the transcript of this episode, and disclosures relating to all episodes of the Daily News Podcast are available on our transcripts at asco.org/podcasts.   Dr. Neeraj Agarwal: Hi, my name is Dr. Neeraj Agarwal. I am with Dr. Oliver Sartor. Today, we are going to discuss one of the practice-changing trials in the context of metastatic castration-resistant prostate cancer. Welcome to the ASCO Daily News Podcast, Dr. Sartor. Thanks for taking the time to be with us today.   Dr. Oliver Sartor: Thank you, Neeraj. A pleasure to be here.   Dr. Neeraj Agarwal: You recently published the primary results of the phase III VISION trial, which tested the efficacy of a novel radioligand therapy, Lutetium-177-PSMA-617, in men with metastatic castrate-resistant prostate cancer. Could you please tell us more about this compound and why you did this study?   Dr. Oliver Sartor:  So I'll start off with the compound itself. Radioligand therapy is a therapy that has a little warhead, and that warhead in this case is Lutetium-177. But it's guided by binding to PSMA. Now, PSMA is prostate-specific membrane antigen, and many of us are familiar with it, but some may not be. So PSMA is a protein expressed on the surface of most prostate cancer cells. Not all patients have it, but most do. And the ability of the PSMA Lutetium-177 to target the cancer was indicated in some preliminary studies, but they have not been to phase III. So the purpose of the phase III VISION trial was really to design a definitive study to look at overall survival, in particular, to determine whether or not this agent was truly active. And the good news is, it is truly active. And in the VISION trial, we were able to not only extend life with an overall survival benefit, haz ratio 0.62, but there was also a time-to-progression image-based radiographic progression-free survival. It was also much in favor of the PSMA Lutetium with a haz ratio of 0.4. So whether or not you look at time to cancer progression or whether or not you look at overall survival, this is an effective therapy. It, of course, does have some adverse side effects. We can talk more about that, but it's reasonably well tolerated. And I do anticipate that there'll be an FDA approval as a consequence of these pivotal findings.   Dr. Neeraj Agarwal: These are wonderful results and news for our patients. Please tell me how it will affect the current treatment paradigm of our patients with mCRPC. As we know, you selected patients who had disease progression on chemotherapy with taxanes and novel hormonal therapy. But real-world studies, many of which were published by you, have shown that docetaxel is received by a minority of patients with metastatic prostate cancer. So how do you envision treating your patients who do not want to be treated with chemotherapy as many of my patients do? How will you apply Lutetium-177 in their treatment?   Dr. Oliver Sartor:  Well, Neeraj, I think that we're going to be restricted in accordance with the label that the FDA provides. And I fully expect that the label will include a progression after treatment with docetaxel or at least one taxane-based therapy because that's the way the VISION trial was constructed. Now, you're raising a very critical point, and that is, what about the individuals that do not want to receive or are ineligible to receive a chemotherapy such as docetaxel? And for those individuals, we now have a new trial called PSMA4, and that trial is going to be testing the Lutetium-177-PSMA-617 in the context of chemotherapy-naive patients. So I think we're going to have to wait until we have more results, more clinical trials completed, prior to the application of PSMA-617 into the more general population of chemotherapy-naive patients. But those clinical trials are now underway.   Dr. Neeraj Agarwal: That's great. So, Oliver, in the VISION trial, you did mandate a diagnostic PSMA PET scan, and patients who were positive on the diagnostic PSMA PET scan were deemed to be eligible for enrollment on the VISION trial. Do you expect FDA to include diagnostic PSMA scan for eligibility for treatment with the Lutetium-177 in the real-world setting? If it doesn't or if it does, how it is going to affect the treatment of our patients, that availability of treatment for our patients?   Dr. Oliver Sartor:  That's really a great question. And I do expect that PSMA PET imaging will be a criteria given that it was used for patient selection. Now, as it turned out, about 87% of the patients actually did qualify after getting a PSMA PET scan. And given that that was part of the inclusion criteria, I anticipate that the FDA will also incorporate such imaging. Now, it does get to be a bit of an issue because it turns out that PSMA PET is just now coming into more widespread use. We did have, in May of this year, the approval by the FDA for the PSMA PET imaging agent and-- I shouldn't say "the"-- a PSMA PET imaging agent. Prior to that, in December of last year, there was both UCLA and UCSF approval by the FDA for yet another PSMA PET imaging agent. As we move forward, I anticipate that PET imaging is going to be more widely available. And of course, we don't have the approval as of yet today for the PSMA-617-Lutetium-177. And when we do get the anticipated approval, which likely will be in 2022, then I also anticipate that PSMA PET will be more widely available. Now, there are still issues with reimbursement for PSMA PET, and we've encountered those in our own practice. But that's a rapidly changing area, and we're working with the insurance companies in an effort to ensure that patients will get the imaging that they need.   Dr. Neeraj Agarwal:  Got it. And obviously, I asked this question because many of my community friends and colleagues have asked me this question.  Before we talk about the side effects of Lutetium-177, would you have any message for our friends and colleagues in the community who are bracing themselves for treating their patients with the Lutetium-177, whether they should be proactive in establishing contacts and relationships with the nuclear medicine facilities and so on?   Dr. Oliver Sartor:  That's a great question, Neeraj, because I think you're raising a very important point. This is going to be the type of therapy that involves multidisciplinary care. We can see that there'll be diagnostic PET imaging as being a component of the study. There'll be the necessity of licensed physicians, typically either nuclear medicine or radiation oncology, to actually administer the drug. And then, quite frankly, the medical oncologists or those urologists who are trained in advanced prostate cancer are going to need to manage the patient. This is a lot more than just getting an injection. Many of these patients are ill. They need to have symptom management. They need to manage their bone health. They need to manage their hormonal manipulations. They need management with regard to pain. So this is not just about giving an injection. And I encourage those people who are interested to involve multidisciplinary teams starting now. And I realize that the therapy is not available now, but you have to anticipate that it will be. And I think it will be a game changer of a therapy, and many patients are going to want it. So that means it's incumbent upon the physicians to be prepared, and that means multidisciplinary care.   Dr. Neearj Agarwal:  Excellent point. So basically, we should be ready. We should start establishing relationships with nuclear medicine facilities or radiation oncologists who are going to deliver Lutetium-177. Overall, when I was reading the New England Journal paper, the side effect profile seemed very reasonable. I did not see any red flags. To me, it sounded like a pretty well-tolerated drug. So what is your take on the side effects of Lutetium-177?   Dr. Oliver Sartor: I think the side effects are quite manageable. One of the unique side effects is that of dry mouth and that's because the PSMA can actually be expressed in the salivary glands and that there is some potential for salivary gland binding in the PSMA-617-Lutetium. And that means that you can have damage to the salivary glands, and that means dry mouth. It turns out that a little over 40% of the patients actually did complain of a dry mouth, and that needs to be managed typically with fluid intake or various ways of mouth moisturizers. Fatigue is a potential issue. It was raised, as well as some bone marrow suppression. And if you look at the grade 3/4 toxicities, anemia was present a little more than 10% of the time. And that, of course, needs to be monitored. There is some potential collateral damage to the bone marrow. So these patients need to have their counts monitored. They need to have their symptoms assessed. And they need to be managed as they go through the process. It's not just about giving an injection, but clearly, the licensed individuals, including nuclear medicine and radiation oncology, need to be engaged, because without them, there is no injection. So this is a complex multidisciplinary care paradigm. And emphasizing the point, symptom management, yes; adverse event management, yes. But you have to deliver the drug, and that means multidisciplinary care.   Dr. Neeraj Agarwal:  Those are fantastic points. Thank you very much, Dr. Sartor, for taking time to be with us. And I'm really hoping that this podcast will be very enriching to our listeners. Thank you very much.   Dr. Oliver Sartor: Thank you, Neeraj. Glad to be here.   ASCO Daily News:  You've been listening to Dr. Neeraj Agarwal of the Huntsman Cancer Institute and Dr. Oliver Sartor of the Tulane Cancer Center. Our listeners will find a link to the VISION study in the transcript of this episode. Thank you to our listeners for joining us today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclosures: Dr. Neeraj Agarwal Consulting or Advisory Role: Pfizer, Medivation/Astellas, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Exelixis, Merck, Novartis, Eisai,    Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences   Research Funding (Inst.): Bayer Your Institution, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen,    AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, crispr therapeutics, and Arvinas     Disclosures: Dr. Oliver Sartor Stocks & Other Ownership Interests: Lilly, GlaxoSmithKline, Abbvie, Cardinal Health, United Health Group, PSMA Therapeutics, Clarity Pharmaceuticals, Noria Therapeutics, Inc., Clovis Consulting or Advisory Role: Bayer, Sanofi, AstraZeneca, Dendreon, Constellation Pharmaceuticals, Advanced Accelerator Applications, Pfizer, Bristol-Myers Squibb, Bavarian Nordic, EMD Serono, Astellas Pharma, Progenics, Blue Earth Diagnostics, Myovant, Myriad Genetics, Novartis, Clarify Pharmaceuticals, Fusion, Istopen Technologien Meunchen, Janssen, Noxopharm, Clovis, Noria Therapeutics, Point Biopharma, TeneoBio, Telix, Theragnostics Research Funding (Inst): Sotio, Janssen, Progenics, Bayer, Sanofi, Endocyte, Merck, Invitae, Constellation Pharmaceuticals, Advanced Accelerator Applications, Dendreon, AstraZeneca Expert Testimony: Sanofi Travel, Accommodations, Expenses: Bayer, Johnson & Johnson, Sanofi, AstraZeneca, Progenics   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Dr. Oliver Sartor on the VISION Trial and Improving Care for Patients With mCRPC       ASCO Daily News: Welcome to the ASCO Daily News Podcast. Our topic today is the practice-changing VISION trial, a phase III trial of radioligand therapy in patients with metastatic castration-resistant prostate cancer. Our guest host, Dr. Neeraj Agarwal, the editor-in-chief of the ASCO Daily News and director of the Genitourinary Cancers Program at the University of Utah's Huntsman Cancer Institute, will speak with one of the trial's investigators, Dr. Oliver Sartor, the medical director of the Tulane Cancer Center and Laborde Professor for Cancer Research. Their full disclosures are available on the transcript of this episode, and disclosures relating to all episodes of the Daily News Podcast are available on our transcripts at asco.org/podcasts.   Dr. Neeraj Agarwal: Hi, my name is Dr. Neeraj Agarwal. I am with Dr. Oliver Sartor. Today, we are going to discuss one of the practice-changing trials in the context of metastatic castration-resistant prostate cancer. Welcome to the ASCO Daily News Podcast, Dr. Sartor. Thanks for taking the time to be with us today.   Dr. Oliver Sartor: Thank you, Neeraj. A pleasure to be here.   Dr. Neeraj Agarwal: You recently published the primary results of the phase III VISION trial, which tested the efficacy of a novel radioligand therapy, Lutetium-177-PSMA-617, in men with metastatic castrate-resistant prostate cancer. Could you please tell us more about this compound and why you did this study?   Dr. Oliver Sartor:  So I'll start off with the compound itself. Radioligand therapy is a therapy that has a little warhead, and that warhead in this case is Lutetium-177. But it's guided by binding to PSMA. Now, PSMA is prostate-specific membrane antigen, and many of us are familiar with it, but some may not be. So PSMA is a protein expressed on the surface of most prostate cancer cells. Not all patients have it, but most do. And the ability of the PSMA Lutetium-177 to target the cancer was indicated in some preliminary studies, but they have not been to phase III. So the purpose of the phase III VISION trial was really to design a definitive study to look at overall survival, in particular, to determine whether or not this agent was truly active. And the good news is, it is truly active. And in the VISION trial, we were able to not only extend life with an overall survival benefit, haz ratio 0.62, but there was also a time-to-progression image-based radiographic progression-free survival. It was also much in favor of the PSMA Lutetium with a haz ratio of 0.4. So whether or not you look at time to cancer progression or whether or not you look at overall survival, this is an effective therapy. It, of course, does have some adverse side effects. We can talk more about that, but it's reasonably well tolerated. And I do anticipate that there'll be an FDA approval as a consequence of these pivotal findings.   Dr. Neeraj Agarwal: These are wonderful results and news for our patients. Please tell me how it will affect the current treatment paradigm of our patients with mCRPC. As we know, you selected patients who had disease progression on chemotherapy with taxanes and novel hormonal therapy. But real-world studies, many of which were published by you, have shown that docetaxel is received by a minority of patients with metastatic prostate cancer. So how do you envision treating your patients who do not want to be treated with chemotherapy as many of my patients do? How will you apply Lutetium-177 in their treatment?   Dr. Oliver Sartor:  Well, Neeraj, I think that we're going to be restricted in accordance with the label that the FDA provides. And I fully expect that the label will include a progression after treatment with docetaxel or at least one taxane-based therapy because that's the way the VISION trial was constructed. Now, you're raising a very critical point, and that is, what about the individuals that do not want to receive or are ineligible to receive a chemotherapy such as docetaxel? And for those individuals, we now have a new trial called PSMA4, and that trial is going to be testing the Lutetium-177-PSMA-617 in the context of chemotherapy-naive patients. So I think we're going to have to wait until we have more results, more clinical trials completed, prior to the application of PSMA-617 into the more general population of chemotherapy-naive patients. But those clinical trials are now underway.   Dr. Neeraj Agarwal: That's great. So, Oliver, in the VISION trial, you did mandate a diagnostic PSMA PET scan, and patients who were positive on the diagnostic PSMA PET scan were deemed to be eligible for enrollment on the VISION trial. Do you expect FDA to include diagnostic PSMA scan for eligibility for treatment with the Lutetium-177 in the real-world setting? If it doesn't or if it does, how it is going to affect the treatment of our patients, that availability of treatment for our patients?   Dr. Oliver Sartor:  That's really a great question. And I do expect that PSMA PET imaging will be a criteria given that it was used for patient selection. Now, as it turned out, about 87% of the patients actually did qualify after getting a PSMA PET scan. And given that that was part of the inclusion criteria, I anticipate that the FDA will also incorporate such imaging. Now, it does get to be a bit of an issue because it turns out that PSMA PET is just now coming into more widespread use. We did have, in May of this year, the approval by the FDA for the PSMA PET imaging agent and-- I shouldn't say "the"-- a PSMA PET imaging agent. Prior to that, in December of last year, there was both UCLA and UCSF approval by the FDA for yet another PSMA PET imaging agent. As we move forward, I anticipate that PET imaging is going to be more widely available. And of course, we don't have the approval as of yet today for the PSMA-617-Lutetium-177. And when we do get the anticipated approval, which likely will be in 2022, then I also anticipate that PSMA PET will be more widely available. Now, there are still issues with reimbursement for PSMA PET, and we've encountered those in our own practice. But that's a rapidly changing area, and we're working with the insurance companies in an effort to ensure that patients will get the imaging that they need.   Dr. Neeraj Agarwal:  Got it. And obviously, I asked this question because many of my community friends and colleagues have asked me this question.  Before we talk about the side effects of Lutetium-177, would you have any message for our friends and colleagues in the community who are bracing themselves for treating their patients with the Lutetium-177, whether they should be proactive in establishing contacts and relationships with the nuclear medicine facilities and so on?   Dr. Oliver Sartor:  That's a great question, Neeraj, because I think you're raising a very important point. This is going to be the type of therapy that involves multidisciplinary care. We can see that there'll be diagnostic PET imaging as being a component of the study. There'll be the necessity of licensed physicians, typically either nuclear medicine or radiation oncology, to actually administer the drug. And then, quite frankly, the medical oncologists or those urologists who are trained in advanced prostate cancer are going to need to manage the patient. This is a lot more than just getting an injection. Many of these patients are ill. They need to have symptom management. They need to manage their bone health. They need to manage their hormonal manipulations. They need management with regard to pain. So this is not just about giving an injection. And I encourage those people who are interested to involve multidisciplinary teams starting now. And I realize that the therapy is not available now, but you have to anticipate that it will be. And I think it will be a game changer of a therapy, and many patients are going to want it. So that means it's incumbent upon the physicians to be prepared, and that means multidisciplinary care.   Dr. Neearj Agarwal:  Excellent point. So basically, we should be ready. We should start establishing relationships with nuclear medicine facilities or radiation oncologists who are going to deliver Lutetium-177. Overall, when I was reading the New England Journal paper, the side effect profile seemed very reasonable. I did not see any red flags. To me, it sounded like a pretty well-tolerated drug. So what is your take on the side effects of Lutetium-177?   Dr. Oliver Sartor: I think the side effects are quite manageable. One of the unique side effects is that of dry mouth and that's because the PSMA can actually be expressed in the salivary glands and that there is some potential for salivary gland binding in the PSMA-617-Lutetium. And that means that you can have damage to the salivary glands, and that means dry mouth. It turns out that a little over 40% of the patients actually did complain of a dry mouth, and that needs to be managed typically with fluid intake or various ways of mouth moisturizers. Fatigue is a potential issue. It was raised, as well as some bone marrow suppression. And if you look at the grade 3/4 toxicities, anemia was present a little more than 10% of the time. And that, of course, needs to be monitored. There is some potential collateral damage to the bone marrow. So these patients need to have their counts monitored. They need to have their symptoms assessed. And they need to be managed as they go through the process. It's not just about giving an injection, but clearly, the licensed individuals, including nuclear medicine and radiation oncology, need to be engaged, because without them, there is no injection. So this is a complex multidisciplinary care paradigm. And emphasizing the point, symptom management, yes; adverse event management, yes. But you have to deliver the drug, and that means multidisciplinary care.   Dr. Neeraj Agarwal:  Those are fantastic points. Thank you very much, Dr. Sartor, for taking time to be with us. And I'm really hoping that this podcast will be very enriching to our listeners. Thank you very much.   Dr. Oliver Sartor: Thank you, Neeraj. Glad to be here.   ASCO Daily News:  You've been listening to Dr. Neeraj Agarwal of the Huntsman Cancer Institute and Dr. Oliver Sartor of the Tulane Cancer Center. Our listeners will find a link to the VISION study in the transcript of this episode. Thank you to our listeners for joining us today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclosures: Dr. Neeraj Agarwal Consulting or Advisory Role: Pfizer, Medivation/Astellas, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Exelixis, Merck, Novartis, Eisai,    Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences   Research Funding (Inst.): Bayer Your Institution, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen,    AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, crispr therapeutics, and Arvinas     Disclosures: Dr. Oliver Sartor Stocks & Other Ownership Interests: Lilly, GlaxoSmithKline, Abbvie, Cardinal Health, United Health Group, PSMA Therapeutics, Clarity Pharmaceuticals, Noria Therapeutics, Inc., Clovis Consulting or Advisory Role: Bayer, Sanofi, AstraZeneca, Dendreon, Constellation Pharmaceuticals, Advanced Accelerator Applications, Pfizer, Bristol-Myers Squibb, Bavarian Nordic, EMD Serono, Astellas Pharma, Progenics, Blue Earth Diagnostics, Myovant, Myriad Genetics, Novartis, Clarify Pharmaceuticals, Fusion, Istopen Technologien Meunchen, Janssen, Noxopharm, Clovis, Noria Therapeutics, Point Biopharma, TeneoBio, Telix, Theragnostics Research Funding (Inst): Sotio, Janssen, Progenics, Bayer, Sanofi, Endocyte, Merck, Invitae, Constellation Pharmaceuticals, Advanced Accelerator Applications, Dendreon, AstraZeneca Expert Testimony: Sanofi Travel, Accommodations, Expenses: Bayer, Johnson & Johnson, Sanofi, AstraZeneca, Progenics   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.    

