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Dr. John Sweetenham and Dr. Erika Hamilton discuss top abstracts that will be presented at the 2025 ASCO Annual Meeting, including research on tech innovations that could shape the future of oncology. Transcript Dr. John Sweetenham: Hello, and welcome to the ASCO Daily News Podcast. I'm your host, Dr. John Sweetenham, and I'm delighted to be joined today by Dr. Erika Hamilton, a medical oncologist and director of breast cancer and gynecologic cancer research at the Sarah Cannon Research Institute in Nashville, Tennessee. Dr. Hamilton is also the chair of the 2025 ASCO Annual Meeting Scientific Program, and she's here to tell us about some of the key abstracts, hot topics, and novel approaches in cancer care that will be featured at this year's Annual Meeting. Our full disclosures are available in the transcript of this episode. Dr. Hamilton, it's great to have you on the podcast today, and thanks so much for being here. Dr. Erika Hamilton: Thanks, Dr. Sweetenham. I'm glad to be here. Dr. John Sweetenham: Dr. Hamilton, the Presidential Theme of the Annual Meeting this year is ‘Driving Knowledge to Action: Building a Better Future,' and that's reflected in many of the sessions that will focus on action-oriented guidance to improve care for our patients. And as always, there'll be great presentations on practice-changing abstracts that will change treatment paradigms and transform care. Can you tell us about some of the hot topics this year and what you're particularly excited about? Dr. Erika Hamilton: You're right. Dr. Robin Zon's theme is ‘Driving Knowledge to Action: Building a Better Future,' and you're going to see that theme really interlaced throughout the ASCO program this year. We had a record number of submissions. Over 5,000 abstracts will be published, and there'll be about 3,000 presentations, either in oral format or poster presentations. We have 200 dynamic sessions. Many of the discussants will be highlighting key takeaways and how we can translate action-oriented guidance to better treat our patients to build a better future. Our state-of-the-art science will include a Plenary Session. This will feature presentations as well as discussion of each of the presentations for clinical late-breaking abstracts. We have Clinical Science Symposia that I'm particularly excited about this year. These will feature key abstracts as well as discussions and a foundational talk around the subject. We're covering novel antibody-drug conjugate targets, turning “cold” tumors “hot” to include CAR T, as well as the future of cancer detection. There'll be rapid oral abstracts, case-based panels, and this will also feature interactive audience polling and case discussions. I also want to highlight the community connection opportunities. There will be 13 Communities of Practice that will be meeting on-site during ASCO, and there's also really a plethora of networking opportunities for trainees and early-career professionals, a Women's Networking Center, a patient advocate space, and I'm happy to report there will also be live music out on the terrace this year at ASCO. Dr. John Sweetenham: Well, that's going to be a really great addition. I have to say, I think this is always a special time of year because excitement starts to mount as the meeting gets closer and closer. And once the abstracts are out there, I certainly personally feel that the excitement builds. Talking of abstracts, let's dive into some of the key abstracts for this year's meeting. I'd like to start out by asking you about Abstract 505. This reports on 15-year outcomes for women with premenopausal hormone receptor-positive early breast cancer in the SOFT and TEXT trials. It assesses the benefits of adjuvant exemestane and ovarian function suppression or tamoxifen and ovarian function suppression. So, could you talk us through this and tell us what you think the key takeaways from this abstract are? Dr. Erika Hamilton: Absolutely. This is essentially the SOFT and TEXT trials. They are trials that we've been following for quite some time, evidenced by the 15-year outcome. And I think it really answers two very important questions for us regarding adjuvant endocrine therapy for patients that are facing hormone receptor-positive disease. The benefit of ovarian function suppression for one, and then second, the benefit of exemestane over tamoxifen, which is our SERM [selective estrogen receptor modulator]. So, in terms of the SOFT trial, when we talk about distance recurrence-free interval, which I really think is probably the most meaningful because secondary cancers, et cetera, are not really what we're getting at here. But in terms of distant recurrence-free interval, certainly with tamoxifen, using tamoxifen plus ovarian function suppression adds a little bit. But where we really get additional benefits are by moving to exemestane, an aromatase inhibitor with the ovarian function suppression. So, for example, in SOFT, for distant recurrence-free interval for patients that have received prior chemotherapy, the distance recurrence-free interval was 73.5% with tamoxifen, bumped up just a tiny bit to 73.8% with ovarian function suppression. But when we used both ovarian function suppression and switched to that aromatase inhibitor, we're now talking about 77.6%. It may seem like these are small numbers, but when we talk about an absolute benefit of 4%, these are the type of decisions that we decide whether to offer chemotherapy based on. So, really just optimizing endocrine therapy really can provide additional benefits for these patients. Just briefly, when we turn to TEXT, similarly, when we look at distance recurrence-free interval for our patients that are at highest risk and receive chemotherapy, tamoxifen and ovarian function suppression, 79%; 81% with exemestane and ovarian function suppression. And when we talk about our patients that did not receive chemotherapy, it increased from 91.6% up to 94.6%—very similar that 3% to 4% number. So, I think that this is just very important information when counseling our patients about the decisions that they're going to make for themselves in the adjuvant setting and how much we want to optimize endocrine therapy. Dr. John Sweetenham: Thanks so much for your insight into that. Dr. Erika Hamilton: Yeah, absolutely. So, let's turn to hematologic malignancies. Abstract 6506 reports exciting results on the new agent ziftomenib in relapsed/refractory NPM1-mutant acute myeloid leukemia. This is a phase 1b clinical activity study and safety results. This was the pivotal KOMET-001 study. And my question is, will this new agent fulfill an unmet need in this NPM1 space? Dr. John Sweetenham: Yeah, great question. And I think the answer is almost certainly ‘yes'. So, just as some brief background, NPM1 mutation is known to be a driver of leukemogenesis in around 30% of patients with AML, and it's a poor prognostic factor. And typically, about 50% of these patients will relapse within a year of their first-line therapy, and only around 10% of them will get a subsequent complete remission with salvage therapy. Menin inhibitors, which disrupt the interaction between menin and KMT2A, are known to be active in NPM1-mutated as well as in KMT2A-rearranged AML. And ziftomenib is a selective oral menin inhibitor, which in this study was evaluated at a dose of 600 mg once a day, as you mentioned, a phase 1b/2 study, which is multicenter and presented by Dr. Eunice Wang from Roswell Park. It's a relatively large study of 112 patients who were treated with this standard dose with relatively short median follow-up at this time. The median age was 69 years, and median prior therapies were two, but with a range of one to seven. And I think very importantly, 60% of these patients had previously been treated with venetoclax, and 23% of them had had a prior transplant. Looking at the results overall for this study, the overall response rate was 35%, which is actually quite impressive. Specifically for those patients in the phase 2 part of the study, around 23% achieved a CR [complete remission] or CRh [complete remission with partial hematologic recovery]. What's very interesting in my mind is that the response rates were comparable in venetoclax-naive and venetoclax-exposed patients. And the drug was very well tolerated, with only 3% of patients having to discontinue because of treatment-related adverse events. And I think the authors appropriately conclude that, first of all, the phase 2 primary endpoint in the study was met, and that ziftomenib achieved deep and durable responses in relapsed and refractory NPM1-mutated AML, regardless of prior venetoclax, with good tolerance of the drug. And so, I think putting all of this together, undoubtedly, these data do support the potential use of this agent as monotherapy and as a new option for those patients who have relapsed or refractory NPM1-mutated acute myeloid leukemia. So, let's move on a little bit more now and change the subject and change gears completely and talk about circulating tumor DNA [ctDNA]. This has been a hot topic over a number of years now, and at this year's meeting, there are quite a few impactful studies on the use of ctDNA. We have time to focus on just one of these, and I wanted to get your thoughts on Abstract 4503. This is from the NIAGARA trial, which looks at ctDNA in patients with muscle-invasive bladder cancer who receive perioperative durvalumab. Could you tell us a little bit about this study? Dr. Erika Hamilton: So, this was the phase 3 NIAGARA trial, and this is literally looking for patients with muscle-invasive bladder cancer that are cisplatin-eligible, and the addition of durvalumab to neoadjuvant chemotherapy. So here, this is a planned exploratory analysis of ctDNA and the association with clinical outcomes from NIAGARA. So, this is really the type of study that helps us determine which of our patients are more likely to have a good outcome and which of our patients are more likely not to. There were 1,000 randomized patients in this study, and 462 comprised the biomarker-evaluable population. There were about half in the control arm and half in the durvalumab arm. And overall, the ctDNA-positive rate at baseline was about 57%, or a little over half, and that had decreased to about 22% after neoadjuvant treatment. ctDNA clearance rates from baseline to pre-radical cystectomy was about 41% among those with durvalumab and 31% among those in control. And the non-pCR rate was 97% among patients with pre-cystectomy ctDNA-positive status. So, this really gives us some information about predicting who is going to have better outcomes here. We did see a disease-free survival benefit with perioperative durvalumab, and this was observed in post-cystectomy ctDNA-positive as well as the ctDNA-negative groups. Shifting gears now to GI cancer, Abstract 3506 is a long-term safety and efficacy study of sotorasib plus panitumumab and FOLFIRI for previously treated KRAS G12C-mutated metastatic colorectal cancer. And this is the CodeBreaK-101 study. What are your thoughts on this study? Dr. John Sweetenham: Yeah, thanks. A very interesting study, and this abstract builds upon the phase 3 CodeBreaK-300 trial, which I think has just been published in the Journal of Clinical Oncology. This showed that the combination of sotorasib and panitumumab improved clinical outcomes in patients with chemorefractory KRAS G12C-mutated metastatic colorectal cancer. The current abstract, as you mentioned, reports the CodeBreaK-101 trial. And this was a phase 1b trial where FOLFIRI therapy was added to sotorasib and panitumumab in previously treated patients with KRAS G12C-mutated metastatic colorectal cancer. The abstract reports the overall and progression-free survival results, as well as some updated safety and response data. So, in this study, patients with this particular mutation who had received at least one prior systemic treatment but were KRAS G12C inhibitor-naive were enrolled into an expansion cohort of the CodeBreaK-101 protocol. And these patients received what apparently now recommended as the standard phase 2 dose of sotorasib of 960 mg daily, plus panitumumab and a standard dose of FOLFIRI. And the primary endpoint of the study was safety, and secondary endpoints included confirmed response, overall response, and progression-free survival, as assessed by the investigator. And by November of last year, 40 patients had been enrolled into this study. Common treatment-related adverse events were cutaneous; some patients developed neutropenia, and stomatitis was fairly widespread. Discontinuation of sotorasib because of adverse events was only seen in 1% of patients, although patients did have to discontinue because of toxicity from some of the other agents in the combination. Looking at the results of this study, the updated objective response rate was 57.5%, and the disease control rate was estimated at 92%, going on 93%, with a median time to response of 1.6 months and a median response duration of 6 months. After a median follow-up of 29.2 months, the median progression-free survival was 8.2 months, and the overall survival 17.9 months. So, the authors have concluded that this combination, including