Dr. Gabrielle Rocque, chair of the 2021 ASCO Quality Care Symposium, breast oncologist and health services researcher at the University of Alabama at Birmingham, and symposium chair-elect, Dr. Stephanie Wheeler, professor in the Department of Health Policy and Management at the University of North Carolina at Chapel Hill, discuss key interventions in quality care and compelling patient perspectives presented at #ASCOQLTY21. Transcript ASCO Daily News: Welcome to the ASCO Daily News podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. On today's episode, we'll discuss promising interventions to improve the quality of care for patients and survivors and other key takeaways from the 2021 ASCO Quality Care Symposium. I'm delighted to welcome the chair and chair-elect of the [ASCO Quality Care] Symposium, Dr. Gabrielle Rocque and Dr. Stephanie Wheeler, for this discussion. Dr. Rocque is a breast oncologist and health services researcher. She is also associate professor of medicine in the Division of Hematology and Oncology and Gerontology, Geriatrics, and Palliative Care at the University of Alabama at Birmingham. Dr. Wheeler is a professor in the Department of Health Policy and Management at the University of North Carolina at Chapel Hill. She also serves as associate director of community outreach and engagement at the UNC Lineberger Comprehensive Cancer Center. My guests' full disclosures are available in our show notes, and disclosures relating to all episodes of the podcast are available on our transcripts at asco.org/podcasts. Dr. Rocque and Dr. Wheeler, thanks for being on the podcast today. Dr. Gabrielle Rocque: Thank you for having us. ASCO Daily News: Dr. Wheeler, it was wonderful to have a hybrid event this year, with people participating in person in Boston and virtually. This is surely a sign of things to come. Can you tell us about some of the most important interventions in quality improvement that were presented at the [ASCO Quality Care] Symposium? Dr. Stephanie Wheeler: Absolutely, and thank you so much for hosting us. It was a really terrific [ASCO Quality Care] Symposium. And the fact that we had hybrid engagement from investigators all over the country and internationally was really exciting. There's a couple of intervention classes, if you want to call it that, that I think were particularly inspiring and interesting to me. The first were sets of interventions that focused on strategies to improve goals of care conversations and advanced care planning directives for patients with cancer or people with terminal illness in particular. And I just wanted to highlight a couple of those that I thought were particularly innovative. One was Abstract 8, which focused on using computer modeling and care coaches to increase advanced care planning conversations for people with advanced cancer. And this was presented by Dr. Divya Gupta. And it was just a wonderful example of how we can utilize technology and also care coaches. And in many cases, these don't necessarily have to be clinicians. They sometimes can be community health workers and others who can help direct those conversations and make it more comfortable for people living with advanced disease, and also their families, to consider next steps. In a similar vein, there were two other presentations--Abstract 1 delivered by Dr. Manali Patel and Abstract 2 delivered by Dr. Divya Parikh--that also utilized a similar model in a different care setting. And in those cases, the care settings ranged from VA to integrated health care settings. And we even had a conversation about how to do this work in community rural oncology practices. And I think that this kind of intervention has the potential for translation across a variety of settings. And the next steps are going to be figuring out exactly how to implement it in these settings. So, that's one class that I thought was particularly interesting. And I just want to highlight another group of interventions and studies that I found really innovative. And those were the presentations about hospital at-home models and how we can better deliver oncology care in the comfort of individuals' homes. And I thought Dr. Cardinale Smith did a great job from Mount Sinai describing the landscape of those interventions and the future for this kind of care delivery (“Overview of Programs and Ethics”). ASCO Daily News: Excellent. Great to hear about those promising new approaches. Dr. Rocque, the [ASCO Quality Care] Symposium captured many trends in quality care, including patient-reported outcomes measurement as an important way to monitor quality of care and patients' experiences. Can you highlight the studies that will help inform our listeners about how to integrate patient-reported outcomes into real-world settings? Dr. Gabrielle Rocque: Yeah. This was a major topic of the conference this year to think about how patient-reported outcomes are informative both in traditional research settings and in real-world settings. So, I was really intrigued by the Abstract 154 by Joy Jarnagin. And that abstract talked about how the changes in patient-reported outcomes actually had a very strong association with patients' treatment response, and in fact, was even more informative than those patients' tumor markers and I think show a novel way that patient-reported outcomes can be used. We also saw some more traditional abstracts on patient-reported outcomes. I'd like to highlight Abstract 152 by Valerie Lawhon, which really used patient-reported outcomes to identify patients' experience and their mental health outcomes during the COVID-19 pandemic, and I think provided us some really important insight into the experiences of our patients. And then as you mentioned, there is a lot of focus on real-world settings and how to transition from typical research patient-reported outcomes to a more broad scale implementation. And the session implementing PROs in oncology practice was really outstanding in terms of considering how this can be done. So, Dr. Terry Mulvey from Massachusetts General Hospital presented their experience on how to get these patient-reported outcomes into routine care, and what are some of the challenges associated with that, and how did they have to adapt to make sure that this was doable in real-world settings (“Challenges to Getting Started in a Practice Setting”). I was also impressed with the study by Dr. Raymond Osarogiagbon on the potential populations where there can be barriers of care and their study looking at an intervention in which they're implementing patient-reported outcomes over a wide variety of different practice types across the country (“Potential Populations Where This Can Be a Barrier to Care”). And I think these early insights also pointed us to future questions. Dr. Wynne Norton did a wonderful job of outlining some of the future questions that are likely to come up as we move into an era where patient-reported outcomes are a part of standard of care, and really think about how do we refine these for maximal benefit (“Overview of Current Strategies”). So, I think all of these sessions were highlighting the promise of patient-reported outcomes, as well as the future questions in this space. ASCO Daily News: Excellent. As a specialist in gerontology, geriatrics, and palliative care, please tell us about new approaches that oncologists should be aware of as they strive to provide high quality care for older patients and those receiving palliative care. Dr. Gabrielle Rocque: Absolutely. So, we've talked a bit about the patient-reported outcomes. And I think we'd be remiss in not highlighting the presentation on geriatric assessment--the presentations on the geriatric assessments into clinical practice by Dr. [Rawad] Elias (“Incorporating Geriatric Assessments Into Practice”). And I think this highlights another opportunity for us to move the field forward and take better care of our older adults. In terms of palliative care, there were multiple very informative abstracts. Dr. Wheeler has highlighted a few in the space of care guides or lay health coaches providing support in advanced care planning. In addition, we saw an interesting discussion of caregiver interventions for patients that are receiving--with cancer treatment by Dr. Nick Dionne-Odom (“Caregiver Interventions”). And I think it's important that we remember both the patients and the caregivers who are affected by cancer and by the amount of work that has to be done to support a patient with cancer going through their journey. ASCO Daily News: Absolutely, so important to remember caregivers and their needs and resources that could be available to them as well. Dr. Wheeler, financial toxicity is an enormous concern for many patients and their families, and the oncology care community has been trying for some time to figure out how best to address the concerns of patients and the health care system. Are there any new interventions that we should be aware of? Dr. Stephanie Wheeler: Yes, and I think that the [ASCO Quality Care] Symposium was an opportunity to hear about several of those. And some of them didn't make it onto the main stage but were featured in abstract sessions and poster sessions. So, as we're all well aware, financial toxicity is a multidimensional set of constructs that includes patients and their family's material out-of-pocket burden, as well as the psychological distress and potentially harmful care altering behaviors that financial hardship induces. And so, we continue to hear at the [ASCO Quality Care] Symposium multiple talks about the strain that patients are undergoing, including the non-medical hardship that's introduced by a cancer diagnosis. And that was really interesting, and I think important to document. But I think that where the field is moving is more towards interventions, both behavioral interventions and systems interventions, multilevel approaches to dealing with the hardship itself as well as the importance of policy. So, there were several abstracts that talked about the introduction of biosimilars and generics and how that affected price of many of the oncologic drugs available on the market. And frankly, the message is a bit discouraging. Prices continue to rise. And in some cases, the price increases are not limited to pharmacologic products. In some cases, we saw abstracts presenting the increased cost of surgery, of outpatient care appointments, and things like that as well. So, we're not going to fix the problem by managing drug pricing alone. In terms of patient and family-directed interventions, I thought that there were some interesting abstracts. I want to highlight a number 53--or excuse me, Abstract 43 by Melissa Beauchemin that focused on the existence of hospital specialty pharmacies and partnering with freestanding care coordination organizations to improve access to oncology medications, as well as Abstract 96 presented by Ms. Rachel Marquez which was focused on resolving transportation disparities and access to cancer treatments. These kinds of interventions are obviously patient directed but have tremendous potential. And then I also want to just note a couple of additional studies that are ongoing that are important to recognize in this field. There are at least five National Cancer Institute (NCI)-funded R01 trials underway right now investigating the role of financial navigation and various iterations of it in different care settings. So, I think we will want to look to this meeting as an opportunity to hear about that work as it moves forward. And how that work is implemented is going to be vital, because the types of care settings where it's being done--ranging from AYA populations in Utah, to urban populations in Washington state, to integrated care organizations in Northern California, all the way to parts of rural North Carolina--we're going to see a diversity of outcomes and different ways in which those types of interventions can manifest in those different studies. I also want to note that the NCI has funded a series of supplements through its Cancer Center Core Grant Initiative that are all focused on identification, timely identification of financial toxicity in practice. And many of the investigators leading that work were attending the [ASCO Quality Care] Symposium, and so that will be important to keep an eye on as we move forward as well. ASCO Daily News: Excellent. Dr. Rocque, let's focus on health equity and access. I'd like to ask you about the session on eliminating barriers to clinical trial access. The presenters of this session shared strategies to directly address inclusion and diversity in cancer care. Can you tell us about approaches that caught your attention? Dr. Gabrielle Rocque: Absolutely. So, this was a really great session talking about clinical trial access and barriers, and particularly as it relates to health equity. And so, in Abstract 74, Dr. Joe Unger presented a really interesting conceptual model that highlighted that the barriers to clinical trial access are not necessarily always at the patient level, but they are at the system level, the provider level. And this framework for considering how do we target in the future our ability to engage patients in clinical trials was really important, and I think was complemented well by the patient perspective from Rick Bangs, who's worked closely with SWOG, in thinking about how do patients view clinical trials and how can we better engage them. And I think folding together these different experiences and models to develop future interventions. I also thought the Abstract 75 looking at survival in the real-world analysis was noteworthy. And in particular, the ability to consider patients who are typically excluded from clinical trials based on their laboratory criteria and potentially having something like chronic kidney disease, and how little data there is on those patients who actually, in this study, had different outcomes after chemotherapy for breast cancer. I think when you think about clinical trial access and inclusion, I also think you need to think about how we collect our data and how we consider race and other social determinants of health. So, there were a few other abstracts that, although not in this session, I think were incredibly important for us to consider. The first is Abstract 78 by Ms. Niveditta Ramkumar that talked about the association between rurality and race and surgical treatment and outcomes for non-metastatic colon cancer. And so, she talked a bit about the intersectionality between race and rurality, and I think brings up an important topic that we need to think about these constructs, not only as individual constructs but how they impact each other as we consider analysis in the future. And also Abstract 80 by Dr. Kekoa Taparra, which was a really interesting abstract that talked about the disaggregation of Pacific Islanders in major Asian subpopulations to reveal hidden cancer disparities. So, in this abstract, he discussed how we often lump together different populations, potentially because of small numbers, who really may have very different experiences and characteristics. And I think challenges us to move the field forward by identifying populations in groups that are, in fact, very similar to each other and not just pulling this together. And I think that will have an impact on how we view engaging patients in clinical trials, as well as reporting those clinical trial results that allows our providers to understand how the trial results fit for the patient that is sitting in their clinic for whom they're making their decisions. ASCO Daily News: Indeed. Dr. Wheeler, is there anything that you'd like to add on the issue of access to clinical trials? Dr. Stephanie Wheeler: So, there was an abstract that particularly sparked my attention, [Abstract] 79 presented by Dr. Jenny Xiang about the VA Connecticut Cancer Experience, where universal pre-screening and using computer algorithms to identify patients who might be eligible for clinical trials was used. And I think that this is an important approach that can help us rely less on the assumptions and the biases that exist in clinical care practice about whether a patient may or may not participate in a clinical trial, and instead use the vast amounts of information that we know about them in their electronic health record to try to preemptively identify them and approach them. We know that when patients are asked and invited to be part of trials, they are much more likely to say yes than people assume. And this could be a more unbiased way of assessing that eligibility, and then proactively identifying people, ideally, with a trial navigator. I think that would enable us to potentially overcome some of the barriers that exist and that are, frankly, institutionally biased in many cases. ASCO Daily News: Thank you, Dr. Wheeler. Dr. Rocque, the [ASCO Quality Care] Symposium featured an excellent keynote address by Dr. Ben Corn of Hebrew University of Jerusalem (“Integrating Hope – Real Hope! – Into Clinical Oncology”) and a wonderful lecture by Dr. John Cox, who was honored with the Joseph V. Simone award for advancing quality cancer care (“Reshaping Practice: Necessary Trouble”). Can you share some highlights from their talks? Dr. Gabrielle Rocque: Definitely. So, the keynote address by Dr. Ben Corn was perfectly timed for this meeting. I think everyone has had a difficult past 2 years with the pandemic. And his message of the importance of hope really struck a chord with me and many of the attendees, and how this is something that we can strategically work to improve, and that hope is something we can modify and train for. And so, I'm really excited to both hear this lecture and then also see what's to come in the future in this domain of hope-related research. Another session that I would like to highlight as well is Dr. Cox's talk after receiving the Joe Simone Achievement Award. And his lecture highlighted that change is coming. And he emphasized the importance of changing payment structures to be able to improve the quality of care that patients receive and to be able to leverage those changes for infrastructure that allows us to enable our health system to have a more patient-centered approach with many of the types of interventions that we've been talking about here today. So, I think both of those sessions are really must-watch sessions that I would like to highlight today. ASCO Daily News: Excellent. Well, the [ASCO Quality Care] Symposium also heard some compelling patient perspectives. Dr. Wheeler, can you share some of these messages with us? Dr. Stephanie Wheeler: One of the most powerful sessions in the entire meeting was the very first one, which was focused on the metavivor experience (“The Patient Voice: “Metavivors” and Long-Term Survivorship Care”). And I think because part of the intention of the planning committee was to proactively feature patients' voices at this meeting, this particular session was almost entirely comprised of patients and survivors. And living with advanced disease, as we know now, is very different than it was in the past. And we know that patients living with incurable disease may sometimes go on to live 15, 20, 25 years. And their needs are quite different than patients who have early-stage cancer. And so, this session was impactful because it represented a range of experiences. We heard from a caregiver. We heard from a young woman who's living with stage four melanoma, Dr. Tarlise Townsend (“An AYA Perspective”). And one of the things that I took away from this session in particular was that our approaches in the way that we talk to metavivors has to be fundamentally different, that they want providers to be truthful, they want providers to acknowledge the uncertainty and prognosis and the sometimes complex and rapidly changing regimens that may be available for them in terms of dealing with their disease. But they don't want to be condescended to, they don't want to feel like there's information that is being withheld. One of the things that Dr. Townsend shared that was very powerful was that she talked about how her providers, in many cases, outlined an optimistic future for her and would give her maybe unfair expectations about what the future might hold and think about it in terms of the outlier effect. But that's not the case for many people with her condition. And so, she talked about having to do her own death work--and that's her term--and how much time she spent really trying to understand for herself what the future looked like. And it just resonated so much with me. And everybody on this panel had similar stories to share about their experiences. And it reminded me that at the end of the day, we're all human. None of us deal with uncertainty well. None of us deal with death well, or the prospect of death. But the best that we can do in these situations is to be open and honest and straightforward and recognize the fear and the hope and all of that being intermingled, and really respect the person's autonomy and the person's experience and their ability to make plans for themselves going forward. ASCO Daily News: Thank you, Dr. Wheeler. We will have links to these important patient perspectives in the transcript of this episode, as well as the other abstracts discussed today. Dr. Rocque and Dr. Wheeler, thank you very much for sharing these important highlights from the 2021 ASCO Quality Care Symposium. Dr. Stephanie Wheeler: Thank you for having us. Dr. Gabrielle Rocque: Thank you so much. ASCO Daily News: And thank you to our listeners for your time today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclosures: Dr. Gabrielle Rocque: Consulting or Advisory Role: Pfizer, Flatiron Research Funding: Carevive Systems, Genentech, Pfizer Travel, Accommodations, Expenses: Carevive (an immediate family member) Dr. Stephanie Wheeler: Research Funding (institution): Pfizer Foundation Travel, Accommodations, Expenses: Pfizer Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.    

Dr. Scout and Dr. Charles Kamen discuss the findings of a key survey by the National LGBT Cancer Network of LGBTQI cancer survivors and strategies to improve cancer care for sexual and gender minority patients and survivors. Dr. Scout is the executive director of the National LGBT Cancer Network. Dr. Kamen is a clinical psychologist, assistant professor in the Department of Surgery at the University of Rochester Medical Center, and assistant director for community outreach and engagement at the Wilmot Cancer Institute.   Transcript ASCO Daily News: Welcome to the ASCO Daily News podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. The National LGBT Cancer Network has released the findings of a key survey of LGBTQI cancer survivors about their cancer treatment experience. To discuss the survey's findings and strategies to improve care for sexual and gender minority patients, I'm joined by Dr. Scout, executive director of the National LGBT Cancer Network, and Dr. Charles Kamen, a clinical psychologist and assistant professor in the Department of Surgery at the University of Rochester Medical Center and assistant director for Community Outreach and Engagement at the Wilmot Cancer Institute. Dr. Kamen also leads the University of Rochester's health equity research for the NCI Community Oncology Research Program. My guests report no conflicts of interest relating to our discussion today. Their full disclosures and those relating to all episodes of the podcast are available on our transcripts at asco.org/podcasts. Dr. Scout and Dr. Kamen, welcome to the ASCO Daily News podcast. Dr. Scout: Thanks. We're really happy to be here. Dr. Charles Kamen: Thanks so much for having us. ASCO Daily News: Dr. Scout, the survey captured the experience of over 2,700 individuals. And I think it's important to let our listeners know that approximately 100,000 LGBTQI people are diagnosed with cancer in the United States every year. So although the survey represents just a fraction of this total patient population, these data are important and shed light on the many challenges facing these patients and survivors from diverse communities across the country. What are the major themes that emerged from these data? And can you give us some specific examples from the survey. Dr. Scout: Yeah, absolutely. And first of all, I just want to say I'm happy that ASCO is paying attention to this. It's something that we're really proud of having done with the help of about 150 community partners. So, it was really kind of a community-wide effort. And we're really delighted to have this much information about a topic that is so important. The main takeaway is--we have really kind of four overarching themes we really think about a lot related to the survey. One of them--and this is nice, because we did a survey about 11 years ago, and this is actually pretty different--and that's that many people were able to report that they were able to get welcoming care. So, that we can't directly compare. But we do think that that is kind of a sign of changing times, a sign of the fact that a lot of providers really are trying to do a better job in this arena. But, unfortunately, there's a few big caveats to that. One is that people often had to go through a much longer journey to get to welcoming care, whether that be physical distance or trying several doctors, different things like that. No one needs that when they're under the duress of a cancer diagnosis. Second of all, if you were any underserved or underrepresented population within the queer communities, like trans or a person of color, your chance of getting that welcome care, of course, dropped. And then the second big theme is that our families, our chosen families, not only are they a real source of resilience for us, but our support teams are different, usually, than general population support teams. It might be an ex, a best friend, and one cousin kind of thing. But if they're really our chosen family, we need to do a better job of having hospitals acknowledge and recognize and treat them as the people who are our key support teams. Not as much work is being done on that as we'd really like to think is the case. The third big theme is that a lot of us, we're really looking for tailored resources about all sorts of things, including cancer prevention strategies, even right down to we wanted LGBTQ-tailored resources for physical-activity strategies. And we were almost uniformly unable to get those resources. So there is, especially these days, in a time when you can tailor things down to lots of different subpopulations, we still have a pretty big miss related to what's happening with the queer population on that. And then the fourth thing--and this we can only really kind of hypothesize--but people were talking about some kind of brutal statements that their doctors were making to them, people who were being told they have cancer in a very rough way, things like that. And we don't wonder if this could be the phenomena of the microaggressions emerging through standard care. And that's something that concerns us and, I think, something to watch. Dr. Charles Kamen: It's amazing to me, Scout, that the themes from this survey are so similar to the previous survey that you conducted back in, what was that, 2011? Dr. Scout: Yeah. Dr. Charles Kamen: So it's been 10 years, and still the same themes are coming up for this population. Dr. Scout: It is the case. Geraldine, you may not even know this, but Charlie is the other human who is the best expert in the world on what our last survey was, because he worked with us to do a bunch of publications off of it. And yeah, I would say it's distressing. We might have had, potentially, a reduction in some of the phenomena. But we had action steps, coming out of the last survey, that we've been training and we've been going around talking to everybody about for obviously over a decade now. And unfortunately the news is still the same. ASCO Daily News: Well, Dr. Scout, I'd like to follow up on a point you made about the importance of welcoming care. Certainly the environment in which people receive care can have a significant impact on their experience. Only 12% of respondents in the survey felt that they had received care in a welcoming environment where they saw, for example, a rainbow flag, they saw affirmative messages, and so forth. This is a very significant takeaway for oncologists in community practice and elsewhere. So, Dr. Scout, do you have any tips for providers about how to make LGBTQI individuals feel welcome, in a safe space, whether they are face to face with their oncologist, or getting blood work done, or even a biopsy? Dr. Scout: Yeah, we absolutely do. If you think about it, there is a history of bias and discrimination against this set of communities. And unfortunately, right now, if you're not doing something to distinguish yourself from that history, we can't tell. You know, we can't tell that you're not part of the problem. So, what we say and all the cultural competency trainers say to providers would be, show us. Do something. Don't just think to yourself, well, I support Pride or something like that. But, do something so we can tell as the patients. So, there's a whole bunch of strategies that are very simple. Put the Rainbow Pride flag up in your office. Partner with a local queer organization to do some outreach. Make sure that you have tailored materials on your website. If I go on your website and search the word, bisexual, and find nothing, not even a non-discrimination statement, then how in the world am I supposed to understand that I might potentially be welcomed there? And in addition, one of the ways you can do it in a regular, routine, everyday interaction, people often ask, well, what about if I'm [doing this]--work on the systems at your organization, work on the media, work on what's in your waiting room, but then what do you do in that face-to-face interaction? Simplest thing is--it's a beautiful new thing--introduce yourself with your pronouns. So just say, hi, my name is Scout. My pronouns are he/him. So, I'd like to get to know you. If you can tell me your name and your pronouns. And go from there. It doesn't say that you're queer, it simply says that you acknowledge one aspect of the difficulties experienced by the queer communities and that you're open and trying to be welcoming so that people, if they have unexpected pronouns or even if they have expected pronouns, they still get that little bit of a message that you're welcoming. ASCO Daily News: Dr. Kamen, do you have any thoughts on approaches that oncologists should be taking? And do you have a sense that these tips are being heard? Dr. Charles Kamen: I think that extra level to everything that  Scout said, which I 100% agree with, is don't put the rainbow sticker on the door unless your staff are competent to treat LGBTQ patients. So, before you have the visible sign of being affirming and welcoming, make sure that you're doing some training of the staff. Make it mandatory if you can. And think about how you are identifying and reaching out to your LGBTQI patients in your practice so that their identities are acknowledged and that they're referred to appropriate services after their cancer care ends or even during their cancer care. Dr. Scout: You know, I will also just say, related to that--and I completely agree--lots of providers, when you refer anybody out to another provider, if you're welcoming, you want to refer them to a welcoming provider. And unfortunately the strategy for figuring that out right now is still usually a provider calling another provider and figuring out how welcoming they are, and then doing follow-up with the patient. So, kind of even above and beyond that, remember, especially as an oncologist, your patient is going to now have to experience a bunch of other people. What have you done to make sure that you're able to refer them to welcoming providers instead of just having your own office be welcoming? Dr. Charles Kamen: And how are you working within the community to be sure that about resources that are outside the walls of your institution, but that may be very LGBTQ-affirming? You may not have an LGBTQI support group in your cancer center, but there may be a great one in town that you could refer patients to. So, I think it is both acknowledging visibly that you are an ally, but putting action to that by looking around for resources to send people to. Dr. Scout: And if not, we have new national ones you can refer people. Dr. Charles Kamen: Yes. ASCO Daily News: Thank you both for making those great points. Dr. Kamen, you've done [so] much research on the experience of LGBTQI individuals in cancer care and have stressed the need for research that is specific to the needs of this population. Can you tell us about the role that identity plays among LGBTQI individuals in determining levels of distress? Dr. Charles Kamen: If I can dip back into history for just one second, people probably know that, up until 1973, homosexuality was listed by the American Psychiatric Association as a mental illness. And there's still, to this day, discussion around diagnoses like, quote unquote, "transsexualism," or gender identity disorder, or gender dysphoria as sources of psychological distress. So, there's been a longstanding recognition that LGBTQI identities carry with them a burden of distress. But it wasn't really until the early 2000s that researchers like Vickie Mays or Susan Cochran and Ilan Meyer started to recognize that issue wasn't the LGBTQI identities themselves, the issue was living in a society where LGBTQI individuals were exposed to constant stigma and discrimination. And this led to the development of the Minority Stress Model which many researchers still use today as a way to understand why LGBTQI people experience higher levels of distress and have higher rates of diagnoses like anxiety and depression than heterosexual and cisgender people. I won't go into an incredible description of Minority Stress, but just the basic premise of it is that LGBTQI individuals walk around the world every day with a stigmatized identity. They could be directly exposed to discrimination as a result of this identity, or they could see people in their community being discriminated against, or anticipate discrimination going into a new environment or situation. So, all of this can cause chronic underlying stress. There was some very cool pioneering work by Mark Hatzenbuehler and his team that showed that really it's the process of ruminating about these experiences that causes physiologic changes like inflammation. And that has a cascade effect, downstream, on having high rates of distress among LGBTQI people. And I think, in cancer, we can see this whole process playing out very clearly. We were talking before about the survey that was done in 2011 that I worked on with Scout. And I always talk about this one participant in that study who said, "My oncologist knew about me."--she was a lesbian patient--"My oncologist knew I was a lesbian." But every time I had to encounter a new person, whether for an X-ray or a blood draw, I had all the anxiety of that cancer procedure plus the possibility of homophobia and having to watch out for myself. Cancer is stressful for everybody. But then, if you have to constantly negotiate whether and how to come out to your providers, you have to brace yourself for discrimination if you do come out. And then, if you don't come out, you have to worry, well, does my provider really know me as a human being if they don't know this important part of myself? All of that can exponentially magnify the stress that LGBTQ people with cancer experience. And so that's really, I think, at least the theoretical framework for understanding these rates of distress. Dr. Scout: Hey, Charlie, you may not know this, but did I ever tell you that I was diagnosed as a homosexual in 1984? Dr. Charles Kamen: I wasn't sure how much to go into it. Yeah, I mean, it was still floating around in the Diagnostic and Statistical Manual until 1987, I believe, you could be diagnosed. Dr. Scout: Also, just really bring home what Charlie is talking about on the other end of it, you know, here I am, the executive director of the National LGBT Cancer Network. And trust me, my partner had to push me to go to the dermatologist to get something checked out, which ultimately was cancer. You know, it's fully treatable. But there's this real difference between those of us who are kind of like, stiffly this is what we should do, you know? And then when you face the fact of standing naked in front of a provider who you think could be cruel to you, it's a very daunting possibility. So, there's a million ways you can find something else that's going to be your priority that day other than take care of your health needs. Dr. Charles Kamen: Absolutely. And it also causes people to not want to disclose. But then we had another person from the survey who said there's a part of the cancer experience that never gets shared with providers if they don't know who you really are as an LGBTQI person. So, it's really a catch-22. ASCO Daily News: So, what is the absolute best practice, in your opinion, to get an assessment of sexual orientation or gender identity that doesn't rely on the patient's disclosure? How should this ideally be done? You've discussed it before, earlier, in our conversation. But is there a best practice that our listeners can take away with them today? Dr. Charles Kamen: I mean, just based on the minority stress model, it's definitely incumbent on the practices to assess Sexual Orientation and Gender Identity, or SOGI, in a way that's comfortable and affirming for patients. And most of the time, as we're saying, right now, the onus is on the patient to disclose, which is super unfair. Usually it happens organically. A patient will come in, an LGBT patient will come up with the same-sex partner, and introduce their partner to the provider. And then it is just kind of known that they are a sexual minority person, or based on a med list, or pronouns, or name on an insurance card, a transgender status is known. But sometimes it doesn't happen that way. It doesn't happen organically. And there's a real breakdown in communication then. And beyond that, a patient's dealing with a million things at the beginning of a cancer journey anyway. So, having them be the ones to figure out how to talk about this is very unfair. I think the best research we have on this topic is from the EQUALITY study which was done a couple of years ago now by researchers from Harvard and Johns Hopkins. And it focused specifically on the emergency medicine context. But they surveyed a ton of people and providers and found that the overwhelming majority of patients were willing to disclose SOGI, but that they preferred to do it non-verbally, so through a form or a survey or a patient portal, and not verbally, face to face with a provider. That felt less stigmatizing and intense to the respondents in this survey. Dr. Scout: The other key piece about that is that an overwhelming number of providers thought that they shouldn't know that information because it was too invasive. So, we really need to close that gap. Dr. Charles Kamen: I forget the exact percentages, but it was something like-- Dr. Scout: It was 90% were willing to disclose, but 80% of providers thought that they shouldn't know. Dr. Charles Kamen: Yes, yes, thought that patients would not disclose. And there was some variation by the LGBTQI identity, with heterosexual patients being a little lower, like 84%, and lesbian respondents, like 98% of them were like, yes, ask us, we want to tell you. So, there is that mismatch. And I think the takeaway message, though, is patients are comfortable providing this data if it's asked of them in a respectful and affirming way. Dr. Scout: And I was going to say, just kind of bringing this down to just real-life experience, I had an experience at a health center recently that I think really is--it was certainly the best practice I'd ever had. And that's that I walked into a waiting room. And in the waiting room, I could see three different cues that they were LGBTQ welcoming. There was a big banner sign saying, "We welcome everybody." There was some stuff up about their Pride activities even though it wasn't Pride Month. And then there was a rainbow sticker on the window or something like that. By the time I saw those three signs, the fourth thing was they asked me my sexual orientation and gender identity on my intake form. And by then I was like, absolutely, no question, I'm absolutely going to give it. And I will say they even had a fifth thing. I then went through the patient--and it was like a dental procedure--I went through the procedure, and afterwards something happened that literally made my hair stand up on my neck because I realized how far away we are from this. Someone called me and said, "I'm from the health center. This is Thundermist"--our local federally-qualified health center. "I saw that you marked down that you were trans. I just wanted to welcome you. I'm the trans outreach coordinator. And I wanted to talk to you about some different trans support activities that we have going on across the health center, like swim night, game night, yoga night, things like that." So, I mean, really it made the hair stand up on my head. I'm like, wow, I'm not just tolerated here, I'm valued. And it was the first time I think that I had ever considered or thought that in a health interaction in my life. Dr. Charles Kamen: That's incredible. And I think that's the real next step we have to take as organizations, health care organizations, and as a society. If we're going to collect these data, why? What is it being used for? Dr. Scout: What are we giving back? Yeah. Dr. Charles Kamen: Yeah. How are we referring people to things like a trans yoga night? Make sure there's action behind collecting the data. Dr. Scout: But even before that, before we collect, are we showing them it's safe before we ask them to disclose? So, basically are we going out on a little bit of--not even a limb, first, but are we putting our cards on the table before we ask them to put their cards on the table? Dr. Charles Kamen: Yeah, don't go in cold. Let them know it's a safe place to have this disclosure. Dr. Scout: Yes. Dr. Charles Kamen: I will add in, too, we in the ASCO Sexual and Gender Minority Task Force recently conducted a survey with the support of ASCO's Center for Research and Assessment. And we found, by polling over 200 ASCO members, that the two main factors that predicted whether a practice would collect SOGI data was leadership support, which makes sense--if the top is saying, this is important to do, we need to collect SOGI data, it's going to happen across multiple levels of the institution--but also having resources. And I think that's resources both for collecting the data itself, like IT resources or even knowing what questions to ask, but also resources like Scout's saying, to have banners and stickers and training and activities and support. All of that together makes the practice able to do this in a holistic and affirming way. Dr. Scout: You know, I will say, with the IT support, though, everybody has it in their software package these days. It's just a question of flipping the switch. There's built-in, pre-baked questions. They're not the best in the universe, but they're perfectly functional. So, I hope people realize that that's already there. Dr. Charles Kamen: Yeah. As of 2018, every electronic medical record has to, by federal law, have a SOGI data collection element within it. And then I think the resource may as much be knowing how to do it as the time and effort to turn those modules on. ASCO Daily News: Absolutely. So, here's a scenario. We have an LGBTQI individual who is receiving cancer care. And that person comes to the appointment with their caregiver. How should the clinician acknowledge the relationship of a patient or survivor and their partner? This is a very important aspect of care. Dr. Scout, what are your thoughts on this? Dr. Scout: Well, I presume this isn't the only set of people you're going to see where it may not be husband or wife. The concept of husband and wife have been expanding these days. So, I hope that the oncologist is asking who the person is who's with them. Is this your primary support person? Is this your partner? I just want to make sure, because, of course, having the right support and the best support is going to be important to you doing the best job getting through this whole health event. So, I would hope that the oncologist is introducing themself with their own pronouns, again, and then asking who all the people at the table are and how they relate to the patient. Because I think we know by now that all those other people are really going to be providing them with a lot of health care support in all those hours when the oncologist is not in front of that patient. Dr. Charles Kamen: I agree with that. And I think there are lots of examples of this process not going well, the question not being asked, and then the caregiver not being acknowledged for the relationship they have to the patient. And the real problem there is you don't get to offer the caregiver resources then. And a lot of LGBTQ patients and their caregivers report that the caregivers experience as much stress or more stress than the patient does. So, by getting at this relationship, by asking a simple question like, "Who do we have with us today?" you can then refer that caregiver to a support group or resources as needed. ASCO Daily News: Of course. I'd like to focus on mental health for a moment. Mental health is a huge concern. And 70% of respondents of the National LGBT Cancer Network survey reported that they never received resources related to mental health developed for LGBTQI individuals. I'd like to read a quote from one respondent, who wrote, "With respect to mental health in particular, it seems that, locally, there are no criteria for what constitutes LGBTQI care. Mental health providers state that they are, quote unquote, 'friendly,' and have no means of describing what that means. Some are not at all aware of their own biases and subtle homophobia." Dr. Scout, what is your reaction to this statement? Dr. Scout: I think it's all too true. I've had a lot of challenges with the mental health system myself, as has probably most of the people that I know. So, it's yet again an area where I think the fix is not that complicated. I hope, by now, mental health providers understand [that] they do not see a homogeneous group of people. And I think, especially these days, since most people are going to the internet for their resources, this really begs the question of, you know, we don't have to wait for the National LGBT Cancer Network to create a bunch of resources. Because trust me, we're not that well funded. But if anybody makes a resource, send it to us. We'll put it on our resource library. And it can be available for anybody around the country. So, this really is going to take a village of providers to fix some of these issues. I'm not going to ask any one provider or provider group to fix all of them. But if everybody can do a little something, we'll pull all those together and make it available to everybody else. And that will really help build a basis of information. Also, just FYI, in cultural competency, there's a bunch of standards about to be released related to cultural competency. And we do provide trainings, as do other organizations. So, as with all of these things, take some steps. Inaction is hurting us. ASCO Daily News: Dr. Kamen, do you have any thoughts on this? Dr. Charles Kamen: Definitely. I agree with everything that Scout just said. And I think the one maybe silver lining to living through the COVID-19 pandemic has been that we are way more facile now at navigating telehealth services than we were pre-pandemic. I know, in our cancer center, our psycho-oncology service has had more business during the pandemic than before because they're offering virtual visits to patients. Even if an LGBTQI patient doesn't find a provider within their health care facility that they feel is competent or welcoming, you can go on the internet, as Scout is saying, and you can find really excellent queer-focused and affirming therapists that you can see virtually. So, that's, I guess, one benefit and one thing I hope that we continue to innovate on as we move through 2021. Dr. Scout: The one thing I would say about that is a lot of that's being threatened by these licensing issues. Because a lot of that is only being provided under licensing exceptions for COVID-19. Likewise our support groups are living under a licensing exception for COVID-19. So, there has been increasing pressure at a lot of places. I was literally just talking to the White House about it 2 days ago--no, that would be over the weekend--right before the weekend, about how telehealth really is a huge concern for our communities. And continuing these exemptions for all rare and underserved and discriminated-against populations and rural populations that just don't have a big provider base around them, is going to be really, really critical. So, I hope that there's going to be action on this telehealth front to make these licensing exceptions stick and not just be a little bright light that goes away once we've decided COVID-19's done. Dr. Charles Kamen: Absolutely agree. And I think that's at the federal level and the state level too. We need advocacy to make sure that these telehealth expansions remain in practice long term. ASCO Daily News: Dr. Kamen, you cited some interesting research earlier in the conversation. Is there any other research that is specific to the needs of the LGBTQI population that you'd like the oncology community to be aware of? Dr. Charles Kamen: Oh my gosh, I feel like there's so much good stuff going on now. And it's an amazing change from 2011, when I first started working with Scout on that survey, which was really the only survey of its type anywhere. Now there is more of a groundswell of interest and effort around LGBTQI cancer care. I'll just highlight three of the projects that are happening with members of the ASCO SGM Task Force. So, I've been working with the Fenway Institute in Boston, which has pioneered a lot of LGBTQI cultural competency training. And we're trying to bring that training and SOGI data collection elements to community oncology. And that's part of the NCI Community Oncology Research Program research base that I work with. So, that's one thing. Mandi Chapman, another member of the ASCO SGM Task Force, has a beautiful, very comprehensive training that's called the Together Equitable Accessible Meaningful, or TEAM, training. And she's tailored this to SGM-specific care and is testing it with multiple cohorts of health care providers. I think there'll be a publication coming out about that sooner rather than later so keep an eye out for that. And also I believe she is recruiting additional cohorts. So, keep an eye out for that as well. And then Ash Alpert, another member of the ASCO SGM Task Force, got a Young investigator Award from the Conquer Cancer, [the ASCO Foundation]. And they are developing patient-centered, non-stigmatizing gender identity data collection methods that can be implemented across oncology settings. And they're also looking at connections between violence and cancer risk for the transgender population. Really, I think this work is incredibly timely. Because people may know or may not know that right now the National Academies of Sciences, Engineering, and Medicine, they're working on a consensus document that's really trying to summarize how best to collect SOGI data across settings. So, Dr. Alpert's work to get a trans-community perspective on this topic is super critical. Of course, I would be remiss if I didn't mention the National LGBT Cancer Network and their training that they're doing as well, which I believe is still in existence and can be accessed, though Scout, you can correct me if I'm wrong on that. Dr. Scout: We're actually also doing a partnership right now, with Society for Gynecologic Oncology, to convert it to an online enduring training so it can scale wider. And we actually expect that to be debuting at the beginning of next year. Dr. Charles Kamen: Yeah, it's so great that there are so many of these efforts happening, because it means that multiple groups can access the training through different channels. And we can end up, hopefully, with a much better pipeline of LGBTQI-competent and trained providers. The last thing I'll mention is that the ASCO SGM Task Force had done that survey to look at the factors that predict SOGI data collection. And we're now doing a phase II follow-up where we're going to be doing qualitative, in-depth interviews and focus groups with member organizations to try to understand what the factors are on the ground that predict people collecting SOGI or not. So, we'll definitely be looking for organizations to participate in that study, probably in the next couple of months. Dr. Scout: And I would say you're hearing us talk a lot about data collection because that really is the biggest next horizon related to advancements in SOGI care. Because just to be clear, we can't tell you what our cancer rates are because we don't have any data in any of the registries because that's all abstracted from health records. So, until we get these questions asked as you go into a health care environment, we won't be able to tell you what our disproportionate COVID-19 impact is, we won't be able to tell you our cancer rates. And of course, without a lot of that hard data, we also can't even apply for more research or do interventions to try and fix it. So, that's why one of the things we really try and encourage providers to look at is when are you going be able to flip that switch and actually do that data collection. If you're really committed to being inclusive for our population, that's a key step. ASCO Daily News: Absolutely. Well, we will share a link to the National LGBT Cancer Network survey in the transcript of this episode, along with all of the other research and resources that you discussed today. Thank you so much, Dr. Kamen and Dr. Scout, for being on the podcast today and shining a spotlight on a very important topic in cancer care. Thanks so much. Dr. Scout: Absolutely. Thank you. ASCO Daily News: And thank you to our listeners for your time today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclosures: Dr. Charles Kamen: None disclosed  Dr. Scout Research Funding (institution): Bristol Myers Squibb Disclaimer:  The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Get .1 ASHA CEU hereEpisode SummaryHey school-based SLP's, Want to learn how to do more for your students struggling with language, using less time and less direct instruction from just you? Well then, shimmy on over to this week's episode, where Dr. Trina Spencer and Dr. Doug Peterson return to share some “friggin awesome” intervention-focused follow-up to their previous talks on MTSS and dynamic assessment (DA). If you've listened to this duo on prior episodes, you know they are dynamos, dedicated to natural and holistic language approaches that help students across the board. In this chapter,, Trina and Doug walk us through their 10 principles to multi-tiered language intervention, providing the simple but highly effective tools we need to foster oral, written, and academic language skills that really stick for our students. This one got me thinking, made me cringe a bit at my past practices, and inspired me to further harness the power of narrative to make big impacts on language proficiency for students at risk and those with known disabilities. As with any good SLP Nerdcast story, you'll learn something, you'll laugh, and you'll meet a strange frog with shapeshifting powers. Well, maybe that last part isn't like every Nerdcast story, but who doesn't love a good plot twist in the series!You can learn more about Trina and Doug here.Summary Written by Tanna Neufeld, MS, CCC-SLP, Contributing EditorLearning OutcomesDescribe the characteristics of effective language instruction. Explain how academic language can be addressed through narrative intervention.Explain how response to intervention within multi-tiered systems of support reduces the number of evaluations SLPs will need to do.ReferencesKelley, E., & Spencer, T. D. (2021). Feasible and Effective Language Intervention Strategies that Accelerate Students' Academic Achievement. Seminars in Speech and Language, 42(02), 101-116. doi:10.1055/s-0041-1723839Kirby, M. S., Spencer, T. D., & Chen, Y. I. (2021). Oral Narrative Instruction Improves Kindergarten Writing. Reading & Writing Quarterly, 1-18. doi:10.1080/10573569.2021.1879696Nelson, B. S., Petersen, D. B., & Rai, A. (2021). The effects of a multi-tiered system of language support on oral narrative language, writing, and reading comprehension in India. Language and Education, 1-21. doi:10.1080/09500782.2021.1898633Petersen, D. B., Mesquita, M. W., Spencer, T. D., & Waldron, J. (2020). Examining the Effects of Multitiered Oral Narrative Language Instruction on Reading Comprehension and Writing. Topics in Language Disorders, 40(4). doi:10.1097/tld.0000000000000227Spencer, T. D., & Petersen, D. B. (2018). Bridging Oral and Written Language: An Oral Narrative Language Intervention Study With Writing Outcomes. Language, Speech, and Hearing Services in Schools, 49(3), 569-581. doi:10.1044/2018_lshss-17-0030Spencer, T. D., Moran, M., Thompson, M. S., Petersen, D. B., & Restrepo, M. A. (2020). Early Efficacy of Multitiered Dual-Language Instruction: Promoting Preschoolers' Spanish and English Oral Language. AERA Open, 6(1), 233285841989788. doi:10.1177/2332858419897886Weddle, S. A., Spencer, T. D., Kajian, M., & Petersen, D. B. (2016). An Examination of a Multitiered System of Language Support for Culturally and Linguistically Diverse Preschoolers: Implications for Early and Accurate Identification. School Psychology Review, 45(1), 109-133. doi:10.17105/spr45-1.109-132Online ResourcesShift to Workload Model Shows Enhanced Learning, Reduced ReferralsTrina's ToolboxLanguage Dynamics GroupA big THANK YOU to our Corporate Sponsor, Med Travelers for the financial support to make this course possible! To learn more about Med Travelers visit https://www.medtravelers.com/ Disclosures:Dr. Petersen financial disclosures: Dr. Petersen is a co-authors of the Story Champs curriculum and PEARL dynamic assessment. They receive royalties from the sales of those items. Dr. Petersen has no financial relationships to disclose.Dr. Spencer financial disclosures: Dr. Spencer is a co-authors of the Story Champs curriculum and PEARL dynamic assessment. They receive royalties from the sales of those items. Dr. Spencer has no financial relationships to disclose.Kate Grandbois financial disclosures: Kate is the owner / founder of Grandbois Therapy + Consulting, LLC and co-founder of SLP Nerdcast. Kate Grandbois non-financial disclosures: Kate is a member of ASHA, SIG 12, and serves on the AAC Advisory Group for Massachusetts Advocates for Children. She is also a member of the Berkshire Association for Behavior Analysis and Therapy (BABAT), MassABA, the Association for Behavior Analysis International (ABAI) and the corresponding Speech Pathology and Applied Behavior Analysis SIG. Amy Wonkka financial disclosures: Amy is an employee of a public school system and co-founder for SLP Nerdcast. Amy Wonkka non-financial disclosures: Amy is a member of ASHA, SIG 12, and serves on the AAC Advisory Group for Massachusetts Advocates for Children. Time Ordered Agenda:10 minutes: Introduction, Disclaimers and Disclosures20 minutes: Descriptions of the characteristics of effective language instruction and MTSS fundamentals 15 minutes: Descriptions of how academic language can be addressed through narrative intervention 10 minutes: Descriptions of how response to intervention within multi-tiered systems of support reduces the number of evaluations SLPs will need to do. 5 minutes: Summary and Closing__SLP Nerdcast is a podcast for busy SLPs and teachers who need ASHA continuing education credits, CMHs, or professional development. We do the reading so you don't have to! Leave us a review if you feel so inclined!We love hearing from our listeners. Email us at info@slpnerdcast.com anytime! You can find our complaint policy here. You can also:Follow us on instagramFollow us on facebookWe are thrilled to be listed in the Top 25 SLP Podcasts!Thank you FeedSpot!