sotorasib, panitumumab, and FOLFIRI, does appear to show quite promising long-term efficacy in pretreated patients with this specific mutation. The ongoing phase 3 study they mentioned, CodeBreaK-301, is aiming to evaluate this combination against the standard of care in the first-line setting for patients with KRAS G12C-mutated colorectal cancer. So, promising results, and we'd be very interested to see how this particular combination performs in the frontline. Dr. Erika Hamilton: Fantastic. Thanks so much for sharing that. Let's shift gears again and really talk about digital technology. I feel that we're all going to have to get much better with this, and really, there are a lot of promises for our patients coming here. There are a lot of abstracts at ASCO that are focusing on innovations in digital technology, including a really interesting psychosocial digital application for caregivers of patients that are undergoing hematopoietic stem cell transplantation. Can you tell us a little bit about this? It's Abstract 11000. Dr. John Sweetenham: Yeah, absolutely. This abstract certainly caught my eye, and I think it's intriguing for a number of reasons, partly because it's app-based, and partly also because it specifically addresses caregiver burden and caregiver needs in the oncology setting, which I think is especially important. And although the context, the clinical context of this study, is hematopoietic stem cell transplantation, I think it has potential applications way beyond that. We all know that caregivers of patients undergoing stem cell transplantation have significant quality-of-life struggles. They are well-documented to have significant psychological and emotional strain before, during, and after stem cell transplantation. And this abstract describes an application called BMT-CARE, which is aimed at improving caregivers' quality of life, caregiver burden, mood symptoms, and coping skills, and so on. So, this was a single-center, randomized trial from MGH [Massachusetts General Hospital] of this app for stem cell transplant caregivers, compared with usual care in those individuals. And the eligible patients, or eligible individuals, were adults caring for patients with heme malignancy undergoing either an autologous or an allogeneic stem cell transplant. Patients were randomly assigned either to use the app or for usual care. And the app itself—and I think it'll be interesting to actually see this at the meeting and visualize it and see how user-friendly and so on it is—but it comprises five modules, which integrate psychoeducation, behavior change, stress management, and they're delivered through a kind of interactive platform of educational games and videos. And then participants were self-reporting at baseline and then 60 days after transplant. So, around 125 patients were enrolled in this study, of around 174 who were initially approached. So, just over 70% uptake from caregivers, which is, I think, relatively high, and evenly distributed between the two randomized arms. And the majority of the participants were spouses. And at 60 days post-stem cell transplant, the intervention participants reported a better quality of life compared with those who received usual care. If you break this down a little bit more, these participants reported lower caregiving burden, lower incidence of depression, fewer PTSD symptoms, and overall better coping skills. So, the authors conclude that this particular app, a digital health intervention, led to pretty substantial improvements in quality of life for these caregivers. So, intriguing. As I said, it'll be particularly interesting to see how this thing looks during the meeting. But if these kind of results can be reproduced, I think this sort of application has potential uses way beyond the stem cell transplant setting. Dr. Erika Hamilton: Yeah, I find that just so fascinating and very needed. I think that the caregiving role is often underestimated in how important that is for the patient and the whole family, and really giving our caregivers more tools in their toolbox certainly is quite helpful. Dr. John Sweetenham: Absolutely. Well, the meeting is getting closer, and as I mentioned earlier, I think anticipation is mounting. And I wanted to say thanks so much to you for chatting with me today about some of the interesting advances in oncology that we're going to see at this year's meeting. There is a great deal more to come. Our listeners can access links to the studies we've discussed today in the transcript of this episode. I'm also looking forward, Dr. Hamilton, to having you back on the podcast after the Annual Meeting to dive into some of the late-breaking abstracts and some of the other key science that's captured the headlines this year. So, thanks once again for joining me today. Dr. Erika Hamilton: Thanks so much for having me. Pleasure. Dr. John Sweetenham: And thank you to our listeners for joining us today. Be sure to catch my “Top Takeaways from ASCO25.” These are short episodes that will drop each day of the meeting at 5:30 p.m. Eastern Time. So, subscribe to the ASCO Daily News Podcast wherever you prefer to listen, and join me for concise analyses of the meeting's key abstracts.   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.   More on today's speakers: Dr. John Sweetenham   Dr. Erika Hamilton @erikahamilton9   Follow ASCO on social media:  @ASCO on Twitter  ASCO on Bluesky  ASCO on Facebook   ASCO on LinkedIn     Disclosures:     Dr. John Sweetenham:     No relationships to disclose  Dr. Erika Hamilton: Consulting or Advisory Role (Inst): Pfizer, Genentech/Roche, Lilly, Daiichi Sankyo, Mersana, AstraZeneca, Novartis, Ellipses Pharma, Olema Pharmaceuticals, Stemline Therapeutics, Tubulis, Verascity Science, Theratechnologies, Accutar Biotechnology, Entos, Fosun Pharma, Gilead Sciences, Jazz Pharmaceuticals, Medical Pharma Services, Hosun Pharma, Zentalis Pharmaceuticals, Jefferies, Tempus Labs, Arvinas, Circle Pharma, Janssen, Johnson and Johnson   Research Funding (Inst): AstraZeneca, Hutchison MediPharma, OncoMed, MedImmune, Stem CentRx, Genentech/Roche, Curis, Verastem, Zymeworks, Syndax, Lycera, Rgenix, Novartis, Millenium, TapImmune, Inc., Lilly, Pfizer, Lilly, Pfizer, Tesaro, Boehringer Ingelheim, H3 Biomedicine, Radius Health, Acerta Pharma, Macrogenics, Abbvie, Immunomedics, Fujifilm, eFFECTOR Therapeutics, Merus, Nucana, Regeneron, Leap Therapeutics, Taiho Pharmaceuticals, EMD Serono, Daiichi Sankyo, ArQule, Syros Pharmaceuticals, Clovis Oncology, CytomX Therapeutics, InventisBio, Deciphera, Sermonix Pharmaceuticals, Zenith Epigentics, Arvinas, Harpoon, Black Diamond, Orinove, Molecular Templates, Seattle Genetics, Compugen, GI Therapeutics, Karyopharm Therapeutics, Dana-Farber Cancer Hospital, Shattuck Labs, PharmaMar, Olema Pharmaceuticals, Immunogen, Plexxikon, Amgen, Akesobio Australia, ADC Therapeutics, AtlasMedx, Aravive, Ellipses Pharma, Incyte, MabSpace Biosciences, ORIC Pharmaceuticals, Pieris Pharmaceuticals, Pieris Pharmaceuticals, Pionyr, Repetoire Immune Medicines, Treadwell Therapeutics, Accutar Biotech, Artios, Bliss Biopharmaceutical, Cascadian Therapeutics, Dantari, Duality Biologics, Elucida Oncology, Infinity Pharmaceuticals, Relay Therapeutics, Tolmar, Torque, BeiGene, Context Therapeutics, K-Group Beta, Kind Pharmaceuticals, Loxo Oncology, Oncothyreon, Orum Therapeutics, Prelude Therapeutics, Profound Bio, Cullinan Oncology, Bristol-Myers Squib, Eisai, Fochon Pharmaceuticals, Gilead Sciences, Inspirna, Myriad Genetics, Silverback Therapeutics, Stemline Therapeutics

Dr. Shaalan Beg and Dr. David Wang discuss key abstracts in GI cancers from the 2025 ASCO Gastrointestinal Cancers Symposium, including major advances in CRC, neoadjuvant approaches in esophageal cancer, and innovative studies on ctDNA. TRANSCRIPT Dr. Shaalan Beg: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Shaalan Beg. I'm a medical oncologist and an adjunct associate professor at UT Southwestern Medical Center in Dallas. Today, we're bringing you some key highlights from the 2025 ASCO Gastrointestinal Cancers Symposium, and I'm delighted to be joined by the chair of GI25, Dr. David Wang. Dr. Wang is a GI medical oncologist at the University of Michigan. Our full disclosures are available in the transcript of this episode.  Dr. Wang, thanks for coming on the podcast today. Dr. David Wang: Well, thank you. It's a pleasure to be here. Dr. Shaalan Beg: GI25 featured major therapeutic advances across the spectrum of GI malignancies, and it was exciting to hear about innovations and novel approaches that are shaping the future of our field. Before we start talking about specific abstracts, could you share some of your key highlights from the meeting? Dr. David Wang: Sure. Our theme this year was “Breaking Boundaries to Enhance Patient Centered Care.” Past years' themes have focused more on precision oncology, but we wanted to broaden our focus on patients and to be more holistic, which kind of led us into some of the Intersection [sessions] that we had. Each day started with a different Intersection. The first one was “Emerging Therapies in GI Cancers”, where invited speakers talked about bispecific antibody drug conjugates, theranostics, CAR T and other cell-based therapies. The second day was on “Personalized Risk Assessment for GI Cancers,” and this included looking at polygenic risk scores for colorectal cancer, microRNAs and liquid biopsies such as exosomes and pancreatic cancer and non-endoscopic screening modalities in esophageal cancer. And on our final day, we wanted to talk about “Integrative Oncology and Integrative Medicine,” looking at evidence-based uses of acupuncture and supplements in patients who are receiving treatment for cancer, mindfulness-based practices and exercise. And of course, we had a fantastic keynote talk by Dr. Pamela Kunz from the Yale School of Medicine titled, “Disrupting Gastrointestinal Oncology: Shattering Barriers with Inclusive Science.” She highlighted the intersection of science, patient care, and health and gender equity. And I would encourage your podcast listeners to access the lecture in ASCO's Meeting Library if they haven't yet had a chance to hear Dr. Kunz's wonderful lecture.  We were really happy this year because the attendance hit a new record. We had over 5,000 people attend either in person or virtually from their home or office, and we had almost 1,000 abstracts submitted to the meeting, so these were either record or near record numbers. We offered a lot of different networking opportunities throughout the meeting, and attending found these to be incredibly rewarding and important and this will continue to be an area of emphasis in future meetings. Dr. Shaalan Beg: Let's take a deeper dive into the exciting studies presented at GI25. The late breaking abstract LBA143 was CheckMate-8HW. This was the first results of NIVO + IPI versus NIVO monotherapy for MSI-high metastatic colorectal cancer. What are your thoughts about this study? Dr. David Wang: Yeah, so we know that colorectal cancer patients with MSI-high tumors don't necessarily respond well to chemotherapy. And we were fortunate because last year CheckMate-8HW actually looked at two different arms – so this was NIVO + IPI compared to standard of care chemotherapy and showed its very significant improvement in median progression-free survival. And that was actually published in the New England Journal of Medicine back in November of 2024. This year's presentation actually focused now on NIVO + IPI versus NIVO monotherapy. And as you know IPI+NIVO can be quite toxic. So this was an important analysis to be done. So we know that NIVO is definitely more easily tolerated. So what was interesting was that the 2-year and 3-year progression-free survival not surprisingly favored IPI+NIVO and this was statistically significant. And the overall response rate was also better with IPI+NIVO versus NIVO alone. I know we're always concerned about toxicities and there were higher grade 3 and 4 toxicity incidences in the combination arm versus the monotherapy arm, but overall, only about 28 additional events in several hundred patients treated. So I think that's well-tolerated. Our discussant Dr. Wells Messersmith actually said that, with this new data, he would consider doing combination immunotherapy in any patient that presented in the front line with MSI-high or deficient mismatch repair colorectal cancer that was metastatic. Dr. Shaalan Beg: One of the focuses for directing first-line therapy for colorectal cancer has been right and left sided colon cancer because we know these are two different cancers with their own unique molecular subtypes. We heard on Abstract 17, the DEEPER trial, the final analysis of modified FOLFOXIRI plus cetuximab versus bevacizumab for RAS wild-type and left sided metastatic colorectal cancer. How do you summarize the findings of this study and what should our readers be aware of? Dr. David Wang: Interestingly, this was a phase 2 study and the emphasis of the abstract was actually a subgroup analysis of those patients with RAS wild-type and BRAF wild-type as well as left sided cancers. So, I think the entire study enrolled 359 patients, but the analysis that was discussed at the meeting really focused on 178 patients that fit that characteristic. Very similar to what we've seen in prior studies, left-sided tumors have better response to cetuximab versus bevacizumab. And if you flip it so that you now are looking at right sided tumors, targeting EGFR is actually detrimental. The depth of response was better with cetuximab in these left sided RAS and BRAF mutant tumors. And so the lead author actually suggested that this could be a new first-line standard of care. And the question is, is there a benefit of doing this triple agent regimen with modified FOLFIRINOX? We know there's a lot more toxicity with that. Not clear that there's a benefit for that over FOLFOX, maybe in younger patients that could tolerate it. When our discussant, again Dr. Wells Messersmith, spoke about this, he said that, in his practice he would, again, favor cetuximab over bevacizumab in combination with chemo, these left-sided RAS and BRAF wild-type tumors, but that he would actually prefer a doublet versus a triplet chemo regimen, and that is consistent with the current NCCN guidelines. Dr. Shaalan Beg: Another area where colorectal cancer has been a wonderful model to study new technology has been in the area of circulating tumor DNA (ctDNA). And the BESPOKE CRC trial is looking to see if ctDNA can inform adjuvant treatment decisions for stage II and III colorectal cancer. And in Abstract 15, we heard final results of the BESPOKE CRC sub-cohort. What were the findings there? Dr. David Wang: BESPOKE CRC is another one of these important ctDNA studies. It was an observational study, not a randomized trial, but it did provide a lot of different insights to us. We know that there were over 1,700 patients enrolled, and so it was reported that this is the largest ctDNA study in colorectal cancer performed in the United States. And they were able to analyze over 1,100 patients.  Some of the key findings were that postoperative adjuvant therapy management decisions actually changed in 1 out of 6 patients, so that's pretty significant. In terms of surveillance, we know that patients who have ctDNA positivity, this is prognostic of recurrence. In terms of patients who have positive ctDNA post-surgery, it looked like, at least in this observational study, the majority of patients who received any benefit were those who had positive ctDNA. So adjuvant therapy, even in stage II and stage III patients seemed to only benefit those patients who have positive ctDNA. I think that does raise the question, and this also was brought up in the discussion, which is “Can we de-escalate adjuvant therapy in terms of patients who are ctDNA-negative post-op?” And Dr. Richard Kim from Moffitt felt that we are not yet there. Obviously, we need randomized control trials where we are taking ctDNA results and then randomizing patients to receive adjuvant or non-adjuvant to really know the difference.  Other questions that come up with use of ctDNA include: What do you do with these patients who turn positive? This study for BESPOKE actually followed patients out to two years after surgery. So what you do with a positive ctDNA result wasn't really clear. It seems to suggest that once you turn positive, patients go on to more intensive surveillance. You know, again as an observation, patients who did turn positive were able to go to metastasis-directed therapy much more quickly. And again, this was supposedly to improve their curative intent therapy. And I think the other question that has been brought up all the time is, is this really cost effective? Patients want to know, and we want to give patients that information, but I think we're still stuck with what to do with a positive ctDNA level in a patient that's on surveillance because no randomized control studies have actually suggested that we need to start systemic therapy right away. Dr. Shaalan Beg: Yeah. And I guess in terms of practice informing or practice changing, these results may not give us a clear answer. But because a lot of patients are asking for these tests, it does give us some real world experiences on what to expect in terms of conversion of these positive into negative and the outcome so we can have a shared decision making with our patients in the clinic and then come up with a determination on whether ctDNA for molecular residual disease is something which would be worthwhile for the care of our patient. But more to come, I guess, in coming years to answer different problems around this challenge. Dr. David Wang: Yes, I agree. Dr. Shaalan Beg: The BREAKWATER trial looked at the use of encorafenib, cetuximab and chemotherapy for BRAF V600E-mutant metastatic colorectal cancer. We've covered this combination for a second- third-line treatment in metastatic colorectal cancer previously. Abstract 16 from GI25 was evaluating the use of this regimen in the first-line space. Everyone was looking forward to these results, and what did the investigators present? Dr. David Wang: I think this is, as you mentioned, a nice follow up to later lines of therapy where Dr. Kopetz from MD Anderson pioneered use of encorafenib, cetuximab and binimetinib in the BEACON trial. Everybody was kind of curious what would happen now if you use encorafenib plus cetuximab plus chemotherapy in the first-line setting. And so this is an interim analysis that was pre-planned in the phase 3 open label BREAKWATER trial. And even though there were three arms, and so the three arms were encorafenib plus cetuximab, encorafenib plus cetuximab plus FOLFOX, or standard of care chemo, only two arms were presented in the abstract. So basically looking at encorafenib plus cetuximab and FOLFOX-6 versus standard of care therapy, and the overall response rate was statistically significant with a 60.9% overall response rate encorafenib plus cetuximab plus chemo arm versus standard of care chemo was only 40%. The interim overall survival also was different. It was 92% versus 87% at 6 months and 79% versus 66% at 12 months, again favoring the chemotherapy plus encorafenib plus cetuximab. In terms of the statistics, the p was 0.0004. However, the pre-plan analysis required the p-value to be 1x10 to the -8. And so even though this looks really good, it hasn't quite met its pre-specified significance level. The good thing is that this is only interim analysis and the study is ongoing with future analysis planned.  So the real question is: Does it matter when we actually use this regimen? We know that the regimen's approved in the second third-line setting. What about in the first line? And there was some preclinical data that the discussant reviewed that shows that patients actually benefit if this is done in the first-line setting. For example, there was some preclinical data showing that even FOLFIRI, for example, can upregulate RAS, which would make tumors more resistant to this combination. This was thought to be practice-changing in a patient that has B600E showing up treatment naive that we should probably consider this regimen. And actually this did receive accelerated FDA approval about a month ago. Dr. Shaalan Beg: Yeah, and for what it's worth, I put up a Twitter poll asking my Twitter followers on how the BREAKWATER trial results will change their approach for newly diagnosed BRAF mutated colorectal cancer. We got 112 responses; 72% said that they will incorporate encorafenib, cetuximab, FOLFOX for their frontline BRAF mutated patients. But 23% said that they would like to wait for overall survival results. Dr. David Wang: Wow, that's interesting. They really want that 1x10 to the -8. Dr. Shaalan Beg: I guess so. All right. Let's change gears and talk about esophageal cancer. LBA329 was the SCIENCE study which presented preliminary results from a randomized phase 3 trial comparing sintilimab and chemoradiotherapy plus sintilimab versus chemoradiotherapy for neoadjuvant resectable locally advanced squamous esophageal cancer. Where are we in this space? Dr. David Wang: Okay. So, yeah, this was an interesting trial. Again, just to set the context, esophageal squamous cell carcinoma is more prevalent in Asia. And the study sites as well as the patients were mostly from Asia. So this was again a phase 3 trial with interim results. They only rolled 146 out of the planned 420 for this interim analysis. And yeah, they're using immune checkpoint inhibitor that we don't use in the United States, sintilimab, combined with their two standards of neoadjuvant therapy, either chemotherapy, which is more common in Asia, or or chemoradiation, which is more common in the US and Western Europe, versus chemoradiation. And so they actually had two primary endpoints, but only were reporting one. So their two primary endpoints were pathCR and the other one was event-free survival. The event-free survival, again, was not reported at the meeting.  What they found was that in terms of pathCR rate, if you take the two arms that are really informative about that, chemoradiation plus sintilimab versus chemoradiation alone, the pathCR rate was 60% versus 47%. We know that chemo alone doesn't induce as much of a pathCR rate, and that was 13%. So it was found that the delta in terms of pathCR between the chemoradiation arms, one with sintilimab and one without, was significant. And this actually confirms data again from Asia, like for the ESCORT-NEO trial where it used another immune checkpoint inhibitor pembrolizumab in addition to neoadjuvant chemo.  So as our discussant for this abstract said, yes, we know that radiation combined with chemotherapy improves pathCR rates, but we have recent data from the ESOPEC trial, we don't know that that necessarily will translate to overall survival. So again, waiting for additional enrollments and longer term follow up before incorporating this into clinical care here. Dr. Shaalan Beg: So David, how do the results of the SCIENCE trial compare with our practice in the United States and ongoing studies asking questions for neoadjuvant therapy for esophageal carcinoma in the United States? Dr. David Wang: I think obviously immune checkpoint inhibitor in the new adjuvant setting is important. Jennifer Eads at UPenn is running that EA2174 which is looking at chemoradiation plus or minus nivolumab, and then in non-pathCR responders randomized to adjuvant nivolumab per CheckMate 577 or nivolumab with intensification adding ipilimumab. We know that the ESOPEC trial just came out, and was published actually during the meeting, and that really focuses on adenocarcinomas. So adenocarcinomas of the GE junction, distal esophagus, now, we would probably treat very similarly to gastric using perioperative FLOT. However, the standard in the US for esophageal squamous cell carcinoma remains neoadjuvant chemoradiation. We know that squamous cell carcinomas are more exquisitely sensitive to radiotherapy. And then obviously in those patients who don't achieve a pathologic complete response, the expectation would be that they would go on to receive nivolumab per CheckMate 577. Again, the thought is that these tumors are more sensitive to immunotherapy given their higher incidences of mutational changes. And so again, this kind of goes along with the positive results seen in the SCIENCE trial that we just discussed with sintilimab but also EFFECT-neo with pembrolizumab. Obviously, we await the results of Jennifer's trial. Dr. Shaalan Beg: And the last abstract I was hoping we could get your perspective on was Abstract 652, which is a Phase 3 study of everolimus plus lanreotide versus everolimus monotherapy for unresectable or recurrent gastroenteropancreatic neuroendocrine tumors, the STARTER-NET trial. What were the results of this study? Dr. David Wang: So, I just want to give a shout out because we did have a session at this year's GI ASCO that looked at more rare tumors. So appendiceal tumors, neuroendocrine tumors, those kinds of things. So again, I would encourage your listeners to listen to that session if they have interest in that. Another type of rare tumor was adenosquamous tumors.  But in terms of the STARTER-NET trial, this was again an interim analysis of his phase 3trial and it was looking at combining everolimus plus lanreotide versus everolimus. So we know that in pancreatic-gastric neuroendocrine tumors, if you have low Ki-67, a well differentiated tumor, that the standard of care really is a somatostatin analog, and sometimes if they're more aggressive, we kind of consider molecular targeted therapy with everolimus. This was asking the question of whether we should do the combination on the frontline. And what was interesting is in this study, the patients were actually more of a poor prognostic set. So they had Ki-67 up to 20% or these were patients that actually had multiple liver lesions. And what they found was a median for progression free survival was improved with a combination out to 29.7 months versus 11.5 months with the somatostatin analog alone, and that the overall response rate was 23% versus 8.3%, again, favoring the combination. If you looked at subgroup analysis, it was actually those patients who had Ki-67 greater than 10%, so the more aggressive tumors, or those with diffuse liver lesions that had the most benefit. So I think that would be the patient population I would consider this new combination with using would be those patients again with poorer prognosis neuroendocrine tumor phenotype. Dr. Shaalan Beg: Thank you very much, Dr. Wang, for sharing your insights with us today and your great work to build a robust GI Cancers Symposium this year. Dr. David Wang: Well, thank you. I mean that really is a cooperative effort. We appreciate all the members of the GI25 Program Committee as well as the ASCO staff that just made it an outstanding 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 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. Shaalan Beg @ShaalanBeg  Dr. David Wang Follow ASCO on social media:   @ASCO on Twitter  @ASCO on BlueSky 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. David Wang: Honoraria:  Novartis Consulting or Advisory Role: Novartis, Cardinal Health, Bristol-Myers Squibb, BeiGene, Eisai  