Get .1 ASHA CEU hereEpisode Summary:You're a rockstar SLP. You read the research. You eat, drink, sleep EBP- but something still feels like it's missing... Reading the literature makes your brain hurt. You feel like you just can't make this research-based practice stuff work. It's like you're jumping into the research-to-practice gap without a parachute. Enter implementation science-the game changer, your parachute. Ok, you're probably like “Implementation what now? Never heard of it!” I'm with you. SIt tight, it will all make sense soon... In this episode, Dr. Cathy Bringer and Dr. Natalie Douglas uncover the what and why of implementation science and how it stands to change the EBP face of your day-to-day SLP life. There's ah-ha moments, pats on the back, validation, and more as this down-to earth research duo acknowledge the short-comings of the traditional research model and promise a brighter research-to-practice future- tearing down hierarchies, building up clinicians, and using implementation science to study clinical practices that will actually work in the “real world”.Learn more about Cathy and Natalie here.Learning Outcomes1. Describe a brief history of implementation science and its recent intersection with SLP 2. Distinguish between the traditional research pipeline and alternative research designs focused on implementation 3. List barriers and facilitators to SLPs engaging in clinical research ReferencesDouglas, N. F., Campbell, W. N., & Hinckley, J. J. (2015). Implementation Science: Buzzword or Game Changer? Journal of Speech, Language, and Hearing Research, 58(6). https://doi.org/10.1044/2015_jslhr-l-15-0302 Fixsen, D. L., Naoom, S. F., Blase, K. A., Friedman, R. M. & Wallace, F. (2005). Implementation Research: A Synthesis of the Literature. Tampa, FL: University of South Florida, Louis de la Parte Florida Mental Health Institute, The National Implementation Research Network (FMHI Publication #231)Olswang, L. B., & Prelock, P. A. (2015). Bridging the Gap Between Research and Practice: Implementation Science. Journal of Speech, Language, and Hearing Research, 58(6). https://doi.org/10.1044/2015_jslhr-l-14-0305 Disclosures:Dr. Natalie Douglas financial disclosures: Dr. Douglas receives a salary from Central Michigan University and The Informed SLP; She also receives book royalties from Plural Publishing and has research funding from The American Speech-Language-Hearing Foundation. Dr. Douglas has no non-financial relationships to disclose.Dr. Cathy Binger financial disclosures: Dr. Binger is employed by the University of New Mexico. Dr. Binger non-financial disclosures: Dr. Binger is a member of ASHA and special interest group (SIG) 12. Kate Grandbois financial disclosures: Kate is the owner / founder of Grandbois Therapy + Consulting, LLC and co-founder of SLP Nerdcast. Kate Grandbois non-financial disclosures: Kate is a member of ASHA, SIG 12, and serves on the AAC Advisory Group for Massachusetts Advocates for Children. She is also a member of the Berkshire Association for Behavior Analysis and Therapy (BABAT), MassABA, the Association for Behavior Analysis International (ABAI) and the corresponding Speech Pathology and Applied Behavior Analysis SIG. Amy Wonkka financial disclosures: Amy is an employee of a public school system and co-founder for SLP Nerdcast. Amy Wonkka non-financial disclosures: Amy is a member of ASHA, SIG 12, and serves on the AAC Advisory Group for Massachusetts Advocates for Children.Time Ordered Agenda:10 minutes: Introduction, Disclaimers and Disclosures20 minutes: Descriptions of implementation science and its recent intersection with SLP15 minutes: Descriptions of the traditional research pipeline and alternative research designs focused on implementation 10 minutes: Descriptions of barriers and facilitators to SLPs engaging in clinical research 5 minutes: Summary and ClosingDisclaimerThe contents of this episode are not meant to replace clinical advice. SLP Nerdcast, its hosts and guests do not represent or endorse specific products or procedures mentioned during our episodes unless otherwise stated. We are NOT PhDs, but we do research our material. We do our best to provide a thorough review and fair representation of each topic that we tackle. That being said, it is always likely that there is an article we've missed, or another perspective that isn't shared. If you have something to add to the conversation, please email us! Wed love to hear from you!__SLP Nerdcast is a podcast for busy SLPs and teachers who need ASHA continuing education credits, CMHs, or professional development. We do the reading so you don't have to! Leave us a review if you feel so inclined!We love hearing from our listeners. Email us at info@slpnerdcast.com anytime! You can find our complaint policy here. You can also:Follow us on instagramFollow us on facebookWe are thrilled to be listed in the Top 25 SLP Podcasts!Thank you FeedSpot!

Transcript: Dr. John Sweetenham: Hello, I'm John Sweetenham, Associate Director of Clinical Affairs at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center, and the guest host of ASCO Daily News Podcast today. I'm joined by my friend and colleague, Dr. Derek Raghavan, President of the Levine Cancer Institute to discuss a new study that he and his group published in JCO Oncology Practice outlining a novel approach adopted by his institution to address financial toxicity caused by the rising costs of cancer care. Dr. Raghavan is going to tell us about the creation of a Financial Toxicity Tumor Board, which shows promise as a potential solution to significantly ease the financial burden of cancer treatment on patients and their families (DOI: 10.1200/OP.21.00124). Dr. Raghavan's full disclosures are available on our show notes, and disclosures relating to all episodes of the podcast can be found in our transcripts at asco.org/podcasts. Derek, it's always a pleasure to be speaking with you again on the podcast. Dr. Derek Raghavan: Hi, John. It's a pleasure to have time with you again. Dr. John Sweetenham: You know, I've had an opportunity to read the publication in JCO Oncology Practice, and it really is fascinating and a very interesting new approach. We know from many studies that financial toxicity is among the most rapidly growing adverse effects of cancer treatments. And patients report financial distress is a major hurdle to the quality of life. And its association with worse outcomes is now very well documented. At the Levine Cancer Institute, as your paper describes, you created a Financial Toxicity Tumor Board, which you abbreviate to FTTB, to address this problem. And I wonder if you'd be able to describe a little bit about this tumor board, and perhaps in particular which components of this you feel are really a new approach to addressing the issue of financial toxicity. Dr. Derek Raghavan: Thanks, John. Yeah. I mean, I guess it's important just to define what we're talking about because there are still people, particularly clinicians, who don't really understand the concept. So, I think it was probably Jonas de Souza, among others, from Mark Ratain's group, who were early in both identifying this as an issue and studying it. And so, the concept of financial toxicity is really pretty simple. And that is that people are struggling to pay their bills and the bills are going up. With the way the pharmaceutical industry is able to set prices ad libitum, the fact that there's a lot of lobbying that goes on in Washington, and elsewhere, the prices that people have to pay can be really quite extreme. People that are insured are, perhaps in this domain, particularly at risk because if you have, for instance, a good insurance policy with a 10% copay, and think about the cost of maybe half a million or a million dollars a course of targeted therapies or for CAR T treatment, or whatever, 10% of $500,000 is an awful lot of money for someone to come up with unexpectedly. So, the whole idea of financial toxicity is something that has emerged with the rising costs, and more particularly, the rising prices of health care. I think the other thing that that's important is while we are seeing this reported more, and you know this from your experience, as to why, patients really protect their financial status almost more than anything else. They don't like to admit that they're struggling financially. And there will be people who are mortgaging the house, but who don't share with the medical team that they've run out of money, that the health insurance plan isn't working. And so, they're really making choices that are very tough. If you have no income and no insurance, I'm not implying that it isn't a problem. There are people who will still have bills to pay and have to make choices between buying food and buying their drugs. And in your practice and in mine, we both know that sometimes patients select in favor of food, which makes perfect sense, because they can't afford food and drugs. So, the whole concept of the Financial Toxicity Tumor Board came from understanding that. At the Levine Cancer Institute, we have a big commitment to outreach and underserved populations that the team that's led by my colleague, Melissa Wheeler, last year had 68,000 people that they saw at outreach. And that included a lot of uninsured or underinsured people. And they were bringing back to me stories of the difficulties these folks were having in terms of why they weren't seeking medical care. Given that we are the safety net in this part of North Carolina, that's particularly troubling. And then the final thing that I'd say is with respect to underreporting, we here use a system called Tridiuum, which is an electronic system that asks patients about their quality of life. And one of the cases--one of the questions that is asked is, are you having difficulty paying your bills? And when we compare what we've learned at the FTTB, the Financial Toxicity Tumor Board, with the answers on Tridiuum, it's quite clear that patients, while they'll talk about nausea, and vomiting, and pain, and things like that--depression--they will often say, no, I'm not having trouble financially. They'll answer to the question, no, I'm not having trouble. But we actually find out they are. And the final point I'd make--and I suspect that because you and I went through medical school a couple of decades ago, we were both taught that it's rather inappropriate to discuss something as unpleasant as money with patients because it will make them feel that we're judging them or that we're withholding treatment. As a consequence of that, physicians have been trained really not to discuss the costs of care. And that becomes a pretty big deal when you're actually going to have a patient that might give up little Johnny's college education for a new treatment. I mean, it might be worth it if it's going to cure them. It might be worth it if it's going to give them a 10-year survival. But if you're talking phase I study, or a drug in the third or fourth line, which might give 2 or 3 months of extra survival, giving up little Johnny's education might be a bad trade-off. And so, the whole concept of the FTTB was to get us to do things to help patients, but also to get a physicians and the advanced practice nurses and the whole team to be focusing a little more carefully on the whole issue of this problem for patients. So, coming back to your core question, we developed a tumor board, much like breast cancer tumor board, or GI, or whatever, that is multidisciplinary. It has all the service chiefs at our institute, several of the physicians from different domains, the nurse navigators--we have about 40, 45--our financial counselors, the people in the billing office--so administrators. I'm at present, at these finance people. We get together and identify the worst of the problems. We have a couple of our finance people and a couple of our financial counselors who triaged the cases. If it's something simple--so Mr. Smith is age 70 and hasn't managed to get Medicare for some reason. That's not an FTTB problem. That just gets handled by the financial counselor or the navigator. But if it's one of the big problems that we found, like people who don't have insurance, people who are getting impediments from the payers, issues that relate to coding and billing, problems of precertification, that's the time when the FTTB becomes involved. Dr. John Sweetenham: That's great. Thanks. And I think that the point you make about these are issues which affect the insured as well as the uninsured are really important. And interesting that you have--it sounds like you have a pretty systematic way in which you can identify and engage those patients who might be embarrassed or reluctant to disclose that they have some level of financial distress. Dr. Derek Raghavan: Yes. That's correct, John. We have some signs posted. All of our staff are trained to raise the issue in as nonjudgmental and as engaging and passionate as they can. Interestingly, it's often the front-line staff at the front desk or the nurse navigators that get the information. A proportion of our patients will actually just ask for help and see a financial counselor. But the whole group has been trained to be as empathetic as possible and to create a scenario where it's kind of put to the patient that we understand this is not on you. This is the way health care is today. There are gaps that relate to how we pay for it. So, let us try to help you. And I think for that reason, patients are much more comfortable to address the issues once they understand how this works. Dr. John Sweetenham: Right. Could you say just a little bit more and expand on how the patient assistance program kind of fits into this model? And then as a follow-on question to that, could you tell us a little bit about what the cost savings for your patients have been and how many patients have been impacted by the tumor board so far? Dr. Derek Raghavan: Sure. Well, the process, as I explained, is multidisciplinary with a whole bunch of different people. We've folded all the bits together. So, we have social workers and financial counselors who can access philanthropic support for the people where we simply can't figure out an answer. And so, in that context, that'll be copay assistance or other philanthropic things. We actually measured this in 2020 and 2019. And so, in 2019, we gave out about $1.4--a little bit more--million to about a little over 1,200 patients. In 2020, it was about $1.39 million, and it was about 1,000 patients we helped. In terms of saving out-of-pocket expenses, I was surprised when we actually measured it and looked at it. So, in 2019, we helped nearly 600 patients. And we saved them out of pocket expenses of $55 million. Dr. John Sweetenham: Wow. Dr. Derek Raghavan: In 2020, it was 749 patients. And there, to my surprise, it was $60.7 million. So, this is not chump change. This is really big sums of money. We did an analysis and we reported this in JCO OP and found that 29% of the patients just were dealing with lack of insurance or under insurance. Oftentimes, a policy that had fine print that said, while you're well, we'll cover you. And when you're sick, we won't. So, we had to deal with that. There were payer impediments. And you and I both--I know we've chatted about this over the years. There are wonderful payers and health insurance companies and there are some that are pretty tough. They all pay their insurance executives seven or eight-figure sums--and claim to be struggling. But the payer impediments will relate to changing their rules, having fine print that doesn't cover the rules. One month, you'll have to get--so for example, at one point, we discovered that they were turning down rituxan for diffuse large cell lymphomas. And there was one word in the diffuse large cell that was missing from what the doctors might have been writing. And so, they were denying payment for that and sending bills to patients. There will be coding or billing complexities. That's, again, at about 20% of the cases we've seen. The toughest one is only a small proportion at the moment because we've worked on it, but it's variable--and that's precertification. And the problem there is the companies change their rules for who needs it and who doesn't. For example, in North Carolina, Medicare recently required precertification for chemotherapy that didn't require it previously. And they set a start date and suddenly we had to cancel a bunch of patients for that date because the website to allow precertification didn't open until the day began. And so, we had to just defer by 24 hours chemotherapy so that we could get the patients precertified to avoid them getting bills. And then I have to say--I mean, 20% of our problems have been inadequate internal processes. And that means if we'd done things better internally, we could have avoided problems. And so that brings in the way we approach management of denials. We've become very proactive. So, I now have a team of pharmacy techs who, for example, chemotherapy will go through the rules for each health plan for the individual patient to make sure that we're actually doing the precertification correctly as of the day of treatment because the rules may have changed. So that's pretty much how it works. We've got pharm techs who work the cases in advance. We often spend an awful lot of time talking to insurance companies. As you know, they can make it very difficult to get to the right point with the recent changes with white bagging and brown bagging where they're deflecting and deferring referrals of treatment to their own pharmacy companies, that will often not be patently obvious till we have a patient here ready to go, and we suddenly discover that they want us to get the drug from a specialty pharmacy that's their special one. So, all of this requires an awful lot of advanced planning. Now I think if government took a little more interest in the way the insurance companies work, it would make life easier--but they don't. And so, we have used this strategy of Financial Toxicity Tumor Boards to move this forward. And I will say that one of the very useful things it's done, it's sort of like ripping a Band-Aid off. It's created a scenario where we are now able to educate our physicians about things that they simply didn't know existed in terms of problems of reimbursement insurance and so on. Dr. John Sweetenham: Right. And so, the process and the success that you've described with this tumor board is really pretty remarkable. I'm quite struck by the fact that this requires a lot of resource-- particularly, human resource--and a lot of organization to make it work. So, we often talk about whether a new initiative is something that's scalable. Do you think that this FTTB model is something that's scalable down, if you see what I mean, so that it could be successful in relatively small practices as it has been in a large system such as the one that you operate? Dr. Derek Raghavan: Yeah, John, I think that's a really good question. So, if you're thinking about scalability, if you're thinking about a place like the Simmons Cancer Center at UT Southwestern led by Carlos Arteaga and yourself, I'm sure that you could do something similar. It's a big center, it's a national referral center, it's NCI designated, and you've got reasonable support and philanthropy. So, you could do this, if you wanted to, easily.   If you then scale it down to a private practice or an office oncology practice, I think the answer is, you can do much of it. You might not be able to do everything that we do. But it's certainly reasonable that if you have, say, 30 patients coming up over 5 days for chemotherapy, your chemotherapy nurses can be rostered to actually do some of the work that we do in terms of checking insurance situations and so on. Many of the smaller practices worked predominantly with two or three health insurance companies, so therefore there are less sets of rules. I think the other thing is a lot of the stuff is repetitive. So, I gave you an example of rituxan and lymphoma. So, if you've got people focusing on those who can send a note around the practice to say, moving forward, if you want to prescribe rituxan, is the phrase that needs to be there to describe the type of diffuse large cell lymphoma you're addressing. So, I think it is scalable. It's more a question of changing attitudes and accepting that medicine has changed, people are struggling to pay their bills. And physicians--particularly in an oncology space--can actually spend a little time going through the cost of care with patients, thinking about the alternatives. We use biosimilars a lot. We're very careful to use biosimilars where the evidence really supports the fact that they are an equivalent product. Occasionally, we struggle with that because the insurance companies obviously are doing deals with some of the biosimilar companies, and we may be at short notice discovering that we need to prescribe biosimilar number two rather than number three when we thought number three was the best drug. That becomes an ethical issue. And then I think you just have to look at the quality of the data and decide whether it's reasonable or not. Some of the biosimilars, I think, are ones where we're not sure that they're equivalent and then we do not use them. Dr. John Sweetenham: So, we've talked a lot at a system level and the kind of global problem that we all face now with the financial toxicities. But ultimately, this is an issue for individual patients. And with the system that you've put in place, the ultimate beneficiary of this, of course, is the patient. And I just wondered if you may be able to share perhaps one example or a couple of examples of patients whose stories kind of exemplify how helpful this can be. Dr. Derek Raghavan: Yeah. Yeah. I think in the story that we told; we described a patient where there was confusion on the explanation of benefits that was provided to the patient. This was a person with--who'd had adjuvant chemotherapy following surgical treatment of pancreatic cancer and then suddenly got a whole bunch of bills because it was noted that one of the drugs--just one of the drugs in the chemotherapy regimen--required specific precertification, which actually was not clearly seen in most of the documentation that was available. So, in that situation, our financial counselor actually talked to the company and was able to make things better. In the situation of patients with malignant lymphoma heading to bone marrow transplantation, that's been one where various companies have used denials as a mechanism of creating leverage for contracting. There, what we've done is generally approach doctor-to-doctor to the physicians who work for the companies. As a general rule--and I don't think this is an overstatement--I think it's easier if you talk doctor-to-doctor to a company that will employ an oncologist or a retired oncologist. Unfortunately, sometimes it'll be a retired surgeon or an internist who's punching well above his or her weight. And that's a little bit more tricky. Frankly, I in my own practice in the past have used politicians. When we get finally to a dead end, I will provide a letter that describes what we've done, give it to the patient, and say I suggest you go and see your local congressman or senator. It's amazing how quickly payers respond to a phone call from a politician. And that's because there's an awful lot of lobbying that goes on in Washington. The companies certainly don't want to bring attention on themselves. But I think, generally, it can be quite a good partnership if the physicians are doing their part and thinking about the bang for their buck. In other words, are they providing treatment that's going to make a difference? They make sure they're following the rules, and that requires proactive management. Develop a good relationship--the companies certainly respond to a group that are trying to provide cost-effective care. Dr. John Sweetenham: Thanks. And just one last question before we wind up. And that is, I think this wasn't the primary motivator for setting up your tumor board, but what do you think the impact of this kind of approach--if we were all to adopt this more formalized approach, what do you think might be the impact that it would have on cancer care disparities? Dr. Derek Raghavan: I think it can help. I think the biggest problem--and John, you'll roll your eyes because you've heard me say it before--I have a problem with analysis paralysis. So many people working in the NCI-designated network and beyond it love to do studies of underserved populations. And my thought is, why don't you start trying to problem solve and tweak it as you go along? And so, I think what this sort of approach does is it makes physicians and advanced practice nurses, and oncology pharmacists think more about the issue of the cost versus outcome. It allows us to help patients to deal with the problem. And because we're trying to bring all the costs down, it really goes to the value proposition. As I think you know, we have electronically accessible pathways that are evidence-based, but certainly looking at the costs of care for equi-active and equitoxic drugs is a big piece of that. That's why we sometimes use biosimilars. So, it will generally bring the costs and prices down while also trying to help reduce the out-of-pocket costs for our patients and make us more value-orientated in terms of the whole product. And the other thing I think is really important is if we can do it in oncology, then the cardiovascular people, and the neuroscience people, and so on can equally be thinking along these lines. Dr. John Sweetenham: Yeah, absolutely. I agree with you. And I'd have to say, I really appreciate having an opportunity to talk with you about this. When I read the article, I immediately fired it off to our leadership team here to take a look at because I think there is much to learn and commend this particular article and the application of this type of tumor board to everyone who's listening. It's a really very, very interesting and novel approach to what is clearly going to become an increasing problem for our patients with cancer. So, in conclusion, I would just like to say, thanks again, Derek, for sharing some time with us and sharing your insights into the tumor board. Dr. Derek Raghavan: John, it's always a pleasure to chat with you, and especially to be interviewed by, and I've enjoyed this discussion. I hope it's been helpful to your audience. Dr. John Sweetenham: I'd also like to thank our listeners for joining us today.  You'll find a link to Dr. Raghavan's study in the transcript of this episode. And finally, if you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts. Thanks, and goodbye.   Disclosures: Dr. John Sweetenham: None disclosed. Dr. Derek Raghavan: Consulting or Advisory Role: Gerson Lehrman Group, Caris Life Sciences Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