The Flu Vaccine: Science at its Worst   Richard Gale and Gary Null Progressive Radio Network, December 20, 2024   Joshua Hadfield was a normal, healthy developing child as a toddler. In the midst of the H1N1 swine flu frenzy and the media fear mongering about the horrible consequences children face if left unvaccinated, the Hadfield family had Joshua vaccinated with Glaxo's Pandermrix influenza vaccine.  Within weeks, Joshua could barely wake up, sleeping up to nineteen hours a day. Laughter would trigger seizures. Joshua was diagnosed with narcolepsy, “an incurable, debilitating condition” associated with acute brain damage.[1]  Looking back, Pandermrix was a horrible vaccine.  Research indicates that it was associated with a 1400% increase in narcolepsy risk. A medical team at Finland's National Institute for Health and Welfare recorded 800 cases of narcolepsy associated with this vaccine.  Aside from the engineered viral antigens, the other vaccine ingredients are most often found to be the primary culprits to adverse vaccine reactions. The Finnish research, on the other hand, indicated that the vaccine's altered viral nucleotide likely contributed to the sudden rise in sleeping sickness.[2] Although Pandermrix was pulled from the market for its association with narcolepsy and cataplexy (sudden muscle weakness), particularly in children, it should never have been approved and released in the first place.  The regulatory fast tracking of the HINI flu vaccines is a classic, and now common, example of regulatory negligence by nations' health officials. The failure of proper regulatory evaluation and oversight resulted in Joshua and over 1,000 other people becoming disabled for life. Settlements to cover lawsuits exceeded 63 million pounds in the UK alone.  No one should feel complacent and assume flu vaccine risks only affect young children. Sarah Behie was 20 years old after receiving a flu shot.  Three weeks later her health deteriorated dramatically. Diagnosed with Guillain-Barre syndrome, a not uncommon adverse effect of influenza vaccination, four years later Sarah remains paralyzed from the waist down, incapable of dressing and feeding herself, and rotting away in hospitals and nursing homes.[3]  Flu vaccines are perhaps the most ineffective vaccine on the market.  Repeatedly we are told by health officials that the moral argument for its continued use is for “the greater good,” although this imaginary good has never been defined scientifically. Year to year, how effective any given seasonal flu vaccine will be is a throw of the dice. Annual flu vaccine efficacy rates in the US have demonstrated significant variability. Data from the CDC reveal efficacy estimates of approximately 39% for the 2020–2021 season, 37% for 2021–2022, 52% for 2022–2023, and a preliminary estimate of 50% for the 2023–2024 season.  Preliminary CDC estimates for this flu season estimates 34% likely efficacy. Although these are CDC's figures, independent figures are consistently much lower. At their best, flu vaccines in recent years are around 50% effective according to official health analysis. During some seasons, vaccine efficacy is a bust. For example, the 2014-2015 flu season strain match was such a failure that the CDC warned the American public that the vaccine was only 23% effective.[4]  Nevertheless, these rates underscore the vaccine's inconsistent protection. Studies such as those by Skowronski and Belongia further highlight flu vaccines' variability and force to question whether the vaccine is capable of providing any reliable protection.[5,6] Moreover, Cochrane Collaboration reviews, known for their rigorous analyses, consistently find that flu vaccines reduce influenza-like illness by only about 1% in healthy adults and have negligible impact on hospitalizations and mortality rates. This limited efficacy raises critical concerns about the vaccine's utility, particularly when weighed against its risks.  Perhaps the most useless flu vaccine that should have never been approved was Medimmune's live attenuated flu vaccine (LAIV) FluMist, which the CDC later had removed from the market because it was found to so ineffective—only 3 percent according to an NBC report.[6] However the real reason may be more dire, and this a fundamental problem of all live and attenuated vaccines: these vaccines have been shown to “shed” and infect people in contact with the vaccinated persons, especially those with compromised immune systems.  Consequently, both the unvaccinated and the vaccinated are at risk.  The CDC acknowledges this risk and warns “Persons who care for severely immunosuppressed persons who require a protective environment should not receive LAIV, or should avoid contact with such persons for 7 days after receipt, given the theoretical risk for transmission of the live attenuated vaccine virus.”[7]  According to the FDA's literature on FluMist, the vaccine was not studied for immunocompromised individuals (yet was still administered to them), and has been associated with acute allergic reactions, asthma, Guillain-Barre, and a high rate of hospitalizations among children under 24 months – largely due to upper respiratory tract infections.  Other adverse effects include pericarditis, congenital and genetic disorders, mitochondrial encephalomyopathy or Leigh Syndrome, meningitis, and others.[8]  The development and promotion of the influenza vaccine was never completely about protecting the public. It has been the least popular vaccine in the US, including among healthcare workers. Rather, similar to the mumps vaccine in the MMR, it has been the cash cow for vaccine makers.  Determining the actual severity of any given flu season is burdened by federal intentional confusion to mislead the public.  The CDC's first line of propaganda defense to enforce flu vaccinations is to exaggerate flu infections as the cause of preventable deaths.   However, validating this claim is near impossible because the CDC does not differentiate deaths caused by influenza infection and deaths due to pneumonia.  On its website, the CDC lumps flu and pneumonia deaths together, currently estimated at 51,000 per year. The large majority of these were pneumonia deaths of elderly patients. Yet in any given year, only 3-18% of suspected influenza infections actually test positive for a Type A or B influenza strain.[9]  As an aside, it is worth noting that during the first two years of the COVID-19 pandemic, an extraordinary and unprecedented phenomenon occurred: influenza infections, which have long been a seasonal health challenge, seemingly disappeared. Federal health agencies such as the CDC attributed this sharp decline in flu cases to the implementation of non-pharmaceutical interventions (NPIs) like mask-wearing, social distancing, and widespread lockdowns. However, this explanation raises critical questions about its plausibility. If these measures were effective enough to virtually eliminate influenza, why did they not similarly prevent the widespread transmission of SARS-CoV-2? This contradiction highlights the need to critically examine the possible explanations behind the anomaly, questioning whether the disappearance of the flu was truly a result of public health measures or due to other factors such as diagnostic practices, viral interference, and disruptions to seasonal flu patterns. If these interventions were indeed effective, their impact should not have been so starkly selective between two similarly transmitted viruses. This contradiction undermines the plausibility of attributing the disappearance of flu cases solely to NPIs. A more plausible explanation for the disappearance of flu cases lies in the diagnostic focus on SARS-CoV-2 during the pandemic. Individuals presenting with flu-like symptoms were overwhelmingly diagnosed for COVID-19 with faulty PCR testing methods rather than influenza, as public health resources were directed toward managing the pandemic. This prioritization inevitably led to a significant underreporting of flu cases. Furthermore, the symptoms of influenza and COVID-19 overlap significantly, including fever, cough, and fatigue. In the absence of influenza testing, many flu cases were wrongly diagnosed as COVID-19, further inflating SARS-CoV-2 case numbers while contributing to the perceived disappearance of the flu.  One of the more controversial findings in recent flu vaccine research involves the phenomenon of viral interference, wherein vaccinated individuals may become more susceptible to other respiratory pathogens. To date there is only one gold standard clinical trial with the flu vaccine that compares vaccinated vs. unvaccinated, and it is not good news for the CDC, the vaccine makers, and the push to booster everyone with the Covid-19 mRNA vaccines. This Hong Kong funded double-blind placebo controlled study followed the health conditions of vaccinated and unvaccinated children between the ages of 6-15 years for 272 days. The trial concluded the flu vaccine holds no health benefits. In fact, those vaccinated with the flu virus were observed to have a 550% higher risk of contracting non-flu virus respiratory infections. Among the vaccinated children, there were 116 flu cases compared to 88 among the unvaccinated; there were 487 other non-influenza virus infections, including coronavirus, rhinovirus, coxsackie, and others, among the vaccinated versus 88 with the unvaccinated.[10]  This single study alone poses a scientifically sound warning and rationale to avoid flu vaccines at all costs. It raises a further question: how many Covid-19 cases could be directly attributed to weakened immune systems because of prior flu vaccination? A 2019 study conducted by the US Armed Forces investigated the relationship between influenza vaccination and susceptibility to other respiratory infections, including coronaviruses. Analyzing data from over 9,000 individuals, the researchers found that people who received the flu vaccine were more likely to test positive for certain non-influenza respiratory viruses. Notably, influenza vaccination was associated with an increased likelihood of contracting coronaviruses and human metapneumovirus.[11] These findings suggest a complex interaction between influenza vaccination and susceptibility to different respiratory pathogens, and challenges the belief that flu vaccines provide greater benefits over risks. The same researchers' follow up study in in 2020 furthermore concluded that “vaccine derived virus interference was significantly associated with coronavirus and human metapneumovirus.[12] Additional recent studies, such as those by Bodewes, which identified immune interference due to repeated annual flu vaccinations,[13] and Shinjoh, which highlighted increased viral interference in vaccinated children, provide further evidence of this relationship.[14] These findings challenge the prevailing assumption that flu vaccination has only positive effects on immune health and raise important questions about the broader implications of repeated annual vaccination. In a follow up study after the H1N1 swine flu scare, Canadian researcher Dr. Danuta Skowronski noted that individuals with a history of receiving consecutive seasonal flu shots over several years had an increased risk of becoming infected with H1N1 swine flu.  Skowronski commented on the findings, “policy makers have not yet had a chance to fully digest them [the study's conclusions] or understand the implications.”  He continued, “Who knows, frankly? The wise man knows he knows nothing when it comes to influenza, so you always have to be cautious in speculating.”[15] There is strong evidence suggesting that all vaccine clinical trials carried out by manufacturers fall short of demonstrating vaccine efficacy accurately. And when they are shown to be efficacious, it is frequently in the short term and offer only partial or temporary protection. According to an article in the peer-reviewed Journal of Infectious Diseases, the only way to evaluate vaccines is to scrutinize the epidemiological data obtained from real-life conditions. In other words, researchers simply cannot -- or will not -- adequately test a vaccine's effectiveness and immunogenicity prior to its release onto an unsuspecting public.[16] According to Dr. Tom Jefferson, who formerly led the Cochrane Collaboration's vaccine analyses, it makes little sense to keep vaccinating against seasonal influenza based on the evidence.[17] Jefferson has also endorsed more cost-effective and scientifically-proven means of minimizing the transmission of flu, including regular hand washing and wearing masks. There is also substantial peer-reviewed literature supporting the supplementation of Vitamin D.  Dr. Jefferson's conclusions are backed by former Johns Hopkins University School of Medicine scientist Peter Doshi, PhD, in the British Journal of Medicine. In his article Doshi questions the flu vaccine paradigm stating:  “Closer examination of influenza vaccine policies shows that although proponents employ the rhetoric of science, the studies underlying the policy are often of low quality, and do not substantiate officials' claims. The vaccine might be less beneficial and less safe than has been claimed, and the threat of influenza appears overstated.”[18]         A significant body of research proves that receiving the flu shot does not reduce mortality among seniors.[19] One particularly compelling study was carried out by scientists at the federal National Institutes of Health (NIH) and published in the Journal of the American Medical Association (JAMA). Not only did the study indicate that the flu vaccine did nothing to prevent deaths from influenza among seniors, but that flu mortality rates increased as a greater percentage of seniors received the shot.[20] Dr. Sherri Tenpenny reviewed the Cochrane Database reviews on the flu vaccine's efficacy. In a review of 51 studies involving over 294,000 children, there was “no evidence that injecting children 6-24 months of age with a flu shot was any more effective than placebo. In children over 2 years of age, flu vaccine effectiveness was 33 percent of the time preventing flu. In children with asthma, inactivated flu vaccines did not prevent influenza related hospitalizations in children. The database shows that children who received the flu vaccine were at a higher risk of hospitalization than children who did not receive the vaccine.[21]  In a separate study involving 400 asthmatic children receiving a flu vaccine and 400 who were not immunized, there was no difference in the number of clinic and emergency room visits and hospitalizations between the two groups.[22]  In 64 studies involving 66,000 adults, “Vaccination of healthy adults only reduced risk of influenza by 6 percent and reduced the number of missed work days by less than one day. There was a change in the number of hospitalizations compared to the non-vaccinated. In further studies of elderly adults residing in nursing homes over the course of several flu seasons, flu vaccinations were insignificant for preventing infection.[23] Today, the most extreme wing of the pro-vaccine community continue to diligently pursue mandatory vaccination across all 50 states.  During the flu season, the debate over mandatory vaccination becomes most heated as medical facilities and government departments attempt to threaten employees and schools who refuse vaccination. Although this is deeply worrisome to those who advocate their Constitutional rights to freedom of choice in their healthcare, there are respectable groups opposing mandatory flu shots.  The Association of American Physicians and Surgeons “objects strenuously to any coercion of healthcare personnel to receive influenza immunization. It is a fundamental human right not to be subjected to medical interventions without fully informed consent.”  The good news is that the majority of Americans have lost confidence in the CDC after the agency's dismal handling of the Covid-19 pandemic. Positive endorsement of the CDC would plummet further if the public knew the full extent of CDC officials lying to Congress and their conspiracy to commit medical fraud for two decades to cover=up evidence of an autism-vaccine association.  When considering the totality of evidence, the benefit-risk ratio of flu vaccination becomes increasingly problematic. The poor and inconsistent efficacy rates, combined with the potential for serious adverse reactions and the phenomenon of viral interference, clearly indicates that the vaccine does not deliver the public health benefits it promises. Public health strategies must balance the benefits of vaccination against its risks, particularly for vulnerable populations such as children and pregnant women.  Imagine the tens of thousands of children and families who would have been saved from life-long neurological damage and immeasurable suffering if the CDC was not indebted to protecting the pharmaceutical industry's toxic products and was in fact serving Americans' health and well-being? One step that can be taken to begin dismantling the marriage between the federal health agencies and drug companies is to simply refuse the flu vaccine and protect ourselves by adopting a healthier lifestyle during the flu season.    NOTES [1] http://yournewswire.com/boy-awarded-174000-after-flu-vaccine-causes-permanent-brain-damage/  [2]  http://www.globalresearch.ca/finnish-scientists-identify-link-between-glaxosmithklines-swine-flu-vaccine-pandemrix-and-narcolepsy/5423154 [3] http://sharylattkisson.com/woman-paralyzed-after-flu-shot-receives-11-million-for-treatment/ [4]  http://america.aljazeera.com/articles/2014/12/3/flu-vaccine-ineffective.html  [5]Skowronski DM, Leir S, et al. Influenza vaccine effectiveness by A (H3N2) phylogenetic subcluster and prior vaccination history: 2016–2017 and 2017–2018 epidemics in Canada. J Infectious Diseases, 2021; 225(8), 1387–1397. [6] Belongia EA, Skowronski DM, et al. Repeated annual influenza vaccination and vaccine effectiveness: review of evidence. Expert Review of Vaccines, 2023; 16(7), 743–759. [7]  Barbara Lo Fisher, The Emerging Risks of Live Virus and Virus Vectored Vaccines.  National Vaccine Information Center, 2014  [8]  http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM294307.pdf  [9] Barbara Lo Fisher, “CDC Admits Flu Shots Fail Half the Time.”  NVIC, October 19, 2016 [10] http://gaia-health.com/gaia-blog/2013-06-02/flu-vax-causes-5-5-times-more-respiratory-infections/  [11] Wolff GG. Influenza vaccination and respiratory virus interference among Department of Defense personnel during the 2017–2018 influenza season. Vaccine. 2019 Oct 10;38(2):350–354.   [12] Wolff GG. (2020). Influenza vaccination and respiratory virus interference among Department of Defense personnel. Vaccine, 2020 38(2), 350-354.  [13] Bodwes F, Janssens Y, et al. The role of cell-mediated immunity against influenza and its implications for vaccine evaluation. Frontiers in Immunology, 2021 13, 959379. DOI: 10.3389/fimmu.2022.959379  [14] Sinojoh M, Sugaya N, et al. Effectiveness of inactivated influenza and COVID-19 vaccines in hospitalized children in the 2022/23 season in Japan: The first season of co-circulation of influenza and COVID-19. Vaccine, 2022; 41(1), 100-107.  [15]  http://www.cbc.ca/news/health/flu-shot-linked-to-higher-incidence-of-flu-in-pandemic-year-1.1287363 [16]   Weinberg GA, Szilagyi PG. Vaccine Epidemiology: Efficacy, Effectiveness, and the Translational Research Roadmap. J Infect Dis 20210;201.1: 1607-610.  [17] ‘A Whole Industry Is Waiting For A Pandemic', Der Spiegel, http://www.spiegel.de/international/world/0,1518,637119-2,00.html, [18] Dolshi P. "Influenza: Marketing Vaccine by Marketing Disease." BMJ 2013;346: F3037.  [19] Simonsen L, Reichert T, et al. . Impact of Influenza Vaccination on Seasonal Mortality in the US Elderly Population. Arch Intern Med Archives 2005;165(3): 265.  [20] Glezen WP, Simonsen L. Commentary: Benefits of Influenza Vaccine in US Elderly--new Studies Raise Questions. Internat J Epidemiology2006;35(2): 352-53. [21] 105th International Conference of the American Thoracic Sociey, May 15-20, 2009 (quoted in , Sherri Tenpenny.  “The Truth about Flu Shots”.  Idaho Observer, June 1, 2009)  [22] ibid  [23] Ibid.

Dr. Allison Zibelli and Dr. Erika Hamilton discuss the results of the DESTINY-Breast06 trial in HR+, HER2-low and HER2-ultralow metastatic breast cancer and the A-BRAVE trial in early triple-negative breast cancer, the results of which were both presented at the 2024 ASCO Annual Meeting. TRANSCRIPT Dr. Allison Zibelli: Hello, I'm Dr. Allison Zibelli, your guest host of the ASCO Daily News Podcast. I'm an associate professor of medicine and breast medical oncologist at the Sidney Kimmel Cancer Center of Jefferson Health in Philadelphia. My guest today is Dr. Erika Hamilton, a medical oncologist and director of breast cancer research at the Sarah Cannon Research Institute. We'll be discussing the DESTINY-Breast06 trial, which showed a progression-free advantage with the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) compared to chemotherapy in hormone receptor-positive HER2-low or HER2-ultralow metastatic breast cancer. We'll address the implications of this study for the community, including the importance of expanding pathology assessments to include all established subgroups with HER2 expression, and the promise of expanding eligibility for antibody-drug conjugates. We'll also highlight advances in triple-negative breast cancer, focusing on the A-BRAVE trial, the first study reporting data on an immune checkpoint inhibitor avelumab in patients with triple-negative breast cancer with invasive residual disease after neoadjuvant chemotherapy.  Our full disclosures are available in the transcript of this episode.  Erika, it's great to have you on the podcast today. Dr. Erika Hamilton: Thanks so much, Allison. Happy to join. Dr. Allison Zibelli: Antibody-drug conjugates are rapidly changing the treatment landscape in breast cancer. The data from the DESTINY-Breast06 trial suggests that trastuzumab deruxtecan may become a preferred first-line treatment option for most patients with HER2-low or HER2-ultralow metastatic breast cancer after progression on endocrine therapy. First, could you remind our listeners, what's the definition of HER2-ultralow and what were the findings of this trial? Dr. Erika Hamilton: Yeah, those are fantastic questions. Ultralow really has never been talked about before. Ultralow is part of a subset of the IHC zeros. So it's those patients that have HER2-tumor staining that's less than 10% and incomplete but isn't absolutely zero. It's even below that +1 or +2 IHC that we have classified as HER2-low. Now, I think what's important to remember about D-B06, if you recall, D-B04 (DESTINY-Breast04) was our trial looking at HER2-low, is that D-B06 now included HER2-low as well as this HER2-ultralow category that you asked about. And it also moved trastuzumab deruxtecan up into the frontline. If you recall, D-B04 was after 1 line of cytotoxic therapy. So now this is really after exhausting endocrine therapy before patients have received other chemotherapy. And what we saw was an improvement in progression-free survival that was pretty significant: 13.2 months versus 8.1 months, it was a hazard ratio of 0.62. And you can ask yourself, “well, was it mainly those HER2-low patients that kind of drove that benefit? What about the ultralow category?” And when we look at ultralow, it was no different: 13.2 months versus 8.3 months, hazard ratio, again, highly significant. So I think it's really encouraging data and gives us some information about using this drug earlier for our patients with hormone receptor-positive but HER2-negative disease.  Dr. Allison Zibelli: I thought this study was really interesting because it's a patient population that I find very difficult to treat, the hormone receptor-positive metastatic patient that's not responding to endocrine therapy anymore. But it's important to mention that T-DXd resulted in more serious toxicities compared to traditional chemotherapy in this study. So how do you choose which patients to offer this to? Dr. Erika Hamilton: Yeah, those are both great points. So you're right, this is after endocrine therapy. And in fact, about 85% of these patients had received at least 2 prior lines of endocrine therapy. So I have some people kind of asking, “Well, if endocrine therapy really isn't benefiting everyone in the second-line setting post-CDK, should we just move to the ADCs?” And, no, probably we should really make sure that we're exhausting endocrine therapies for those patients that are going to benefit. And once we determine somebody has endocrine-resistant disease, that's when we would think about switching. In terms of the side effects, I think you're right. It's mainly ILD that's probably the more serious side effect that we worry about a little bit with trastuzumab deruxtecan. The good news is, through multiple trials, we've gotten a little bit better at managing this. We've pretty much all but eliminated any fatal cases of ILD, definitely less than 1% now. ILD rates, depending on what study you look for, kind of ranges in that 10% to 15% range. Any grade ILD on D-B06 was 11.3%. So really kind of making sure that we look for ILD at scans, making sure that patients are educated to tell us about any new pulmonary symptoms: cough, exertional dyspnea, shortness of breath at rest, etc. But I think the most common side effects that we really deal with on a daily basis with trastuzumab deruxtecan, luckily, is nausea, which we've gotten better at managing with the 2- or 3-drug antiemetic regimen, and probably a little bit of fatigue as well. Dr. Allison Zibelli: Thank you. So, I think for most people in the community, the sticking point here will be expanding pathology assessments to include all of the subgroups, including the ultralow. Most patients in the community are not testing for HER2-low and HER2-ultralow now. Dr. Erika Hamilton: Historically, we kind of all did HER2 IHC, right? And then as FISH became available, there were a lot of institutions that moved to FISH and maybe didn't have IHC anymore. And now, at least in my institution, we do both. But I think it's a very important point that you made that IHC was really designed to pick out those patients that have HER2-high, the 3 pluses or the FISH amplified cases. It was not to tell the difference between a 1+ or a 2+ or a 0 that's not quite a 0 and a 1+. So I think you're right. I think this is tough. I probably have a little bit more of an interesting take on this than some people will. But data from ASCO, not this year but in 2023, there was actually a pretty eloquent study presented where they looked at serial biopsies in patients, and essentially, if you got up to 4 or 5 biopsies, you were guaranteed to have a HER2-low result. Now, this didn't even include ultralow, which is even easier. If we know we include ultralow, we're really talking about probably 85% to 90% of our patients now that have some HER2 expression. But if we biopsy enough, we're guaranteed to get a HER2 low.  