ASCO Daily News: Welcome to the ASCO Daily News podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. The American Cancer Society reports that at least 42% of newly diagnosed cancers in the United States, excluding non-melanoma skin cancer, are potentially avoidable because they are attributable to lifestyle factors. Today we will discuss strategies and resources to help the oncology community focus on health promotion as a key component of cancer risk reduction as well as in survivorship care. Joining me for this discussion are Dr. Amy Comander, the director of breast oncology and cancer survivorship at the MGH Cancer Center in Waltham and at Newton-Wellesley Hospital, and Dr. Poorvi Desai, a hematologist-oncologist at Comprehensive Hematology Oncology in Tampa Bay, Florida. Both Dr. Comander and Dr. Desai are board certified in lifestyle medicine. My guests report no conflicts of interest relating to our topic today. And their full disclosures and those relating to all episodes of the podcast are available on our transcripts at asco.org/podcasts. Dr. Comander and Dr. Desai, it's great to have you on the podcast today. Dr. Amy Comander: Thank you so much for the invitation. Dr. Poorvi Desai: Thank you, it's really great to be here. ASCO Daily News: Dr. Comander and Dr. Desai, you recently co-wrote an interesting editorial featured in the ASCO Daily News that raises concerns about newly diagnosed cancers in the United States that are potentially avoidable because they are attributable to lifestyle factors. You also note that as the population of cancer survivors in the U.S. continues to grow, risk factors for cancer development are becoming more prevalent. So the obesity epidemic in the United States is a huge concern. This is just one risk factor for cancer. Dr. Comander, can you tell us about this and other risk factors and why oncologists should be addressing these risk factors sooner rather than later? Dr. Amy Comander: As you clearly stated, there's increasing prevalence of obesity in this country. And this has troubling consequences in terms of cancer risk and outcomes for specific types of cancer. Interestingly, just this week, we learned data from the annual report to the nation on the status of cancer that, overall, cancer death rates in the United States are declining, especially for lung cancer and melanoma. And this is amazing. And that is due to the incredible advances in treatments that we've witnessed over these past few years. But interestingly, for prostate cancer, colorectal cancer, and female breast cancers, death rates continue to increase or these declines have slowed or even leveled off. And in terms of understanding why that may be the case, it seems that lifestyle factors, such as obesity, lack of physical activity, [and] increased alcohol use, may be risk factors for why we are seeing these results. And therefore, further research will certainly need to be done in this area, but attention to these factors is very important. ASCO Daily News: Well, Dr. Desai, I'd like to ask you about your interest in lifestyle medicine. I understand you became interested in lifestyle medicine during your fellowship training. Can you tell us about this? Dr. Poorvi Desai: Yes, I recently just graduated from my hem-onc fellowship at USF and Moffitt Cancer Center. And I was really impressed during my fellowship looking into all of the data very particularly when it comes to every single different type of cancer. But one thing I thought was lacking was just the overall picture of lifestyle factors, and especially modifiable risk factors, when it comes to pre-survivorship along with things that patients can do during active treatment and in the survivorship phase. And I think that there are structures that are starting to appear to help guide us with more evidence-based data. And so I became very interested, as I had an attending in my internal medicine residency who was a part of lifestyle medicine. And through the American College of Lifestyle Medicine, I met several people around the country who had been working with organizations such as AICR, as well as the World Health Organization, [and] American Cancer Society. And there was a very big push on these lifestyle factors to look at them in a way that is actually studied through evidence and actual guidelines that I was never really taught about throughout my fellowship. So I made it a point to kind of self-teach a lot of this. But I definitely think that there's a role moving forward in bringing this to not just fellowship education but just all of oncology care, whether it's medical oncology, surgical, radiation, but just any oncology care team. ASCO Daily News: Well, you make a really great point. Evidence-based guidelines do exist to help facilitate lifestyle modification in cancer care, but there are barriers to health promotion in cancer care. Dr. Comander, what are the major barriers? Dr. Amy Comander: That's an excellent question because we know this is an important issue. And actually, it was an issue studied recently by ASCO. Dr. Ligibel and colleagues published a paper in 2013 that was a survey of oncologists and their understanding of obesity and other lifestyle factors and how they address these issues in clinic (DOI: 10.14694/EdBook_AM.2013.33.52).  And I think we can all say that our colleagues are well aware that obesity and lifestyle factors play an important role in cancer outcome. But in terms of the practical steps of how to address these issues with our patients, how to get our patients to lose weight, how to get our patient to exercise, how to help our patient cut back on alcohol use--those are just some examples--there really are limitations. And in that paper, they really outlined some of the reasons for that. Some of it is lack of education, as Dr. Desai just noted. She sought out teachings and lifestyle medicine as part of her fellowship training. She had to go elsewhere to look for that because it really wasn't part of the standard curriculum. So a lack of education, lack of resources. I'm fortunate to work in a cancer center with excellent oncology colleagues with expertise in nutrition, exercise, et cetera. But we know, in the rest of the country, not every doctor has access to these resources. And the third reason is really lack of clinician time. Our visits are very focused. And often the priority, of course, is discussing the patient's treatment, how is--I'm a breast cancer doctor. How is my patient doing on her endocrine therapy? What kind of side effects is she experiencing? How can I ensure she's complying with her medication? So there really isn't a lot of time to address these issues in a visit. So these are all factors we need to work on. ASCO Daily News: Well, how about solutions? How tough is it to convince patients who are grappling with the physical and emotional toll of cancer treatment to prioritize their nutrition and exercise? Dr. Desai, what do you think are the next steps? What would you say to oncologists who really do need to pay more attention to this? Dr. Poorvi Desai: So I think that one of the biggest things to take out of our article is that oncologists don't need to carry the burden of doing this by themselves. I think that while it does take a lot of resources, which is a big constraint, especially financially, I do think that there is a lot of worth in building a care team that's dedicated towards this. Or if that's not possible, then seeking out community, local, or national resources and kind of bringing together any other structure that's already in place and having a good referral to those areas, so that patients do understand that it is important to continue physical activity and working on nutrition. And I definitely think that it's something that patients feel they can have some control over. I think a lot of oncologists don't feel qualified to talk about these things because they are not very well taught in our education. And so I think then a lot of patients in this realm of lifestyle feel on their own in trying to figure out what's good for them, what's not good for them. There's a lot of misinformation online and unsolicited advice that can be given to our patients. There's a lot of fear around foods and what the right type of activity is. And I think that the more evidence-based information that we have to provide to our patients, we can be more confident in making these suggestions. And again, we don't--as oncologists, we don't need to be the ones who are actually doing all the counseling, doing all of this, making sure that they have their exercise prescriptions or whatever it may be, but at least acknowledging that this should be a part of the care team and seeking out resources that the care team can then take over. So that in conjunction with active treatment or in conjunction with survivorship care, this then becomes something that patients feel they have some kind of control over. And I also think that it's important that we don't over-promise and under-deliver as well. I think that it's important to show patients that these are things that are as important as their active treatment to pay attention to, but also as oncologists start becoming more comfortable with the idea of risk reduction and having the information to back up our claims that lifestyle is of the utmost important in cancer. ASCO Daily News: Absolutely. Dr. Comander, do you have any thoughts on this? Is it more difficult to do what Dr. Desai has described in a community practice than where you are in a larger institution? Dr. Amy Comander: I think Dr. Desai answered that question beautifully. I will add that, as an oncologist, what we say makes such an impression on our patients. Often our patients are recording what we say, or they have a family member with them writing down everything we say. So if we just tell our patient, it's really important for you to exercise--and that might just mean a 10 minute walk each day or walking to the mailbox to get the mail, starting with something very basic in terms of exercise counseling--can make a big difference. And so I think just the fact that, as Dr. Desai just stated, a doctor acknowledging that exercise has a role, nutrition has a role, stress management has a role, I think just that simple act has a big impact on our patients. And it's very important. ASCO Daily News: Indeed. Well, patients and survivors often grapple with depression, anxiety, fear of recurrence, financial issues, and more. Sleep disorders and insomnia can interfere with adherence to a nutrition plan or an exercise regime. Are there helpful tools available, or what are the helpful tools available to oncology practices to help them address these issues with their patients? Dr. Amy Comander: I think that's a really important question. We know that distress screening is actually incorporated into each visit. And that's recommended through the NCCN guidelines really to assess these issues you just inquired about--coping skills, anxiety, depression, financial issues, et cetera. So certainly, it's very important to ask our patients about these issues and refer them to appropriate colleagues, whether that's a mental health provider or social worker, to help address these concerns. I will also acknowledge ASCO has a number of great resources to help guide patients to. The website Cancer.Net has many resources that help patients find perhaps something in the community that could help them address these specific concerns. Dr. Desai, I'm interested in your comments as well. Dr. Poorvi Desai: I absolutely agree with you. I think that the NCCN is doing a really great job in compiling a comprehensive set of resources in their survivorship guidelines. There is that distress assessment thermometer that we had addressed in our article. We definitely understand that these psychosocial evaluations are pretty much of utmost importance. There's a lot of anxiety and distress that comes with a cancer diagnosis. And we know that it lasts. It has an impact that's lifelong. And so definitely one of the big pillars of lifestyle medicine is stress and social connectivity. And so we definitely are an advocate for having mental health professionals as a part of the care team and looking at mental and physical well-being going hand-in-hand. And I think one of the biggest things to understand is that we have to meet our patients where they are. And so we don't want to advocate for anybody saying, OK, now you have to exercise five times a day strenuously, and you have to eat perfectly, and all of these things that can be extremely overwhelming. And so I think that there are great guidelines. And I think the NCCN Survivorship Panel has put together a good amount of resources for us to show patients how to work on mindfulness strategies and sort of systematically work them through a very difficult diagnosis in order to slowly, but surely, result in those healthy lifestyle changes. I like to tell my patients that it's a marathon, not a sprint. Any progress is good progress. You don't have to be perfect. And I think that's definitely something that we should be mindful of when we talk about changing lifestyle behaviors. ASCO Daily News: Right. Dr. Comander, do you think there is a role for increased collaboration between oncology providers and primary care providers in the context of cancer survivorship, for example? Survivors might see their oncologists every few months, every 6 months, every year, but who is monitoring the hypertension, the weight gain? Who should own that responsibility, or is it a collaboration? Dr. Amy Comander: That's a great question. And as you stated at the beginning, thankfully due to advances in treatment and screening, the number of cancer survivors in this country is increasing greatly each year. And therefore, it is very important that we have a strong collaboration with our primary care colleagues in terms of providing excellent care for our patients following completion of primary treatment. So in my practice, it definitely is a collaboration. I'm fortunate to work with so many wonderful primary care physicians [and] we work together in terms of monitoring our patients' blood pressure, risk for cardiovascular disease, risk for diabetes and other chronic diseases, and certainly when it comes to other lifestyle interventions, such as weight management, management of substance abuse, et cetera. So that collaboration is really key. And I see primary care providers already playing a huge role in survivorship care. And I think that will continue to grow in time to come. ASCO Daily News: Well, as you said, the number of cancer survivors continues to grow. It's projected to increase to 22 million in the United States by 2030. So do you think the focus on lifestyle medicine will increase in the future? Let's start with Dr. Desai. Dr. Poorvi Desai: Yeah, I think that this has to become one of the major things that we regard. I think that most oncologists are very aware that our treatments are--they have long term consequences. We had mentioned in our article that there are two major themes to look at when it comes to survivorship care. One is infection-related mortality. But the other big one, which is what we focused on, was lifestyle--cardiovascular disease, cerebrovascular disease, accelerated aging with telomere shortening and metabolic changes that happen after cancer diagnosis and the treatments that patients receive. So a lot of what we are subjecting our patients to is truly aging in nature. And we have evidence to suggest that we can work on these lifestyle modifications as the forefront way to really help them overcome the fact that we have given them radiation to their chest or cardiotoxic medications, or whatever it may be. And that when they are overweight or obese, this can then further accelerate that process of metabolic aging. I think one of the things that's really important to talk about is assessing metabolic health. And so not just looking at their BMI, but how does their BMI actually break down into metabolic patterns? How much of this is bone density or muscle weight? We put patients a lot on hormonal treatments, which can then affect their fracture risk moving forward. And I think that we are very well aware of that. And so these are the things that should really be assessed because, like we've mentioned, one of the biggest reasons for, I guess, moving forward with the number of cancer survivors that we're going to have, a lot of it--the focus needs to shift, basically, to long term chronic disease management, in which lifestyle really does play a huge role. ASCO Daily News: Absolutely. Dr. Comander, is there anything else that you'd like to share before we wrap up the podcast today? I certainly do think your article pointed out the importance of using evidence-based guidelines to strive for the best possible outcomes for survivors and patients to prevent newly diagnosed cancers. Dr. Amy Comander: Yes, I think, as summarized in our article, we did provide resources that can help our colleagues address these concerns with our patients, since, again, some of us have not been educated about these topics during our medical training. So in addition to the excellent resources provided by ASCO, I would really refer our listeners to the AICR website, American Institute for Cancer Research. In addition, the American Cancer Society is playing a role in helping provide further education about the role of nutrition and physical activity in cancer survivorship. So the American Cancer Society is a great resource, as is the American College of Sports Medicine when it comes to exercise recommendations. And on their website, they have some great graphics that really illustrate what the recommendations are for exercise and what the benefits are for cancer survivors as well. And finally, we referred to the NCCN during this podcast. And of course, their guidelines are excellent and address these lifestyle behaviors as well. So I would just highlight those resources for our listeners in case they want to get more information. ASCO Daily News: Absolutely, some great resources there. Well, thank you, Dr. Comander and Dr. Desai, very much for sharing your valuable insight with us today on the ASCO Daily News podcast. Our listeners will find a link to your article in our show notes. Thank you very much. Dr. Amy Comander: Thank you so much for the invitation. Dr. Poorvi Desai: Thank you so much. ASCO Daily News: And thank you to our listeners for your time today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclosures: Dr. Amy Comander: Consulting or Advisory Role: Advance Medical, Applied Genetic Technologies Corporation, Beam Therapeutics, Biogen, Inc., Blue Cross Blue Shield Association, CRICO Harvard Risk Management Foundation, Editas Medicine, GenSight Biologics, Harvard University, infiniteMD, RBC Investments, Sanofi SA, Vedere 1, WAVE Life Sciences Dr. Poorvi Desai: None disclosed.  Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

In recent years, the Food and Drug Administration approved several new treatments specifically for the treatment of multiple sclerosis and neuromyelitis optica spectrum disorder. But what about neuroimmunological conditions that do not have FDA approved options and require off-label use of immunomodulatory medications -- conditions like neurosarcoidosis, neuro-Behcet's, or central nervous system involvement of systemic rheumatologic conditions? There is often a lack of rigorous evidence to guide treatment of these conditions, leaving experts to rely on individual or institutional experience. Our guest on this episode is Dr. Jeffrey Gelfand, neuroimmunologist and Associate Professor of Neurology at UCSF. He specializes in treating patients with rare neuroinflammatory conditions, and he'll talk to us about the new drugs for NMO as well as off-label use of immunomodulatory therapies for a range of neurological conditions. Dr. Gelfand was interviewed by ANA producer Dr. Rohini Samudralwar. Series 2, Episode #9 Disclosures: Dr. Gelfand receives research support to UCSF for clinical trial from Rosch and Genetech; provides consulting to Biogen

Dr. Ben Corn, professor of Oncology at Hebrew University of Jerusalem Medical School, and deputy director of the Shaare Zedek Medical Center, discusses his current research with NRG Oncology and SWOG on the study of the science of hope, and it's role as a mediator in well-being and health care improvement. Dr. Corn is co-founder and CEO of the NGO, Life's Door, which teaches health professionals, patients and others strategies for hope, meaning and well-being throughout illness and at the end-of-life.   Transcript ASCO Daily News: Welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. Our guest today is Dr. Benjamin Corn, a professor of oncology at the Hebrew University of Jerusalem Medical School and deputy director of the Shaare Zedek Medical Center. Dr. Corn is the co-founder and chairman of the nonprofit organization Life's Door, which teaches health professionals, patients, and caregivers strategies for hope, meaning, and well-being throughout illness and at the end of life. Dr. Corn was honored with the 2021 ASCO Humanitarian Award and joins me to discuss his work, including his current research on the study of the science of hope and its role as a mediator in well-being and health care improvement. Dr. Corn's full disclosures are available in our show notes, and transcripts for all episodes are available at asco.org/podcasts. Dr. Corn, it's great to have you on the podcast. Dr. Benjamin Corn: It's a pleasure to be here, and thank you very much, Geraldine. ASCO Daily News: Dr. Corn, can you tell us about the experiences early on in your personal life and then your medical training that prompted your interest in helping patients find hope and meaning while navigating cancer treatment? Dr. Benjamin Corn: Sure. I think everyone has a story that sent them on their way for a career in medicine, which for many of us is not a job. It's not a career. It's a mission. My personal story had to do with losing a parent, my dad, at a very young age. He died of prostate cancer, left behind three young children and a lovely widow, who was my mom. And I was quite disappointed with the way the system tried to cope with the reality that was now forced upon us. There were no viable options for somebody with metastatic prostate cancer then. But yet, there was not a cognizance of some of the psychological trauma that we would all have in trying to navigate our daily lives. And I was very surprised also the way my dad's death was communicated to the family. And I've spoken about this in a variety of podcast settings and written a piece for the JCO narrative section about 10 years ago on that, some of what I found to be harshness, coldness of telling us that our dad was not going to make it and how the bad news was conveyed (PMID: 24733795). And so, with that, I was an 11-year-old child, and I very much was intent on curing this thing called prostate cancer to make sure other middle-aged men wouldn't suffer from it, and their families wouldn't have to pick up the pieces. And I went to medical school. I entered my residency in oncology at University of Pennsylvania, thinking that that was my destiny. And when I got to the wards, I was quite disillusioned because I saw a variety of scenarios that told me things hadn't changed drastically in 7 or 8 years since losing my dad and initiating my medical studies. I saw many cases of senior attending physicians, who were fantastic scientists, brilliant researchers, and yet didn't seem to pay enough attention to the subtleties of making sure that a family was whole, bringing in other resources. This was right before what I would call a palliative care revolution. We didn't have the Tamil paper, the Zimmermann paper, the Bakitas paper. And we didn't really know the value of early interventions with teams that included not only oncologists but also nurses and psychologists, chaplains, who could help navigate such a difficult period for patients and for the people in the concentric circles around those patients. So it was very important for me to begin to explore those issues. I never found it to be a conflict for pursuing an academic career that asks bread-and-butter questions about disease, areas of interest. I published a lot in gynecologic malignancy, in prostate cancer itself, and in central nervous system tumors. But by the same token, I thought it was very important to be looking at the psychosocial dynamics that are involved. And that's pretty much the genesis of how I got interested in this area. ASCO Daily News: Well, your work integrating hopefulness into cancer care has had an important impact even on communities beyond the medical setting. Can you tell us about this work, about the hope enhancement model, and how you've used this approach to train medical professionals, patients, and caregivers? Dr. Benjamin Corn: Well, first of all, I want to say that, in many ways, even though I've been blessed with having terrific education at outstanding institutions of higher learning, my greatest teachers have really been the patients, and I'll bet you most colleagues would say the same thing. And I noticed there was a subset of patients who were very intuitively aware of what was important to them, patients for whom the prognosis was very bleak and yet managed to maintain hopefulness. And I saw that the common thread for these patients was that, even though they couldn't be hopeful for cure, they could still find other goals, other objectives that they could pursue. And that sent me on a quest of sorts to see if anybody had formally tried teaching people how to become more hopeful. And with not too much effort, I found literature of Professor Rick Snyder from University of Kansas. It basically modeled this notion of hope theory. And without turning this into a lecture, very briefly, Snyder said that there are three conditions that will allow hopefulness to thrive. The first is defining a goal. And by that, he meant some kind of an objective that was not only plausible but also that could provide meaning in one's life. So it would be a good goal in hope theory if I said my goal is to win the lottery tomorrow because that's really not anything I can have an impact on, so it's not really statistically plausible. But likewise, if I took a goal that was just very mundane and didn't add that much purpose to my life, it would be out there, and I'd be interested in pursuing it. But I probably wouldn't have the same degree of motivation if I thought about something that, without too much effort, could really make my day or make the day of the people around me. So, the first thing was the goals that have these two criteria--plausibility and meaning. The second is a pathway to get to the goal. And when Snyder discusses pathways of thinking, he's supposedly speaking to a mature audience and saying none of us were born yesterday. We all realize that on almost every path that we travel on during our lifetimes, we see that there are obstacles. The question is, how do we manage and circumvent those obstacles, or how do we dance with those obstacles if, in fact, it's something very much within me, an obstacle such as anger, an obstacle such as jealousy? How do I deal with those particular factors? A hopeful person is a creative person, is a resourceful person, who finds a way to sally forth even when these obstacles are out there. So we have goals. We have pathways. And finally, the other secret sauce that I mentioned before is motivation. The word that Snyder used for motivation is called "agency." Agentic thinking, like almost an agent that might represent an NBA basketball player or a Hollywood movie star. That agent will do everything on behalf of his or her colleague so that they'll succeed. And so to the person who has an agentic way of seeing the world is going to be an activist, is going to want to set out on those trails, those pathways, to reach those goals. So those are the three components. And what we found is that--and this is based on some work that was done by one of Snyder's proteges, Dr. David Feldman, who's at Santa Clara University--one could actually construct workshops that are very palatable, that take less than 2 hours to conduct, in which a tool called hope mapping is used. Hope maps are basically dependent on those three components. So you can actually sit there in dyads, buddying up with people in this workshop, people who you know before the workshop, or people who you meet in the workshop, because there's a similarity, a selection for those who attend such workshops. People want to work together. And it's a wonderful energy, because let's say, as I said before, I have a goal, and I have a pathway. But there's a big, bad obstacle there, and I don't know how to get around it. What could be that my buddy in the workshop is going to say, "You know what, Ben? Here's a great way. You might not have thought about this. Why don't we contemplate creating a workaround?" And they're very, very instructive. And we've done some of these workshops now, both in Israel, where I practice, as you mentioned at the opening, and with colleagues at Johns Hopkins in Baltimore with really thought leaders in hopefulness--Tom Smith, who has for many years written the ASCO guidelines on palliative care, and Anna Ferguson, who is the coordinator of the hope enhancement program at Hopkins. And together, we've proven, especially in a population of women suffering from stage IV breast cancer, that we really can invest 2 hours or less and make them much more hopeful. Now, you mentioned in your question that some of this has an impact on communities beyond the medical setting, and that's exactly what's been happening. As the word has trickled out, especially during the COVID pandemic, we've been approached by a variety of communities on the international level--communities in London, communities in Athens, communities in South Africa, communities in the Pacific Rim--who are very interested in bringing together different strata within those communities, perhaps people who have recently become married or people who have recently become parents, who have a similar set of struggles, and to help us help them become more hopeful, especially when you add on to that a little something called COVID-19. So I'm an oncologist. I think there's tremendous upside for this in the setting of cancer care for patients and for the health care professionals who have the privilege of treating these patients. But the spillover phenomenon has really been marvelous to behold, especially during 2020. ASCO Daily News: Well, you're also collaborating with the National Cancer Institute groups of NRG Oncology and the Southwest Oncology Group to study the science of hope and its role as a mediator in well-being and health care improvement. Can you tell us about this research? Dr. Benjamin Corn: Sure. So in the context of NRG Oncology, there are two protocols. One is called CC003 (NCT02635009). That's a protocol for patients with small cell lung cancer. And another one is a protocol called BN005, which is a protocol for individuals with, I guess, what we want to call low-grade gliomas, to look at neuroanatomic loci that could constitute a source for hopefulness (NCT03180502). I'll just give you one example, which is from the small cell lung cancer study I mentioned before. So in years past, at least, it's been a standard of care to provide prophylactic cranial irradiation--that is, prevention with radiation--where there's a tumor, small cell lung cancer, that has a proclivity to spread to the brain. And so one of the hot areas that has emerged in radiation research over the last decade is hippocampal avoidance. It seems trivial, but it took us a while to understand how to protect concentric circles, such as, let's say, the spinal cord when treating the vertebral body or to protect the hippocampus when treating the whole brain. So in prophylactic cranial irradiation, we typically treat the whole brain. And a randomized trial was developed by NRG investigators, where the randomization was between prophylactic cranial irradiation itself to 25 Gray in 10 fractions versus that same regimen with hippocampal avoidance. Now, when I saw that study design, I actually put forward the idea that this could be a wonderful model to study the neuroanatomic correlative hopefulness because there are several candidate anatomic structures in the brain, which are thought to be associated with hopefulness. No one, by the way, is saying that the circuitry is so primitive that all of hopefulness resides in one structure. But if I had to say that there's a lead candidate that's been identified in the literature, it's exactly the hippocampus. So the proposal to the NRG committee and to the PI of the protocol, Dr. Vinai Gondi, and the head of the brain tumor committee, Dr. Minesh Mehta, was, could we very simply administer one of the validated scales for hopefulness that was built by Snyder. It has all of 12 questions. It takes about 5 minutes to complete. Give that to a patient at baseline, then have them randomly assigned to either prophylactic cranial irradiation of the whole brain or the same treatment wherein the hippocampus is protected. Re-challenge the patients 6 months after the irradiation is completed, and see if there is less of a decrement in hopefulness on these validated scales among the group that had the hippocampus protected. When you compare the hopefulness among the groups that didn't have the hippocampus protected, that would offer some interesting, at least circumstantial, evidence that the hippocampus is implicated in the hope pathways. And so this has been very interesting to NRG Oncology. We've enrolled now over 250 patients en route to 300 patients. We have very meticulous quality assurance, where the co-investigators sit down once a month and make sure that the hippocampus was properly contoured and protected. And in the other study, we're looking at particular dosimetric analyses in case someone thinks that 25 Gray might be, for instance, below the threshold of hippocampal tolerance. There, we'll look at a variety of doses to see where we might see the correlation with hippocampal toxicity and decrements in hopefulness. So those are two variations of ideas that are on burners in NRG Oncology. SWOG has taken a different tack. And here, I want to truly applaud SWOG leadership, the group chair of SWOG, Dr. Charles Blanke, as well as the leaders in the palliative care movement at SWOG, including Mark O'Rourke, Marie Bakitas, and Ishwaria Subbiah, who have said, "Look, we know that you've got some preliminary pilot data on the impact of a hope workshop for patients with cancer. Can we, first of all, look at this now among the SWOG investigators?" That had never been done before. In other words, we talk all the time about levels of burnout among health care providers who are treating a patient with cancer. It's very gratifying on the one hand, but it's very challenging on the other hand. It can even be demoralizing for some, and as you know, there are very high rates of burnout. So they've been very interested, first of all, in meticulously establishing levels of hopefulness at baseline and correlating that with levels of burnout among SWOG investigators. So by "investigators," I'm talking about physicians, nursing professionals, even patient advocates. And we have some data that were just recently published in JCO Oncology Practice (DOI: 10.1200/OP.20.00990). In addition, we've been very interested in offering now these hope enhancement workshops that I told you about before to the SWOG investigators. So in the month of May, we got together every Monday night--at least for me, it was Monday night at midnight, I have to say, which was about 5:00 PM Eastern time. And we did these 2-hour workshops every week for about a dozen SWOG investigators. And we actually have some data right now that we just submitted to the ASCO Quality Conference, showing the feedback we got from the SWOG investigators. And to me, the most encouraging part was that these investigators were so enamored of these techniques and found them to be so useful that they--almost all wanted to find ways to bring them into their own clinical environment to share them with their patients, wanted to learn how to become facilitators of such workshops to also help prophylax burnout and increase hopefulness among their colleagues. So SWOG has taken the tack of using this intervention to help providers. We're soon going to be trying to do it among the patients and roll it on to our protocols. And there, what we want to do is take meaty, challenging questions. Let's say the question of adherence, a situation where perhaps women who need endocrine therapy are somewhat--want to take the endocrine therapy but are somewhat reluctant to be adherent to the regimen because of all the hormonal side effects. So we want to see if we can use our workshop to align this value of a patient and this motivation with the patient to help them, in fact, become very adherent, because as I'm sure you know, upwards of 40% of these patients just don't want to take these therapies. So we're interested in using this for adherence. And we're also interested in using it as a tool for medical decision making. We give a lot of lip service to the idea of shared decision making between provider and patient, but most of us haven't really been trained in how to have a robust experience that helps me as a provider understanding what my patient wants. When I counsel patients with prostate cancer, it's almost impossible for me to do such a consultation in less than 90 minutes because there's such a range of options. And before I can really get to understanding which of those options might be most appropriate for a patient, I have to really know the patient. I have to know, in the case of prostate cancer, what makes him tick. And so I think there's going to be tremendous upside for these hope enhancement techniques, not just using it for hope's sake but also for these other epiphenomenon in medicine, like adherence and like decision making, that we speak about all the time, but I wonder to what extent we're really committed to doing a better job on those parameters. ASCO Daily News: Right. Do you see a role for technology to grow hope enhancement workshops, to make them accessible to more people in other parts of the world, in other medical settings? How do you think technology has changed the way people confront the experience of illness? And what role do you think you can play in this? Dr. Benjamin Corn: Yeah. Well, I guess all of us were brought in very rapidly, sometimes kicking and screaming, into this new era. And health care providers are smart, and they're resourceful, and they've figured out a way to ride this challenging wave that COVID has brought into our lives, this tsunami, if you will. So COVID has pushed us all into digital health. My organization, Life's Door, which developed an application, a smartphone app, called Hopetimize--kind of a  play on the words "hope" and "optimize"--in other words, the idea is to optimize your life with using these hope techniques I described before. So we had a game plan to get to digital work in the year 2022. That was a strategy that we basically developed about 5 years ago. When COVID came along, we realized that we had this wonderful product called hope enhancement workshops that we thought could really help oncologists who we thought could help their patients. But we couldn't get people together because of the new criteria for social distancing. So what was once a tailor-made concept for intimate settings with 15 people, I can tell you that even in our IRB-approved protocol--and people can see this on nih.gov, clinicaltrials.gov--our protocol specifies the kind of environment one has to have to conduct these workshops when you're doing it face to face. But that just couldn't happen for a full year, maybe a little bit more than that. So we very quickly developed the smartphone app, and we found a way to move our entire workshop to a Zoom platform. And we'll have some data that we'll be sharing that basically says that we can do it just as well with the Zoom platform as doing it face to face. And what's more, it gives more people access to the technology. It allows for more sustainability because we're not only using Zoom, we're using different social media outlets. Most of the literature on hope enhancement--it's sometimes called hope augmentation--can demonstrate a spike in hopefulness after such an intervention. But the challenge then becomes how to sustain that hopefulness, and that's not easy. Well, by creating these digital communities of hopefulness, with the aid of different social media, we think that maybe this is exactly how we can deal with the sustainability question. And finally, this kind of technology gives us scalability. I mentioned before that we've been approached by groups around the world, throughout Europe, now throughout Asia, parts of Africa, not to mention North America. Haven't heard much from South America and Antarctica now that I'm thinking about it, so we're waiting for you guys. But we could never--all of us--I'm a busy physician as well. So there's a limit to how many times my colleagues would have to cover me when I say, "Oh, I'm off on another trip, teaching these hope techniques to people." But once we have it on Zoom platform, and we can bring, let's say, 15 to 20 people into the experience by bringing them into a Zoom room, I don't have to go anywhere. I can do it right from my living room, just like they're in their living room. And it sounds very simple, but I don't think anybody would have really imagined that we could be on our way like this if you sat down to contemplate this upside of 2019. ASCO Daily News: Right. And do you feel the response from the oncology community, from your peers across the world, has been quite positive? Scientists are sometimes skeptical about things such as hope enhancement techniques. Or have you found that not to be the case? Dr. Benjamin Corn: Yeah. That--so there's another example. I think that a barrier is the working assumptions of, let's say, my colleagues--let's say, me myself before I got into it. I mean, we're trained in a truly biological, scientific model. We talk about a biopsychosocial model, sometimes a biopsychosocial narrative model, but at its core, we pride ourselves as being scientists, and this kind of an idea was very off-putting to a lot of people. When we started publishing on this and the word got out that there were actually reproducible results showing that we can enhance hopefulness, people said, "Wait a second. I'm having a problem myself with patients who are just not hopeful." "Wait a second. I'm having a problem myself with my own burnout and my own compassion fatigue." And these colleagues have been seeking this out now in droves. And what our challenge has been right now is to be training facilitators so that we can really fan out and make sure that we answer this need of people saying, "I want to learn these techniques." Again, not just hope for hope's sake--I mean, I'm for hope. But for all the other upsides that we mentioned before--anti-burnout, increased adherence, probably bettered medical decision making--I think these are the motivators for people as opposed to just saying, "Make me more hopeful." So whatever gets you to the workshop, I couldn't care less. Everybody comes with their own reasons. That's always quite fascinating to hear why somebody decided to enroll in one of our workshops. But once people are there, most of them find that they really benefited from it. Typically, if we do a workshop with 20 people, the next day, we'll get a third to 40% of the participants saying, "You know what? I love this so much. I took these techniques, and I called in my children after dinner, and we talked about their goals and what struggles they're having in trying to reach the goals." So to me, that's very touching. And to get through your earlier question about the impact of this thing in communities outside of medicine, I think we're really on the cusp of forming what I like to describe as communities of hopefulness. And I think, again, we saw that in the COVID era. There was, in particular, a community in London that was very interested and brought us in also for a series of four workshops. And one of the things that we're working on right now in a hospital setting is what we call the seal of hopefulness. And that's based on, when I was growing up, this notion of the Good Housekeeping Seal of Approval. Well, we want to be able to approach hospitals and to say, "Just like you like to go through the accreditation process, perhaps you want to go through this process of making your staff more hopeful." Patients pick up on these things. So imagine, Geraldine, a world in which the physicians were taking care of you and the people you love, the nurses, the orderlies who bring them down to CT scans and the MRI. There's a lot of time that a patient in a hospital spends outside his or her bed. Imagine if en route to having a study, which you're very anxious about, you have somebody who's been trained and knows how to speak to you about your goals and your value. I think that would be the kind of environment I'd want to be taken care of in. I mean, of course I want to know that the knowledge base is top shelf. But could you imagine if there was this hope seal on the door that said, "People here really give a damn. They care about you, not just your tumor, and that is their commitment." I think that can be very reassuring. And we've begun to pitch that idea to hospital administrators, both in Israel, where I'm based, and in large-scale hospitals both on the community level and the academic level in the U.S. and Canada. ASCO Daily News: Excellent. Thank you so much, Dr. Corn, for telling us about your innovative work today. You really seem to be having a great impact. And I thank you very much for taking the time today. Dr. Benjamin Corn: Thank you. It was a pleasure. ASCO Daily News: And thank you to our listeners for your time today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclosures: Dr. Ben Corn: None disclosed.  Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Dr. David Freyer, professor of clinical pediatrics at the University of Southern California; Dr. Michael Roth, director of the AYA Program and Childhood Cancer Survivorship Program at The University of Texas MD Anderson Cancer Center; and onco-fertility expert Dr. Leslie Appiah, associate professor of Obstetrics and Gynaecology at the University of Colorado Anschutz, weigh in on the challenges and advances in care for adolescents and young adults with cancer and survivors. Transcript ASCO Daily News: Welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. On today's episode, we'll discuss the unique challenges facing adolescents and young adults with cancer. I'm delighted to welcome three experts for this discussion. Dr. David Freyer is a professor of clinical pediatrics, medicine, and preventive medicine at the University of Southern California's Keck School of Medicine. Dr. Michael Roth is director of the AYA Program and Childhood Cancer Survivorship Program at The MD Anderson Cancer Center. And Dr. Leslie Appiah is associate professor of obstetrics and gynecology and director of the Fertility Preservation and Reproductive Late Effects Program at the University of Colorado and Children's Hospital Colorado. My guests report no conflicts of interest relating to our discussion today, and full disclosures relating to all episodes of the podcast are available on our transcripts at ASCO.org/podcasts. Dr. Freyer, Dr. Appiah, and Dr. Roth, it's great to have you on the podcast today. Dr. David Freyer: Thanks, Geraldine. It's really great to be here. Dr. Leslie Appiah: Thank you for having us. It's our pleasure. Dr. Michael Roth: Yeah, really great to be here. ASCO Daily News: So today we're highlighting some of the issues and strategies you all presented during the ASCO Annual Meeting that addressed equity issues and strategies to improve outcomes for AYAs. Our listeners will find a link to the presentation in the transcript of this episode. Dr. Freyer, there are approximately 89,000 AYA patients diagnosed with cancer in this country each year. Tell us about the challenges they confront and why they're so vulnerable to health care disparities. Dr. David Freyer: Absolutely. I'd like to say, first of all, thanks, Geraldine, for the opportunity for us to participate in this podcast. I think, as your question points out, AYAs who developed cancer are in a sort of double jeopardy, because not only of the challenges of cancer, but also their life stage where there's so much change and vulnerability. Normal changes for AYA life stage differ across the spectrum. 