And so I think the question really is, if we know IHC wasn't really designed to pick out these ultralows, and we know kind of greater than 90% of patients are going to have some expression, did we kind of develop this drug a little bit backwards? Because we thought we understood HER2, and the reality is this drug is a little bit more like a sacituzumab govitecan, where we don't test for the TROP2. Should we really be kind of serial biopsying these patients or should maybe most patients have access to at least trying this drug?  Dr. Allison Zibelli: So I don't think that most of my patients will really be happy to sign up for serial biopsies. Dr. Erika Hamilton: Agreed. Dr. Allison Zibelli: Do we have any emerging technologies for detecting low levels of HER2? You talked about how the IHC test isn't really designed to detect low levels of HER2. Do you think newer detection techniques such as immunofluorescence will make a difference, or will we have liquid biopsy testing for this? Dr. Erika Hamilton: Yeah, I think liquid biopsy may be a little bit hard, just because some of those circulating tumor cells are more of a mesenchymal-type phenotype and don't necessarily express all of the same receptors. Normally, if they're cytokeratin-positive, they do, but certainly there is a lot out there looking at more sensitive measures. You mentioned immunofluorescence, there are some even more quantitative measures looking at lower levels of HER2. I definitely think there will be. I guess, ultimately, with even the IHC zeros that are the less than 10% incomplete staining, having a PFS that was absolutely no different than the HER2 low, I guess the question is, how low can we really go? We know that even the IHC zeros doesn't mean that there's no HER2 expression on the cell surface. It just means that maybe there's a couple of thousand as opposed to 10,000 or 100,000 copies of HER2. And so it really appears that perhaps this drug really is wedded to having a lot of HER2 expression. So ultimately, I wonder how much we're going to have to use those tests, especially with what we know about tumor heterogeneity. We know that if we biopsy 1 lesion in the liver, biopsy a lymph node, or even another lesion in the liver, that the HER2 results can have some heterogeneity. And so ultimately, my guess is that most people have some HER2 expression on their breast cancer cells. Dr. Allison Zibelli: So maybe we're going to be using this for everybody in the future. Dr. Erika Hamilton: It certainly seems like we keep peeling back the onion and including more and more patients into the category that are eligible to receive this. I agree. Dr. Allison Zibelli: Let's move on to triple-negative breast cancer, namely the A-BRAVE trial. This was an interesting trial for patients that did not get neoadjuvant immunotherapy and testing 2 groups. The first group was those with residual disease after neoadjuvant conventional chemotherapy. The second group was people with high-risk disease identified upfront that had upfront surgery. The study found that adjuvant avelumab did not improve disease-free survival versus observation, which was the study's primary endpoint. But interestingly, there was a significant improvement in 3-year overall survival and distant disease-free survival. Can you give us your thoughts on that? Dr. Erika Hamilton: Yeah, I think this study was really interesting. Right now, the standard for our patients with larger or node-positive triple-negative cancers is KEYNOTE-522. It's a pretty tough regimen. It's kind of 2 sequential uses of 2 chemotherapies, so 4 chemotherapy agents total with pembrolizumab. But you're right, this study looked at those that had residual disease after neoadjuvant that didn't include immunotherapy, or those patients that didn't get neoadjuvant therapy, went to surgery, and then were receiving chemotherapy on the back end. I'm going to give you the numbers, because you're right. The 3-year disease-free survival rates were not statistically significant. It was 68.3% among those that had avelumab, 63.2% with those that had observation only. So the difference was 5.1% in favor of avelumab, but it wasn't statistically significant. A p value of 0.1, essentially. But when we looked at the 3-year overall survival rates, we saw the same pattern, those patients with the avelumab doing better, but it was 84.8% overall survival and not, unfortunately, dying, versus 76.3%. So the magnitude of benefit there was 8.5%, so about 3% higher than we saw for disease-free survival, and this was statistically significant.  So is this going to change practice for most patients? I probably don't think so. I think for our patients that have larger tumors that's recognized upfront or have node positivity, we're probably going to want to use neoadjuvant chemo. Being able to get a PCR is very prognostic for our patients and enables us to offer things on the back end, such as PARP inhibitors or further chemotherapy of a different type of chemotherapy. But for our patients that go to surgery and maybe the extent of their disease just isn't recognized initially, this could be an option. Dr. Allison Zibelli: I agree. I think this will be a really useful regimen for patients where we get the surprise lymph node that we weren't expecting, or somebody who comes to us, maybe without seeing the medical oncologist, who got upfront surgery. So I thought this was really interesting. What kind of translational studies do you think we're going to do to try and understand which patients would benefit from avelumab? Dr. Erika Hamilton: Yeah, I think that's a great question, and honestly, it's a question that we haven't really answered in the neoadjuvant setting either. Immunotherapy in breast cancer is just a little bit different than it is in some other diseases. We have a benefit for those patients that are PD-L1 positive in the first line. We really haven't seen benefit for metastatic outside of first line. And then in neoadjuvant, it was among all comers. We don't have to test for PD-L1. And now we have this avelumab data from A-BRAVE. I think the question is, is there's probably a subset of patients that are really getting benefit and a subset that aren't. And I don't know that PD-L1 testing is the right test. We know a lot of people are looking at TILs, so kind of lymphocytes that are infiltrating the tumor, a variety of other kind of immunologic markers. But my guess is that eventually we're going to get smart enough to tease out who actually needs the immunotherapy versus who isn't going to benefit. But we're not quite there yet. Dr. Allison Zibelli: Thank you, Erika, for sharing your valuable insights with us on the ASCO Daily News Podcast today. Dr. Erika Hamilton: Thanks so much for having me.  Dr. Allison Zibelli: And thank you to our listeners for joining us. You'll find the links to all the abstracts discussed today in the transcript of this episode. Finally, if you like this podcast and you value our insights, please take a moment to rate, review, and subscribe wherever you get your podcasts. It really helps other people to find us. So thank you very much for listening today.   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. Allison Zibelli Dr. Erika Hamilton @ErikaHamilton9   Follow ASCO on social media:  @ASCO on Twitter    ASCO on Facebook    ASCO on LinkedIn      Disclosures: Dr. Allison Zibelli:  None Disclosed   Dr. Erika Hamilton: Consulting or Advisory Role (Inst): Pfizer, Genentech/Roche, Lilly, Daiichi Sankyo, Mersana, AstraZeneca, Novartis, Ellipses Pharma, Olema Pharmaceuticals, Stemline Therapeutics, Tubulis, Verascity Science, Theratechnologies, Accutar Biotechnology, Entos, Fosun Pharma, Gilead Sciences, Jazz Pharmaceuticals, Medical Pharma Services, Hosun Pharma, Zentalis Pharmaceuticals, Jefferies, Tempus Labs, Arvinas, Circle Pharma, Janssen, Johnson and Johnson   Research Funding (Inst): AstraZeneca, Hutchison MediPharma, OncoMed, MedImmune, Stem CentRx, Genentech/Roche, Curis, Verastem, Zymeworks, Syndax, Lycera, Rgenix, Novartis, Millenium, TapImmune, Inc., Lilly, Pfizer, Lilly, Pfizer, Tesaro, Boehringer Ingelheim, H3 Biomedicine, Radius Health, Acerta Pharma, Macrogenics, Abbvie, Immunomedics, Fujifilm, eFFECTOR Therapeutics, Merus, Nucana, Regeneron, Leap Therapeutics, Taiho Pharmaceuticals, EMD Serono, Daiichi Sankyo, ArQule, Syros Pharmaceuticals, Clovis Oncology, CytomX Therapeutics, InventisBio, Deciphera, Sermonix Pharmaceuticals, Zenith Epigentics, Arvinas, Harpoon, Black Diamond, Orinove, Molecular Templates, Seattle Genetics, Compugen, GI Therapeutics, Karyopharm Therapeutics, Dana-Farber Cancer Hospital, Shattuck Labs, PharmaMar, Olema Pharmaceuticals, Immunogen, Plexxikon, Amgen, Akesobio Australia, ADC Therapeutics, AtlasMedx, Aravive, Ellipses Pharma, Incyte, MabSpace Biosciences, ORIC Pharmaceuticals, Pieris Pharmaceuticals, Pieris Pharmaceuticals, Pionyr, Repetoire Immune Medicines, Treadwell Therapeutics, Accutar Biotech, Artios, Bliss Biopharmaceutical, Cascadian Therapeutics, Dantari, Duality Biologics, Elucida Oncology, Infinity Pharmaceuticals, Relay Therapeutics, Tolmar, Torque, BeiGene, Context Therapeutics, K-Group Beta, Kind Pharmaceuticals, Loxo Oncology, Oncothyreon, Orum Therapeutics, Prelude Therapeutics, Profound Bio, Cullinan Oncology, Bristol-Myers Squib, Eisai, Fochon Pharmaceuticals, Gilead Sciences, Inspirna, Myriad Genetics, Silverback Therapeutics, Stemline Therapeutics

Law contracts done right are a small business owner's best friend. They will protect your personal assets. They will protect potential clients from stealing your work and not hiring you, which happens more often than you think. Sharon L. Tasmin is a seasoned business and technology attorney with over 30 years of experience in law and over 10 years as a businesswoman. Having spent 15 years at HoganLovells, one of the world's largest law firms, and serving as in-house counsel at MedImmune, Sharon founded HTBiz Law to offer clients the best of both worlds—a boutique law firm experience with the expertise of a global firm. Contracts don't have to be scary. Your clients and customers sign things all the time. They sign contracts daily but may not think of them as contracts.  "If somebody refuses to do business with you because you want them to sign a contract that protects you and still gives your client or customer what they need run because that's the potential client that will not pay," says Sharon. They will likely leave bad reviews. They will likely have unreasonable expectations. The contract protects both of you. The single greatest disagreement between service providers, consultants, business owners, and their customers is when there isn't a clear understanding of what you are going to do, for how much money, and in what time, versus what they were going to get in, what time, and for how much. The simplest way to solve that problem is to put it all in writing and sign. Sharon says not all money is good money, and not all clients are good clients for you. "The hardest decision a new business owner will make when they are new and desperate for money is 'I must take every bit of work that comes in the door,' and that is 100% the wrong thing," says Sharon. "If you are so desperate or foresee that you will be so desperate that you will not be able to say no, you're not ready to start your business as your full-time job yet."  "The first thing you need to do is file an LLC and it will be the best one to 300 hundred dollars you will ever spend. If you can't afford that, for sure you should not be starting a business." This creates a distinction in the eyes of the law between you as a business and you as a person. Without it, if you make a mistake and get sued, all your personal assets are at risk -- your house, your car, your savings. Next, do the inventory. Think of everything you've created, and then make sure that you're taking that into account in the rates you charge. Do you add $25 an hour? Is it a flat fee? "If you take the project that absorbs 40 hours a week of your time, it isn't just that it may not be the right client and you may be getting paid less for this project, it's you're losing the opportunity cost of something else," says Sharon. Get "Securing Your Brilliance: A Hands-On Workbook for Copyright & IP Protection" to help you identify and protect your valuable digital and intellectual property assets: https://www.htbizlaw.com/workbook It usually is $19.95, but with the promo code "GAMEON" it will be only $9.95. Connect with Sharon: https://www.htbizlaw.com LinkedIn: https://www.linkedin.com/in/sharontasman/ Other GoG episodes you might want to check out: Business Cash Flow: How to Pay Yourself (and the IRS) Consistently https://sarahwalton.com/business-cashflow/ How to Manage Your Money Before Divorce https://sarahwalton.com/financial-planning-for-divorce/ You can check out our podcast interviews on YouTube, too! http://bit.ly/YouTubeSWalton  Thank you so much for listening. I'm so honored that you're here and would be so grateful if you could leave a quick review on Apple Podcasts by clicking here, scrolling to the bottom, and clicking “Write a review.” Then we'll get to inspire even more people! (If you're not sure how to leave a review, you can watch this quick tutorial.) #AssetProtection #ProtectAssets #LawsuitProtection #Law #WomenEntrepreneursSuccessStories #WomenEntrepreneurs #WomenInBusiness #WomenEmpowerment #BusinessCoach #SalesCoach    

Dr. Neeraj Agarwal and Dr. Jeanny Aragon-Ching discuss promising combination therapies and other compelling advances in genitourinary cancers in advance of the 2024 ASCO Annual Meeting. TRANSCRIPT Dr. Neeraj Agarwal: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, your guest host of the ASCO Daily News Podcast today. I'm the director of the Genitourinary Oncology Program and a professor of medicine at the University of Utah Huntsman Cancer Institute, and editor-in-chief of the ASCO Daily News. I'm delighted to be joined by Dr. Jeanny Aragon-Ching, a GU medical oncologist and the clinical program director of genitourinary cancers at the Inova Schar Cancer Institute in Virginia. Today, we will be discussing some key abstracts in GU oncology that will be featured at the 2024 ASCO Annual Meeting.  Our full disclosures are available in the transcript of this episode. Jeanny, it's great to have you on the podcast. Dr. Jeanny Aragon-Ching: Thank you so much, Dr. Agarwal. It's a pleasure to be here. Dr. Neeraj Agarwal: So, Jeanny, let's start with some bladder cancer abstracts. Could you tell us about the Abstract 4509 titled, “Characterization of Complete Responders to Nivolumab plus Gemcitabine Cisplatin versus Gemcitabine Cisplatin Alone in Patients with Lymph Node Only Metastatic Urothelial Carcinoma from the CheckMate 901 Trial.”  Dr. Jeanny Aragon-Ching: Of course, Neeraj, I would be delighted to. First, I would like to remind our listeners that the CheckMate 901 trial was a randomized, open-label, phase 3 study, in which this particular sub-study looked at cisplatin-eligible patients with previously untreated, unresectable, or metastatic urothelial carcinoma who were assigned to receive the combination of gemcitabine and cisplatin, followed by up to 2 years of nivolumab or placebo. Based on the data presented at ESMO 2023 and subsequently published in the New England Journal of Medicine, which shows significantly improved progression-free survival and overall survival in patients receiving the combination of gemcitabine, cisplatin, and nivolumab, this regimen was approved in March 2024 as a first-line therapy for patients with unresectable or metastatic urothelial carcinoma.  In the abstract that will be featured at ASCO this year, Dr. Matt Galsky and colleagues present a post-hoc analysis that aims to characterize a subset of patients with complete response as well as those with lymph node-only metastatic disease. In patients receiving the experimental treatment, 21.7% achieved a complete response, while 11.8% of the patients in the control arm achieved a complete response.  Among these complete responders, around 52% had lymph- node-only disease in both arms. Furthermore, when characterizing the subgroup of patients with lymph-node-only disease, those receiving the combination of gemcitabine-cisplatin plus nivolumab had a 62% reduction in the risk of progression or death and a 42% reduction in the risk of death compared to those treated with gemcitabine-cisplatin alone.  The median overall survival in the experimental arm in this subgroup was around 46.3 months, while it was only 24.9 months in the control arm. The ORR in patients with lymph-node-only disease receiving gem-cis plus nivo was about 81.5% compared to 64.3% in those treated with gem-cis alone. Dr. Neeraj Agarwal: Thank you, Jeanny, for the excellent summary of this abstract. We can say that nivolumab plus gemcitabine-cisplatin induced durable disease control and clinically meaningful improvements in OS and PFS compared to gem-cis alone in patients with lymph- node-only metastasis, and deserves to be considered as one of the options for these patients.  In a similar first-line metastatic urothelial carcinoma setting, Abstract 4502, also reported data on a recently approved combination of enfortumab vedotin and pembrolizumab. Can you tell us more about this abstract, Jeanny? Dr. Jeanny Aragon-Ching: Sure, Neeraj. So, as quick reminder to our audience, this regimen was tested in the EV-302 phase 3 trial, where patients with previously untreated, locally advanced or metastatic urothelial carcinoma were randomized to receive enfortumab vedotin, plus pembrolizumab or gemcitabine plus either cisplatin or carboplatin. These data were also first presented at ESMO 2023 and subsequently published in the New England Journal of Medicine. They showed that this immune based combination significantly improved both progression free survival and overall survival, which were the primary endpoints compared to chemotherapy. In this abstract, Dr. Shilpa Gupta from the Cleveland Clinic and colleagues present the results of patient reported outcomes based on quality-of-life questionnaires in this trial.  Time to pain progression and time to confirm deterioration were numerically longer in patients treated with EV plus pembro, and patients with moderate to severe pain at baseline receiving this combination had a meaningful improvement in the Brief Pain Inventory Short-Form worst pain from week 3 through 26. Dr. Neeraj Agarwal: Thank you, Jeanny. This means that patients treated with EV plus pembro did not only have improved survival compared with platinum-based chemotherapy, but also improvement in their quality-of-life and functioning, further supporting the value of this combination for patients with locally advanced or metastatic urothelial carcinoma. This is terrific news for all of our patients.   Before we wrap up the bladder cancer section, would you like to tell our listeners about Abstract 4565, which provides the data on the efficacy of trastuzumab deruxtecan in patients with bladder cancer? Dr. Jeanny Aragon-Ching: Yes, Neeraj; this is timely given the recent FDA approval, which we will talk about. The abstract is titled, “Efficacy and Safety of Trastuzumab Deruxtecan in Patients with HER2 Expressing Solid Tumors: Results from the Bladder Cohort of the DESTINY-PanTumor02 Study.” And as a quick reminder, the DESTINY-PanTumor02 was a phase 2 open-label study where trastuzumab deruxtecan, an antibody-drug conjugate targeting HER2 expression on cancer cells, was evaluated in patients with HER2-expressing locally advanced or metastatic disease who previously received systemic treatment or who had no other treatment options. The expression of HER2 was evaluated on immunohistochemistry by local or central testing.   The primary endpoint was confirmed objective response rate by investigator assessment. Secondary endpoints included duration of response, progression free survival, disease control rate, and safety. The primary analysis, which was published in the Journal of Clinical Oncology, showed an ORR of 37.1% and responses across all cohorts and the median duration of response was 11.3 months. Based on these results, fam-trastuzumab deruxtecan-nxki was just granted accelerated FDA approval for unresectable or metastatic HER2-positive solid tumors in April 2024.  So, back to this abstract; Dr. Wysocki and colleagues report the results of the bladder cancer cohort. This study included 41 patients with urothelial cancer and at a median follow up of around 12.6 months, the objective response rate among these patients was 39%, the median PFS was 7 months, and the duration of response median was 8.7 months. The disease control rate at 12 weeks was around 71%. Regarding the safety profile, 41.5% of patients experienced grade ≥3 drug related adverse events and interstitial lung disease or pneumonitis did occur in about 4 patients. Although there was no statistical comparison between different groups, the ORR was numerically highest among the HER2 3+ group with 56.3%.  Dr. Neeraj Agarwal: Thank you, Jeanny. So, these data support consideration of trastuzumab deruxtecan as a salvage therapy option for pre-treated patients with HER2 expressing urothelial cancers and show that we are extending our treatment options to include therapies with novel mechanisms of action. This is definitely exciting news for patients with bladder cancer. Dr. Jeanny Aragon-Ching: Yes, absolutely, Neeraj. Now, let's switch gears a bit to prostate cancer. Could you tell us about Abstract 5005 which is titled, “EMBARK Post Hoc Analysis of Impact of Treatment Suspension on Health Quality-of-Life?” Dr. Neeraj Agarwal: Of course, I'd be happy to. So, enzalutamide was recently granted FDA approval for the treatment of patients with non-metastatic castration-sensitive prostate cancer with biochemical recurrence at high-risk of metastasis, based on the results of the EMBARK trial, which was a phase 3 study where patients with high-risk biochemical recurrence were randomized to receive either enzalutamide with leuprolide, enzalutamide monotherapy, or placebo plus leuprolide. The primary endpoint was metastasis-free survival with secondary endpoints including overall survival and safety.  Results showed that patients receiving enzalutamide alone or enzalutamide plus leuprolide had significantly improved metastasis-free survival compared to those treated with leuprolide alone while preserving health-related quality-of-life.   One important aspect in the design of the trial was that patients who achieved undetectable PSA at week 37 underwent treatment suspension. The treatment was resumed if PSA rose to more than 2 ng/ml for patients who underwent radical proctectomy or when PSA rose to more than 5 ng/ml for those who did not undergo surgery.  In this abstract, Dr. Stephen Freedland and colleagues present a post-hoc analysis of health-related quality-of-life outcomes after treatment suspension between weeks 37 and 205. They found that treatment was suspended in 90.9% of patients receiving enzalutamide plus leuprolide, 85.9% of those receiving enzalutamide monotherapy, and 67.8% of those receiving leuprolide monotherapy. Among those patients who stayed on treatment suspension, a trend toward numerical improvement in health-related quality-of-life after week 37 was seen in all 3 arms and this reached clinically meaningful threshold at week 205 in pain questionnaires, physical well-being, urinary and bowel symptoms. For hormonal treatment side effects, all arms reached clinically meaningful improvement at the subsequent assessments of week 49 to week 97. However, patients slowly deteriorated, with clinically meaningful deterioration at week 205 relative to week 37 in patients receiving the combination of enzalutamide and leuprolide and those treated with leuprolide.    Concerning sexual activity, a clinically meaningful improvement was reported only in patients receiving enzalutamide plus leuprolide, possibly because sexual function was better preserved prior to suspension in the enzalutamide monotherapy arm and thus there was less opportunity for “improvement” while on suspension.  Dr. Jeanny Aragon-Ching: Thank you, Neeraj, for this great summary. This analysis confirms that treatment suspension in good responders might lead to a clinically meaningful improvements in health-related quality-of-life.   Now, moving on to patients with metastatic castration-resistant prostate cancer, what can you tell us, about Abstract 5008 titled, “Baseline ctDNA analyses and associations with outcomes in taxane-naive patients with mCRPC treated with 177Lu-PSMA-617 versus change of ARPI in PSMAfore”?  Dr. Neeraj Agarwal: Sure, Jeanny. The PSMAfore trial was a phase 3 study that compared the efficacy of 177Lu-PSMA-617 versus an ARPI switch in patients with mCRPC and prior progression on a first ARPI, and not previously exposed to docetaxel chemotherapy. The primary endpoint was rPFS and OS was an important secondary endpoint. The primary analysis presented at ESMO 2023 showed a significantly prolonged rPFS in patients receiving lutetium. In the abstract that will be featured at the 2024 ASCO Annual Meeting, Dr. Johann De Bono and colleagues present an exploratory analysis regarding the associations between baseline circulating tumor DNA and outcomes.  