15 to 39 years is a very broad range. And at the younger age, I would say in the 15 to 21-year-old group, these challenges commonly involve education. It's finishing high school, possibly education or trade school, pursuing a career or vocation, expanding and reorienting their social network from their nuclear family, experiencing serious relationships for the first time, and then starting to explore intimacy and sexuality. For that younger group, self-image and physical appearance is very, very important. And there's overall a move toward greater personal autonomy and independence. When you get into the middle years, roughly [ages] 22 to 29, I would say that the issues begin to take on a financial character. It's becoming financially independent, paying for housing, starting or maintaining their own health insurance, maybe having their first meaningful employment. And a great many in this group are saddled with substantial debt from previous education. And then in this age group, they're starting to identify significant partners for the first time. And then finally, in the later years, roughly [ages] 30 to 39, the concerns really begin to focus on career advancement, maintaining a home life, starting or building families, raising children, taking on new financial obligations of adulthood like owning a home. And interestingly and importantly, some in that latter phase, we're seeing more and more, are beginning to feel the pinch from above as they're beginning to take care of unwell or older dependent parents who also need the financial support of this normally productive age group. So there's this developmental continuum. And to add cancer on top of all of that is, to say the least, highly disruptive. So even the experience of being treated for AYA cancers that have a good prognosis, and many do nowadays, it still interrupts education, delays career starts and return to work, upends their social networks, [and] undercuts their independence. They revert to being dependent on their nuclear family, and they have enormous financial burden. And then on top of all of that, of course, many of these patients are dealing with long-term health problems, because they have late effects from their treatment. And so to get your point about why this is an equity issue, I think that this session is perfect for this 2021 ASCO meeting actually, because AYAs, it's a cancer population that's defined by age. It's characterized by life stage dependent challenges. And so for that reason, they're systematically disadvantaged in ways that other cancer populations are not. And that's the definition of health care disparity. So they need special support in all these areas. And as a final note, I would say that AYAs who represent other disadvantaged cancer populations, such as low income or racial and ethnic minorities, I mean, they're actually in triple jeopardy, because they're at the intersection of their age, cancer, and also their background social status. ASCO Daily News: Absolutely. AYAs confront a host of disparities. AYAs frequently identify fertility threat as a major concern, and many patients have suffered fertility loss due to the effects of treatment. Thankfully, there continues to be much progress in fertility preservation, but not everyone has access to this care. Dr. Appiah, you've done a lot of work in onco-fertility and have even engaged with legislators to help pass bills mandating insurance coverage of fertility preservation for patients with cancer. Can you tell us about best practices in fertility preservation and your concerns that not all patients and survivors have access to available technologies? Dr. Leslie Appiah: Thank you, Geraldine, for that question. As you stated, with 80,000 plus AYA patients being diagnosed a year, we know that there are approximately 100,000 survivors. And so survivors are living longer. Up to 75% of them will experience at least one adverse event or late effect of their cancer therapy. Infertility, as you stated, is the most prevalent, one of the most discussed reproductive late effects in the literature, affecting up to 12% and 66% of female and childhood cancer survivors respectively. And then in addition to the infertility or fertility-related effects, there are other reproductive late effects that cancer survivors experience. And so as in many aspects of adolescence and young adult care, disparities also exist in onco-fertility or fertility preservation. The governing bodies of our societies--so the American Society for Reproductive Medicine, the American Society of Clinical Oncology--have all put out consensus statements describing how we should be caring for this population and how we should be providing equal care to these patients (DOI: 10.1200/JCO.2018.78.1914). And all of the societies or the guidelines recommend that physicians inform every patient of reproductive age about the risk of therapies to fertility and the options for fertility preservation. And by reproductive age, we mean from birth through, typically, for women age 42 and our male counterparts can be fertile much later into 50s and 60s. And so all of these patients should be counseled about the risks and then referred or offered the opportunity to see a reproductive specialist for further counseling, and that this really should occur before any treatment is provided. We know that once patients receive any cancer therapies that our options are limited in terms of what we can provide them for fertility preservation. So this conversation should occur regardless of the patient's age, gender, culture, socioeconomic status, or health care team bias. And these discussions should continue into survivorship, because even at the end of therapy, there may be some options for these patients. Despite recommendations, however, less than 50% of patients ever recall having these discussions with their providers, and then less than 30% of patients go on to use fertility preservation therapies. This disparity is sometimes due to information overload. Many times the patients don't recall the discussion, even though the discussion was had. But really when we look at the data, many times they are not being offered this information. We know that in terms of disparities, men are more often referred for counseling and referred for fertility preservation therapies because of the idea that it's easier to bank. And for those men who are feeling well and are of age, sperm banking can be a simple process. But many of these patients are very ill, and so extracting sperm becomes an issue for them and it becomes very challenging. We know that patients with fewer financial resources are less likely to be offered fertility preservation counseling. So our patients in the lower socioeconomic statuses, these patients are less likely to be referred. And again, that's not providing equitable care. There are many resources available for patients that can provide some financial resources. And so these patients really should be given the opportunity to have a discussion and seek resources, or we can provide options for them. And then lastly, I'll say that in terms of disparities, cultural biases play a huge part in this. Our providers come with their own biases as to how many children they feel that a family should have, and that can be a bias. Sometimes prognosis can be a form of bias. If the patients have a poor prognosis, then perhaps the provider is uncomfortable referring them for fertility preservation therapy. But there are some options for patients if they should succumb to their cancer diagnosis, there are some posthumous reproductive options that our young adults can participate in or agree to. And it requires a lot of legal discussion and documentation and contracts, but there are options. And we really should be providing our patients the opportunity to decline these options. And in that way, we can really address the disparities in fertility preservation for our patients. And then lastly, I will say cost is a factor, but there are I think now 13 states with insurance mandates for fertility preservation. And these mandates are starting to occur more and more often. And so we need to continue to push our legislatures to move the needle forward in this way. ASCO Daily News: Can you highlight some of the new technologies in fertility preservation that oncologists should be aware of? Dr. Leslie Appiah: Absolutely. I think two of the very important aspects of this is that we are able to provide fertility preservation for adolescents in terms of egg freezing. So until recently, we limited this option for girls who were 18 and older or late adolescents, but we now can provide egg freezing for girls once they reach puberty, and especially once they are monarchal or have achieved menses. And so that is something that we really want our oncology colleagues to know. It's also important for our colleagues to understand that we can start for egg freezing at any point in the patient's menstrual cycle. Historically, the patient needed to be on their cycle in order to stimulate, but now we have random start protocols. So if we see a patient today, we can start stimulating tomorrow or the next day. And the average number of days to stimulate the ovaries to be able to grow eggs to freeze is about 10 to 12 days. And so we really can intervene for these patients if we are informed of their diagnosis very early. And in that way, there will be no delay in their cancer therapies. And then lastly, we are very excited to share that ovarian tissue freezing is no longer experimental. As of December 2019, the experimental ban was lifted by the American Society for Reproductive Medicine and ASCO. And so patients from birth through age 40 can have an ovary removed, or part of an over removed, and frozen for their future fertility. And this is considered clinical care. We're able to put this through the insurance, and therefore alleviate the financial burden on many of our families. ASCO Daily News: That's great, Dr. Appiah. Thanks for highlighting these positive developments in fertility preservation. Managing the care of AYA patients and survivors as they age and deal with toxicities from treatment and other physical and mental health issues requires collaboration between providers. Dr. Roth, can you share some strategies to address the unique challenges of AYAs and the providers who care for them through various phases of their lives? Dr. Michael Roth: Thank you, Geraldine, for that important question. As Dr. Appiah and Dr. Freyer clearly noted, AYAs face many unique challenges both during and after cancer treatment. And it really is essential that, as medical providers, we seek to meet and treat these challenges. Unfortunately, the system as it's currently set up is really not well suited to care for some of these unique needs. Specifically, many of our younger AYAs who deal with cancer such as leukemias and lymphomas, they're treated within the pediatric oncology department. And often, the approach to their care is focused on the care of younger children. On the flip side, many patients in their 30s with breast cancer, colorectal cancer, these AYAs are treated within the medical oncology community and are often seen in clinics with many older adults. So most of the care across the country is not specifically tailored to the unique needs of AYAs, and that's really where collaboration comes specifically into play. We know that there are many opportunities to address these psychosocial needs, the education and work needs, the onco-fertility needs, the genetic counseling needs of our AYAs, but it really takes a champion, or a number of champions, at each site to ensure that AYAs needs are prioritized. Recently, there has been a large growth in the number of AYA programs. And what a number of institutions have done is they've brought medical oncology together with pediatric oncology to centralize these specific AYA resources under one house. Some of these AYA programs are treatment-based programs. For example, some sites have an AYA heme-malignancy program, where they will provide both the cancer care, as well as the supportive care required for their AYA patients with leukemias and lymphomas. Other AYA programs are purely supportive care-based programs, where patients will be referred to them for their onco-fertility needs, for their psychosocial health needs, for their education and work needs as well. At the end of the day, we really just need to do what's right for our patients. And we've learned over many, many years that just treating our AYAs the same as we treat our younger children, or just treating our AYAs the same as we treat our older adults, doesn't cut it. And we really need tailored, focused approaches to make sure that we both optimize cure rates, as well as to optimize health-related quality of life for these patients both during and long after treatment. ASCO Daily News: Right. So Dr. Roth, what will it take to improve collaboration between providers? Dr. Michael Roth: Cancer care is traditionally very siloed. And these silos do decrease the rate of progress in which we can make within cancer care. But specifically within AYA oncology, historically, pediatric oncologists did not interact much with medical oncologist. By having AYA tumor boards, by having more multidisciplinary clinics, essentially you're taking down those barriers. You're breaking down those walls. And being face to face, or now in the virtual world, being able to connect and to collaborate, it really allows the optimization of care for our AYAs. It's not possible to know everything about every AYA oncology diagnosis. And when you're in a large academic center, you often have many subspecialists within each of the different cancer types. When you're in a smaller community setting, oftentimes you have more generalists who take care of all patients with a large number of diagnoses. And often in the community settings, there aren't many specialists who focus on AYAs with breast cancer or young adults with colorectal cancer. And oftentimes, it really takes teamwork and a real consensus and an approach within a team setting to make sure that both the cancer-directed care is appropriate and is the most appropriate treatment approach, but also there's a need to focus on that health-related quality of life, and specifically that often gets lost for many of our patients during their treatment. Dr. Leslie Appiah: We are also finding that when we incorporate our fertility preservation colleagues, our experts, into the multidisciplinary oncology meetings that were also able to break down those silos and help educate our colleagues about fertility options for patients as they are diagnosed. And that really does expedite the care that we provide to these patients. We also want to look at leveraging technology to improve how we incorporate fertility preservation into oncology care and using our best practice advisories within our Epic systems, as well as using the Epic referral process to really expedite the referrals of patients. And by that I mean, there are ways to do an opt-out referral system where the referral is automatic, unless the oncologist opts out of that referral. And in order to opt-out, the oncologists will have the discussion with the patient about their fertility risk and then recommend consultation. And the patient can then decline, and that's when the provider would opt-out of that consult. So utilizing technology that we have already can really expedite the care for these patients and break down some of those barriers. ASCO Daily News: Absolutely. Well, there's a huge need for more research on AYAs. Dr. Freyer, how does clinical trial accrual among AYAs compare to older patients? Are there any innovative strategies that could improve trial accrual among this patient population? Dr. David Freyer: This is a really important issue, and I'm glad you raised it, Geraldine. So clearly, to continue advancement of AYA oncology and really every realm, whether it's survival or supportive care, more epidemiology studies, studies on basic biology questions about cancer types in this age group, long-term outcomes, and so forth, we can't make any advancements in AYA or any other age without conducting the research. Clinical trials for many years have been sort of the heart and soul of clinical oncology science, because it's actually testing new questions, new therapies, and following in an organized way the outcomes of the patients who are enrolled in clinical trials. The problem is that the proportion of AYA patients who are enrolled in clinical trials is exceedingly low. The gold standard, I think, or benchmark for clinical trial enrollment actually tends to be children, pediatric oncology, which for decades has been very, very successful at enrolling patients on clinical trials. And they have improved survival and improved knowledge around cancer to show for that effort. So most studies--there's a little bit of variation--but most studies indicate that about 20% to 40%, at any given time, of children enroll on a clinical trial if they're newly diagnosed with cancer. For AYAs, that number is less than 10%, usually more around 5%. And that's actually similar to older adults. The drop off occurs sometime between 15 and 20 years of age in terms of enrollment on clinical trials. So the question is, how can AYA patients--how can the picture be shifted to look more like that of younger children? And it turns out, I think it's really a complicated scenario. There's multiple levels to this problem. Part of the challenge is having the right kinds of trials available for the diseases that occur in adolescents and young adults. And then another layer is getting those trials that are developed by the, say, the National--the NCTN Oncology groups getting those opened up at the sites where the AYA patients are being treated. There are a lot of barriers that institutions need to overcome in order to get those trials opened up. And if they can be opened up, then they're available to the AYA patients. But it doesn't stop there. Then the next step is that you've got to get those trials presented to the AYA patients. So the pediatric or medical oncologist that's taking care of the children--or excuse me, the AYA patients--need to be aware of these trials. They need to have access to research infrastructure that can make it feasible to offer these and enroll the patients. And then finally, of course, the AYA patient himself or herself needs to be convinced that this is the right thing for them to do and to go ahead an enroll on the clinical trial. So there's multiple steps to this. And clearly, addressing any single step won't ensure that more AYAs are being enrolled into clinical trials. So it requires a multi-level, multipronged approach. I think, in terms of innovative strategies, again, it's all of these things at one time. So on the national level, there's a good deal of work being done to try to increase the collaboration across the different NCTN groups--the National Cancer Institute (NCI) National Clinical Trials Network groups, the adult groups, and children's oncology group--to increase collaboration across those groups. So that there are more trials being opened that are appropriate for that entire spectrum of 15 to 39 years of age, which, as Dr. Roth pointed out earlier, cannot be addressed without collaboration between the pediatric and the medical oncology groups. So trying to pull those together. And then on the delivery end to the patient, trying to find better ways to support our oncologists and to make the information about clinical trials more digestible, more maybe less threatening, more understandable to AYA patients, so that they can make a good, well-informed decision for themselves. Perhaps the least exciting for most of us, but in some ways maybe the most crucial and the most overlooked, is that middle stage of getting these trials opened at the sites. That requires resources to get these passed through the IRBs at the institutions. It takes resources to have clinical research coordinators there to shepherd them through the regulatory processes and then to make those readily available to the practicing oncologists. I think at the local level, that's where some of the greatest challenges are. And I think one of the factors that sort of feeds and aggravates or exacerbates the health disparities issue for AYA patients is where these patients are being treated. There are a number of studies that show that AYAs tend to be treated at community sites rather than traditional academic centers. And that's wonderful in terms of making health care accessible to these patients in their home communities. There's a lot to be said for that actually. But one of the features of that treatment setting that may undercut the clinical trial question at least is that some sites, many of them, don't necessarily participate in a regular way or have fewer resources to participate in the clinical trial enterprise. So those patients, if they're treated in the convenience of their home community, they may not have access to the same sorts of clinical trials of those who are treated in academic centers. We need to figure out a way to overcome those kinds of challenges. It's not easy. ASCO Daily News: Right. Dr. Roth, what are your thoughts on clinical trials for AYAs? Dr. Michael Roth: So a couple of the layers that Dr. Freyer addressed in terms of barriers to enrolling more AYAs in clinical trials, I do think at the national level, we've made a lot of progress over the past decade with these collaborations within the NCTN network groups. Currently, we have a record number of truly AYA collaborative trials open and available for our sites to be able to have available for their local patient population. And like Dr. Freyer said, a lot of these trials, they're really getting stuck at the local level because, in many ways, there's not an incentive to open the AYA trials when you have limited resources, because it's easier to enroll many more patients on the prostate cancer trial or the older adult breast cancer trial just due to patient numbers. So we really do need to overcome that large barrier of when we have trials available at the national level, they need to be opened up at all sites really across the board to make sure that our AYAs have access. The other point on the local level is to address the challenges we have in lack of knowledge on disparities in AYA enrollment and care. And we've tried to overcome that by having local AYA site champions, having folks on the ground really spreading knowledge. These folks typically are investigators, sometimes they work in the research office. And their goal is to help prioritize the opening, activation, and enrollment on AYA specific trials. There's still a lot of work to be done. It's a complex situation, but I do believe we are chipping away at many of these issues. ASCO Daily News: Great. I'd just like to wrap up with a final question about models of survivorship care delivery. So AYA patients who complete treatment need to be supported. They need appropriate follow up to monitor treatment-related health problems and psychosocial support. Dr. Freyer, what are the models of survivorship care delivery that can successfully address these needs? Dr. David Freyer: I think, again, similar to the clinical trial situation that we just discussed, I think that survivorship care for this population--in other words, patients treated during the 15 to 39-year-old age group--is in a process of emerging and growing and taking many of its leads from the pediatric oncology experience. Survivorship care in pediatric oncology is well established. It's been now decades in the development. And there's been a huge amount of research, really high quality research, done to map out the spectrum of late effects of cancer treatment, both medical and psychosocial, for patients who are treated. Those children then grow up into adulthood and they become AYA patients, but they were treated as younger children. So that landscape is pretty well mapped out, and there are excellent models of care in place around the country. That has now become the standard of care in pediatric oncology for comprehensive holistic care of these patients long term. That situation is emerging in AYA oncology--in other words, for patients treated in the 15 to 39-year-old age group. Of course, part of what drove that in pediatrics is that survival rates improved so dramatically that these issues were staring oncologists in the face. And it was absolutely necessary to deal with it. It's taken a little bit longer for survival to come up to those levels in AYA and older adults, but we're there in many cases. And with the high survival now that we're seeing in the AYA age group, the same question is begging itself as was in pediatric oncology, which is now we've got these patients who have completed treatment with all of the problems that you just mentioned. I mean, many do very, very well. And it's important not to paint a more negative picture than is warranted, but I think the data are beginning to show that many long-term survivors of AYA cancer also deal with health problems that are getting superimposed on the normal problems of aging that all human beings develop over time. Now how to deliver that, again, the experience is just emerging. I think that different centers have developed programs that sort of play to their own strengths and overcome their own challenges, just like Dr. Roth said with AYA programs and I'm sure Dr. Appiah could say about fertility preservation programs. Every place has its own experience of one. And while there are some common themes, there are some things that need to be addressed that are individual. I think probably the basic requirements for a survivorship care model for AYA patients is having somebody, a champion, who has some expertise in this area, commitment on the part of the facility to put together at least the basic resources to begin to bring these patients together. There are different kinds of models. The models can be doing survivorship care in the context of each disease team. Breast cancer may have their own survivorship focus, colorectal cancer, leukemias and lymphoma, and so forth. And they may be delivered within the context of the diseases or another model is, I would say, more the classic pediatric model, which is to have a survivorship clinic that can meet the needs across these different diagnoses. And it's important for each program to determine these for themselves. I'll put one final closing pitch in for the clinical research, which is needed in this area as well. Just as clinical trials are needed to improve survival with treatment and also our understanding of these diseases and the cancer hosts that the AYA [patients] represents, there's also a need for research in the long-term as well. And the best way to do that is in the context of survivorship efforts that are organized and have resources like databases and participation in larger cohort studies, so that we can begin to amass the data in the same way that we've done for children. Dr. Michael Roth: So, I completely agree with Dr. Freyer. I think AYA survivorship is still in its infancy. And we're really only learning now about what happens to our patients diagnosed as AYAs with cancer in 15 years, 20 years. What are some of the cardiovascular events that are happening in these patients as they age into their 50s, early 60s? I think there's a real need for standardization of how we care for our AYAs post-treatment based on exposures, based on cancer diagnoses. And currently, with the models in place for survivorship within some of the large institutions, there's a lack of standardization across departments, and then across institutions as well. There really are no set guidelines as to how do we monitor for cardiotoxicity. What should we be doing in terms of monitoring for psychosocial health concerns? And I worry even more, as you go into the community setting, that many of these sites don't have the resources to offer expert survivorship care. As Dr. Freyer mentioned, this is really a plug, a call to action, to focus more attention on our patients' lives, not just during treatment but well beyond treatment. We know that 5-year overall survival for AYAs is approximately 85%. So the majority of our AYAs diagnosed with cancer will live long and well past beyond their cancer diagnosis. And it really is essential that we help them live long, healthy, and happy and productive lives. Dr. Leslie Appiah: And I will add one final word to that. So the U.S. news and World Report reporting system has now started to include fertility preservation as a marker of providing excellent care in the children's hospitals. And of course, that's going to go into the adolescent population as well. So I think that's one impetus for our colleagues and our institutions to really make this a priority. Additionally, as Dr. Roth stated, using national databases, where we can really bring together all of the information so that we can standardize how we care for this population, is really important. And the University of Colorado is developing a national database in fertility preservation as a data coordinating center for the Oncofertility Consortium and will be including various sites across the country, so that we can start to look at this data longitudinally. And then lastly, I would say, again, leveraging technology. I don't think that, in medicine, we utilize technology the way that we should. And I think using our electronic medical record to signal to us, as fertility specialists, when a patient has completed their treatment and they are in survivorship, this is a time for us to intervene again into this patient's care and to make sure we've really addressed all of their fertility and reproductive and gynecologic/urologic needs that they are going to experience. So those are the ways that I think we can incorporate better fertility preservation care into the survivorship care model. ASCO Daily News: Excellent. Thank you, Dr. Appiah. And thank you, Dr. Roth and Dr. Freyer as well, for highlighting the challenges facing AYAs and approaches in care for this patient population. Dr. David Freyer: Thank you, Geraldine. Dr. Leslie Appiah: Thank you for having us. It's been a pleasure. Dr. Michael Roth: Thank you so much. ASCO Daily News: And thank you to our listeners for joining us today. If you've enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts.     Disclosures: Dr. Michael Roth Research Funding: Eisai, Pfizer Dr. David Freyer: None disclosed.  Dr. Leslie Appiah: None disclosed. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

CardioNerds (Amit Goyal and Daniel Ambinder), join cardiology fellows from the University of Chicago, (Dr. Mark Belkin, Dr. Ian Hackett, and Dr. Shirlene Obuobi) for an important discussion about case of a woman presenting with implantable cardioverter-defibrillator (ICD) discharges found to be in ventricular tachycardia (VT) storm and work through the differential of ventricular arrhythmias, etiologies of heart failure, and indications for permanent pacemaker and ICD placement. Advanced imaging modalities that aid in the diagnosis of cardiac sarcoidosis, manifestations and management of cardiac sarcoidosis are also discussed. Dr. Nitasha Sarswat and Dr. Amit Patel provide the E-CPR for this episode. Audio editing by CardioNerds Academy Intern, Leticia Helms. Claim free CME just for enjoying this episode! Disclosures: Dr. Amit Patel disclosed ownership of small stocks in GE Healthcare Bio-Sciences. Jump to: Case media - Case schematic & teaching - References CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Case Media Click to Enlarge Episode Teaching Pearls The etiology of wide-complex tachycardias (WCT) of ventricular origin can be broken down by structurally normal versus structurally abnormal hearts. WCT in structurally normal hearts can be further broken down into idiopathic or primary arrhythmia syndromes. WCT in structurally abnormal hearts can be broken down into ischemic and non-ischemic etiologies.In patients with an unexplained non-ischemic cardiomyopathy, conduction abnormalities and/or ventricular arrhythmias should raise suspicion for cardiac sarcoidosis. Additional manifestations include atrial arrhythmias and  pulmonary hypertension.Accurate diagnosis and treatment of cardiac sarcoidosis often requires multimodality cardiovascular imaging. Check out these terrific videos from Cardiac Imaging Agora: 1) PET for inflammation/sarcoidosis and 2) Echo and CMR for sarcoidosis.While a pathological tissue diagnosis is the gold-standard, endomyocardial biopsy has a low sensitivity, weven when paired with image guidance. Remember to consider extra-cardiac sites for biopsy.Decisions regarding ablation of ventricular arrhythmia or ICD placement should be done individually with careful assessment of active inflammation secondary to cardiac sarcoidosis and possible response to immunosuppressive medications.Management of cardiac sarcoidosis has two basic principles: 1) Treat the underlying process with immunosuppression and 2) Treat the cardiac sequelae: heart failure, conduction abnormalities, ventricular arrhythmias, atrial arrhythmias, and pulmonary hypertension. Notes 1. The patient in this case was found to be in VT storm. Taking a step back, when we suspect a wide complex tachycardia (WCT) is VT, what are some etiologies we should keep in mind? Differentiating between a supraventricular vs. ventricular origin of a WCT will be a topic for a future episode! But after you have determined that the origin of WCT is ventricular, considerations for the underlying etiology should include ischemia-related, non-ischemic cardiomyopathy-associated, primary arrhythmia syndromes and idiopathic (in addition to common considerations such as medications and electrolyte abnormalities)Chronic ischemia-related WCT is typically scar-mediated, a result of re-entrant mechanism and more commonly presenting as monomorphic VT. WCT in the setting of acute ischemia is likely a result of combination increased automaticity and re-entry, typically manifesting as polymorphic VT.  In fact, acute ischemia is the most common cause of polymorphic VT, not Torsades de Pointes, and should be our first consideration. Torsades de Pointes specifically occurs due to an early afterdepolarization in a patient with an acqui...

On today's episode, Dr. Pamela Kunz, director of the Center for Gastrointestinal Cancers at the Yale School of Medicine, and vice chief of Diversity, Equity and Inclusion for Medical Oncology at Yale, discusses compelling sessions from the 2021 ASCO Annual Meeting that addressed gender disparities in the global oncology workforce and sexual harassment experienced by oncologists.   Transcript: ASCO Daily News: Welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. My guest today is Dr. Pamela Kunz, an associate professor of medicine in the division of oncology at the Yale School of Medicine where she also serves as the director of the Center for Gastrointestinal Cancers. Dr. Kunz also serves as the vice chief of Diversity, Equity, and Inclusion for medical oncology at Yale. Today, Dr. Kunz will highlight strategies to dismantle gender disparities in the global oncology workforce featured at the 2021 ASCO Annual Meeting. She will also tell us about the first study in oncology to systemically characterize the incidence of sexual harassment experienced by oncologists. Dr. Kunz reports no conflicts of interest relating to our discussion today and her full disclosures are available on the transcript of this episode. Dr. Kunz, welcome back; it's great to have you on the podcast again.  Dr. Pamela Kunz: Thank you so much. My pleasure to be here. ASCO Daily News: The theme of the 2021 ASCO Annual Meeting was Equity. Every Patient. Everyday. Everywhere.  Equity issues also apply to the oncology workforce and there were some very interesting discussions at the meeting on workplace disparities and harassment. You chaired an education session on dismantling gender disparities in the global oncology workforce. This session brought together a really interesting and diverse panel of experts  in medicine.  They discussed compelling data around gender disparities and steps to diversify leadership in medicine. They also looked at the role of male allies and how allies and advocates can support all women, and shared strategies on how to activate and empower female leaders.  Can you tell us more about this session? ("Dismantling Gender Disparities in the Global Oncology Workforce Together").  Dr. Pamela Kunz: Sure. This was--thank you for asking about that session. I think that really the theme of equity permeated so many different aspects of this Annual Meeting. And I think it was really inspiring and I think incredibly helpful to think about really reimagining how we provide cancer care. And I think I really like to think of workforce disparities as the other side of the same coin of patient disparities or inequities in patient care. I think that in order for us to provide equitable patient care, we really have to provide and create a diverse, inclusive, and equitable workforce. And so this is really one aspect of that is around gender disparities or, of course, other disparities in the workforce. And we actually do touch on that in one of the talks. So we put together a diverse panel that represents a number of different viewpoints. They were not all oncologists. In fact, I was the only medical oncologist on. Dr. Reshma Jagsi is a radiation oncologist. And Dr. Hannah Valentine is a cardiologist who was previously at the National Institutes of Health (NIH) and the inaugural director of their diversity program. Dr. Leon McDougle also spoke. He's a family medicine physician, the current president of the National Medical Association. And Mrs. Dee Anna Smith is the CEO of Sarah Cannon Research Institute. So we had this really incredibly diverse group of perspectives. And as you mentioned, we really touched on a whole variety of topics. I think it's also worth just mentioning kind of the scenes for this. This session originated well over 2 years ago. And I think that the timing of this now happening in 2021 following the pandemic I think was really incredibly important. I think we didn't really recognize it at the time. We were supposed to do this session last year in 2020. And it was really the 2020 planning committee that approved the session with Dr. Howard Skip Burris and Dr. Tatiana Prowell and Dr. Melissa Johnson. We had all these conversations of how do we get men in the room to talk about gender disparities? And we really crafted this panel to try to address a diverse audience and get everyone in the room. And then it was really so well timed with Dr. Pierce's ASCO theme of equity for every patient, every day, everywhere. It really just tied in nicely. ASCO Daily News: Excellent. What are the key takeaways here for oncologists?  Dr. Pamela Kunz: Sure. I can add some of that. I think that the first--and this was really addressed by Dr. Reshma Jagsi--is that we need to collect the data. We need to measure evidence of disparities at our institutions, in our organizations in order to really know where we're starting and in order to know how we're getting better. We have a lot of objective data already. But I think that I want to challenge all of our listeners to think about how can we be better about collecting that data in our own institutions. I think that the takeaways from Dr. Valentine's talk were some really wonderful concrete solutions to diversify the workforce. She took some lessons learned from programs she initiated at the NIH. And I'd like to specifically highlight a program at the NIH called the Scientific Workforce Diversity Toolkit. And in that, they instituted a program for cohort hiring in the Distinguished Scholars program. And this was bringing together a diverse group of underrepresented minorities and women into this scholars program. And they demonstrated really increased rates of female tenure track investigators. And I think that we can all do that in our institutions and organizations by instituting cohort hiring. From Dr. Leon McDougle's talk, he really highlighted this concept of intersectional feminism. And this term was coined by Kimberle Crenshaw. She's a professor of law at Columbia University. And it speaks to the fact that many marginalized characteristics or people who are in underrepresented groups may have characteristics that intersect. So that includes gender, age, sexuality, education, race, culture, ethnicity. And if any one person has a number of these characteristics, they may, in fact, increase the burden on that individual and may increase their risk for discrimination and for disparities. And I think it's recognizing the intersection. Intersectionality happens. And our women of color and our women who may have these other marginalized characteristics may be especially at risk. He also talked about a program at the Ohio State where he is on faculty entitled Advocates and Allies. And it's a National Science Foundation-funded program that trains men how to be advocates and allies. And then lastly, Miss. Dee Anna Smith spoke about creating a tapestry of allyship. She had this beautiful visual metaphor of really bringing together not just mentors. It's sort of modernizing the idea of mentorship and to really thinking more about allyship and how our trainees need to bring together, yes, perhaps mentors, but that allies really can represent an alternative to mentorship and a tapestry meaning that you need more than one person to serve as an ally for you. So I think those were--it it truly was--I moderated. I think these folks did all of the work in presenting. But it was really inspiring and I think very solution focused. ASCO Daily News:  Well, you were also the discussant of session that addressed a new study, Abstract 11001 on sexual harassment of oncologists. Now, few studies have used comprehensive validated measures to investigate the incidence and impact of workplace sexual harassment experienced by physicians and none, according to the authors of this study, by oncologists. So this is really important. What can you tell us about it? Dr. Pamela Kunz: Yes, absolutely. And I think the points that you made already really make this important and validate it. And I think the findings then in and of themselves are quite striking. So this group of authors led by Dr. Ishwaria Subbiah conducted a study. It was a cross-sectional survey of ASCO's research survey pool. And they then used the sexual experiences questionnaire, which is a validated questionnaire, as you mentioned. And this is really I think a real strength of the study. And they examined various aspects of sexual harassment. I think it's important for our listeners to understand the definition of sexual harassment. So this includes gender harassment, unwanted sexual attention, and sexual coercion. And gender harassment includes things that if we use the iceberg analogy, which they included in their presentation and was so nicely described in the NASEM, the National Academies of Science Engineering and Medicine report from 2018, the iceberg really underneath the surface contains many of these aspects of gender harassment that go unnoticed and unrecognized and include things like microaggressions. And in this study, they evaluated four downstream domains impacted by workplace sexual harassment including mental health, job satisfaction, sense of safety at work, and turnover intentions, meaning if an individual planned on leaving that specific job. And they looked at incidents of sexual harassment both by perpetrator, so institutional insiders or patients and families, and then by type of sexual harassment. So they received about a 30% response rate. They had 304 practicing oncologists access the survey link. And 273 provided responses. And I'll just hit some of the take-homes. So I think what I was struck by is the high rate of sexual harassment when the perpetrator is an institutional insider. So those are peers or supervisors. 70% of physicians reported one or more incidences of sexual harassment. This was higher in women. So, 80% of women reported sexual harassment compared to 56% of men. So, that was statistically different. But I was really struck by the fact that men were experiencing this as well. And then in terms of sexual harassment incidents when the perpetrator was a family or patient, 53% of physicians reported one or more incidences of sexual harassment. And this was 67% for women and 35% for men, also statistically significant. In terms of that difference. And then really a significant downstream impact from these experiences both for physicians who experienced this harassment from institutional insiders or from patients and families. And I think that we saw that really across the board for mental health, workplace safety, job satisfaction, and turnover intentions. And I think the take home for our listeners is that this can really lead to a significant loss of talent. And I think that if we are really hoping to--see, this is me editorializing. We are hoping to improve the diversity of our workforce because we know that that leads to better patient care and better patient outcomes. This is really important for our workforce to try to tackle and solve this problem of sexual harassment. ASCO Daily News: Absolutely. Well, thank you, Dr. Kunz, for highlighting some really important issues in oncology today. Dr. Pamela Kunz: Thank you so much. ASCO Daily News: Our listeners will find links to the two sessions discussed today on the transcript of this episode. And thank you to our listeners for joining us today. If you enjoyed this episode, please take a moment to rate and review us wherever you get your podcasts.   Disclosures: Dr. Pamela Kunz Stock and Other Ownership Interests: Guardant Health Consulting or Advisory Role: Ipsen, Lexicon, SunPharma, Acrotech Biopharma, Novartis (Advanced Accelerator Applications) Research Funding (institution): Lexicon, Ipsen, Xencor, Brahms (Thermo Fisher Scientific), Novartis (Advanced Accelerator Applications) Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Get .1 ASHA CEU hereEpisode SummaryYou're an awesome school-based SLP, the resident language expert, the speech closet hostess with the mostest. You're chugging along, doing your assessment thing, determining eligibility here, pushing into the classroom there, pulling kids out, chattin' with the teacher- you've got this! Then BAM!! This episode comes out of nowhere and reveals an unknown blind spot in our educational system, putting a serious snag in your assessment status quo. No worries, the Nerds and their experts have your back! This week, Dr. Trina Spencer and Dr. Doug Peterson step up once again with an eye-opening follow-up to their previous episodes on dynamic assessment (DA) and Multi-Tiered Systems of Supports (MTSS) for language assessment and intervention in schools. Tune in to go the extra MTSS and DA mile and learn about your essential role in the screening and prevention domain, an area of SLP not often explored, but so essential to a student's academic success. You'll drive away with a better understanding of the roles of language assessment beyond eligibility determination, along with (free but fabulous) tools you'll need to adjust for that screening blindspot and to help your education team set students up for language (and therein, academic) success. There's free stuff, witty banter, soap boxes, and MacGyvering. Don't miss out!You can learn more about Trina and Doug here.Learning Outcomes1. List the purpose of assessment and identify those necessary for MTSS.2. Describe the characteristics of curriculum-based measures.3. Explain how/why oral narrative retells are appropriate for screening and progress monitoring of language.Online ResourcesYou can access the free CUBED Assessment mentioned in this episode here.ReferencesPetersen, D. B., Spencer, T. D., Konishi, A., Sellars, T. P., Robertson, D., & Foster, M. E. (2020). Using parallel, narrative-based measures to examine the relationship between listening and reading comprehension. Language, Speech, and Hearing Services in Schools, 51(4), 1097-1111. https://doi.org/10.1044/2020_LSHSS-19-00036 Petersen, D. B., & Spencer, T. D. (2014). Narrative assessment and intervention: A clinical tutorial on extending explicit language instruction and progress monitoring to all students. Perspectives on Communication Disorders and Sciences in Culturally and Linguistically Diverse Populations, 21, 5-21. https://doi.org/10.1044/cds21.1.5 Petersen, D. B., & Spencer, T. D. (2012). The Narrative Language Measures: Tools for language screening, progress monitoring, and intervention planning. Perspectives on Language Learning and Education, 19(4), 119-129. https://doi.org/10.1044/lle19.4.119 Disclosures:Dr. Petersen and Dr. Spencer financial relationships: They are co-authors of the Story Champs curriculum and PEARL dynamic assessment. They receive royalties from the sales of those items. Dr. Spencer and Dr. Petersen have no financial relationships to disclose.Kate Grandbois financial disclosures: Kate is the owner / founder of Grandbois Therapy + Consulting, LLC and co-founder of SLP Nerdcast. Kate Grandbois non-financial disclosures: Kate is a member of ASHA, SIG 12, and serves on the AAC Advisory Group for Massachusetts Advocates for Children. She is also a member of the Berkshire Association for Behavior Analysis and Therapy (BABAT), MassABA, the Association for Behavior Analysis International (ABAI) and the corresponding Speech Pathology and Applied Behavior Analysis SIG. Amy Wonkka financial disclosures: Amy is an employee of a public school system and co-founder for SLP Nerdcast. Amy Wonkka non-financial disclosures: Amy is a member of ASHA, SIG 12, and serves on the AAC Advisory Group for Massachusetts Advocates for Children. Time Ordered Agenda:10 minutes: Introduction, Disclaimers and Disclosures20 minutes: Descriptions of the purpose of assessment and identify those necessary for MTSS15 minutes: Descriptions of the characteristics of curriculum-based measures. 10 minutes: Descriptions of oral narrative retells are appropriate for screening and progress monitoring of language5 minutes: Summary and ClosingDisclaimerThe contents of this episode are not meant to replace clinical advice. SLP Nerdcast, its hosts and guests do not represent or endorse specific products or procedures mentioned during our episodes unless otherwise stated. We are NOT PhDs, but we do research our material. We do our best to provide a thorough review and fair representation of each topic that we tackle. That being said, it is always likely that there is an article we've missed, or another perspective that isn't shared. If you have something to add to the conversation, please email us! Wed love to hear from you!Credits: Summary Written by Tanna Neufeld, MS, CCC-SLP, Contributing EditorAudio File Editing provided by Caitlan Akier, MA, CCC-SLP/L, Contributing EditorPromotional Content provided by Ashley Sturgis, MA, CCC-SLP, Contributing Editor Web Editing provided by Sinead Rogazzo, MS, CCC-SLP, Contributing EditorEpisode Summary__SLP Nerdcast is a podcast for busy SLPs and teachers who need ASHA continuing education credits, CMHs, or professional development. We do the reading so you don't have to! Leave us a review if you feel so inclined!We love hearing from our listeners. Email us at info@slpnerdcast.com anytime! You can find our complaint policy here. You can also:Follow us on instagramFollow us on facebookWe are thrilled to be listed in the Top 25 SLP Podcasts!Thank you FeedSpot!