ctDNA fraction was evaluated in all samples as well as alterations in key prostate cancer drivers prevalent in more than 10% of participants.  The investigators sought to interrogate the association of ctDNA fraction or alterations with rPFS, PSA response, and RECIST response at data cutoff. They showed that median rPFS was significantly shorter in patients with a ctDNA fraction >1% compared to those with a fraction < 1% regardless of the treatment arm. Furthermore, ctDNA fraction >1% was also associated with worst RECIST response and PSA50 response. Regarding prostate cancer drivers, median rPFS was significantly shorter in patients with alterations in the AR, TP53 or PTEN in both treatment arms. There was no significant association between ctDNA alterations and PSA or objective responses. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. So, these results show that the presence of a ctDNA fraction >1% or alterations in AR, P53 and PTEN were all associated with worse outcomes regardless of treatment with lutetium or change in the ARPI. These data are definitely important for counseling and prognostication of patients in the clinic and may guide the design of future clinical trials. Let's move on to kidney cancer. Neeraj, do you have any updates for us?  Dr. Neeraj Agarwal:  Sure. In Abstract 4512 titled, “A Multi-institution Analysis of Outcomes with First-Line Therapy for 99 Patients with Metastatic Chromophobe Renal Cell Carcinoma,” Dr. Sahil Doshi and colleagues present a retrospective, multi-institutional study comparing survival outcomes, including time-to-treatment failure and overall survival, between different first-line treatment options in patients with metastatic chromophobe renal cell carcinoma, where limited clinical trial data exists to guide systemic therapy. They categorized patients into 4 treatment groups: and immune checkpoint inhibitors + targeted therapy doublets (such as ICI VEGF TKI); pure immune checkpoint inhibitor monotherapy and doublets (such as ipilimumab plus nivolumab); targeted therapy doublets (such as lenvatinib plus everolimus), and targeted monotherapy (such as sunitinib).  They identified 99 patients, of whom 54 patients received targeted monotherapy, 17 received ICI VEGF-TKI, 14 received targeted doublet, and 14 patients received only ICI therapies. So the patients treated with any doublet containing a targeted agent had a 52% decrease in the risk of treatment failure and a 44% decrease in the risk of death compared to those treated with targeted monotherapy. The median time to treatment failure was 15 months with IO-targeted doublet, and the median overall survival was 56 months. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. So, these results show that targeted doublet regimens resulted in a longer time to treatment failure and overall survival compared to any monotherapy in patients with chromophobe metastatic RCC and definitely provides valuable insights on treatment selection, albeit I would say there's still a small number of patients that were included in this retrospective analysis. Dr. Neeraj Agarwal: I completely agree this is a relatively small number of patients, but I decided to highlight the abstract given how rare the cancer is, and it is highly unlikely that we'll see large randomized clinical trials in patients with metastatic chromophobe renal cell carcinoma.  So, before we wrap up the podcast, what would you like to tell us about Abstract 5009 which is titled, “A Phase II Trial of Pembrolizumab Platinum Based Chemotherapy as First Line Systemic Therapy in Advanced Penile Cancer: HERCULES (LACOG 0218) Trial.” Dr. Jeanny Aragon-Ching: I'm glad you brought this up, Neeraj. As our listeners may know, advanced penile squamous cell carcinoma has a poor prognosis with limited treatment options. From this perspective, the results of the LACOG 0218 trial are very important. As you mentioned, this was a phase 2 single-arm study evaluating the addition of pembrolizumab to platinum-based chemotherapy as first-line treatment in patients with metastatic or locally advanced penile squamous cell carcinoma not amenable to curative therapy. Patients enrolled received chemotherapy, namely 5-Fluorouracil with cisplatin or carboplatin and pembrolizumab 200 mg IV every 3 weeks for 6 cycles, followed by pembrolizumab 200 mg IV every 3 weeks up to 34 cycles. The primary endpoint was confirmed overall response rate by investigator assessment.  In the 33 patients eligible for the efficacy analysis, the confirmed ORR by investigator assessment was 39.4% and included one complete response and 12 partial responses. The confirmed ORR was 75% in patients with high TMB and 55.6% in patients positive for HPV16, making TMB and HPV16 potential predictive biomarkers for efficacy in this study. Concerning the toxicity profile, any grade treatment-related adverse events were reported in around 92% of patients, and grade 3 or more treatment-related adverse events occurred in 51% of patients. 10.8% of patients discontinued treatment due to adverse events.  Dr. Neeraj Agarwal: Thank you, Jeanny. I would like to add that HERCULES is the first trial to demonstrate the efficacy of an immune checkpoint inhibitor in advanced penile squamous cell carcinoma with a manageable safety profile. Thus, the combination of ICI with platinum-based chemotherapy is a promising treatment for advanced penile squamous cell carcinoma and warrants further investigation.  Dr. Jeanny Aragon-Ching: I agree, Neeraj. Any final remarks before we conclude today's podcast? Dr. Neeraj Agarwal: Jeanny, I really want to thank you for your participation and valuable insights. Your contributions are always appreciated, and I sincerely thank you for taking the time to join us today. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. It was a pleasure.  Dr. Neeraj Agarwal:  As we bring this podcast to an end, I would like to acknowledge the significant advances happening in the treatment of patients with genitourinary cancers. During our upcoming 2024 ASCO Annual Meeting, there will be an array of different studies featuring practice-changing data presented by researchers and physicians from around the globe. I urge our listeners to not only participate in this event to celebrate these achievements, but to also play a role in sharing these cutting-edge data with healthcare professionals worldwide. Through our collective efforts, we can surely optimize the benefits of patients on a global scale.   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 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. Thank you very much.   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. Neeraj Agarwal  @neerajaiims  Dr. Jeanny Aragon-Ching    Follow ASCO on social media:   @ASCO on Twitter     ASCO on Facebook     ASCO on LinkedIn       Disclosures:    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. Jeanny Aragon-Ching:  Honoraria: Bristol-Myers Squibb, EMD Serono, Astellas Scientific and Medical Affairs Inc., Pfizer/EMD Serono  Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant, Exelixis,   Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb, Astellas/Seattle Genetics. 

Drs. Shaalan Beg and Aparna Parikh discuss the role of ctDNA as a powerful prognostic biomarker for GI cancers, along with its impact on risk stratification and the detection of recurrence. They highlight key studies in ctDNA that were featured at the 2024 ASCO GI Cancers Symposium, including COBRA, GALAXY, and BESPOKE in CRC, as well as the promise of ctDNA testing in the preoperative detection of iCCA. TRANSCRIPT Dr. Shaalan Beg: Hello, and welcome to the ASCO Daily News Podcast. I am Dr. Shaalan Beg, your guest host for the ASCO Daily News Podcast today. I am an adjunct associate professor at UT Southwestern's Harold Simmons Comprehensive Cancer Center in Dallas. On today's episode, we will be discussing the emergence of circulating tumor DNA (ctDNA) technology in GI cancers. I am delighted to be joined by Dr. Aparna Parikh, an assistant professor of medicine at Harvard University and the director for colorectal medical oncology at the Massachusetts General Hospital Cancer Center, where she also serves as the medical director of the Young Adult Colorectal Cancer Center. Dr. Parikh will share her insights on key research on this hot topic in GI oncology that was featured at the recent ASCO Gastrointestinal Cancers Symposium.  Our full disclosures are available in the transcripts of this episode, and disclosures related to all episodes of the podcast are available at asco.org/DNpod.  Dr. Parikh, it's great to have you on the podcast today. Dr. Aparna Parikh: Thanks so much, Dr. Beg.  Dr. Shaalan Beg: In recent years, it has become evident that liquid biopsy and other emerging ctDNA technologies are changing how we treat GI cancers, and colorectal cancer (CRC) is in the forefront of this space. Before we dive into key studies, can you briefly highlight for our listeners how ctDNA is advancing the field and how it can influence the care that we deliver to our patients in the future? Dr. Aparna Parikh: Absolutely, ctDNA is certainly a hot topic. What we have learned over the years is that ctDNA has emerged across many solid tumor types as one of the most powerful, if not the most powerful, prognostic biomarker we have to date. ctDNA has improved risk stratification. We have learned a lot about the role in what is called minimal or molecular residual disease in patients with early-stage disease, and ctDNA being a biomarker of recurrence for those patients, with ctDNA, we have a better understanding of tumoral heterogeneity, both spatially and temporally, getting a better glimpse of what is happening in a given patient with multiple metastases, as well as genomic evolution of tumors over time. So certainly many, many roles and areas where ctDNA is emerging. Dr. Shaalan Beg: This was a hot topic at the 2024 ASCO GI Cancers Symposium, and we're going to take a deep dive into some of the abstracts that were presented. Let's start with the COBRA study, which is the NRG-GI005. That was Abstract 5 at the ASCO GI Cancers Symposium, and the GALAXY study, which was Abstract 6 at the symposium. So, the COBRA study reported results of ctDNA as a predictive biomarker in adjuvant chemotherapy for people with colon cancer. At a high level, it was a negative study, but there are some important lessons for us to learn. Similarly, in the GALAXY study, investigators from Japan presented an updated analysis on the correlation of ctDNA dynamics with outcomes in colorectal cancer with minimal residual disease. How do you synthesize all this information and help the listeners understand our current state for ctDNA applications in colorectal cancer? Dr. Aparna Parikh: Yeah. Let's take the COBRA study first. Let's talk a little bit about the design of COBRA. COBRA was intended to look at patients that were resected, stage 2 colorectal cancer patients, or colon cancer patients who were 2A. These are patients where the treating physician would, at the outset, decide that there was no adjuvant chemotherapy indicated. These are patients where active surveillance would be entirely appropriate as the standard of care. Patients were randomized to arm 1, which was active surveillance, or randomized to arm 2, which was assay-directed therapy. If there were ctDNA positive in arm 2, then they were given chemotherapy, FOLFOX or CAPOX. And if they were “ctDNA not detected,” then they would also go on to active surveillance.   And so, the plan was that nearly 1,500 patients are to be recruited, and at the time of this data cut, they had around 630-some patients. The primary objective was to look at the clearance rates of ctDNA between the ctDNA-positive cohorts, remember, the chemotherapy and the active surveillance cohorts at 6 months. They had around a 5% detection rate of ctDNA patients. Ultimately, that was around 16 patients. The reason that the study shut down was that what they found was that in the surveillance arm, the arm that was not getting any treatment, they had a ctDNA clearance of 43% versus 11% in the chemotherapy arm. They had an interim analysis to look at the clearance rate between the 2 arms, and what was surprising to the investigators and the community was what was happening in terms of clearance. Why do we have a 43% clearance rate in patients that were not getting anything? And so, because of that, the study was shut down as it did not meet its prespecified interim look at clearance in those 2 arms.   Many things came up in terms of learnings from COBRA. Number one was the characteristics of the assay. And so, you take an assay in a low-risk patient population that has a fixed specificity, and when your baseline prevalence of recurrence is so low, for example, in low-risk stage 2 patients, your composite predictive value is very susceptible to small changes in that specificity. And so, your PPV is going to be a lot lower in a low-risk patient population than a higher-risk patient population. The COBRA study used an older version of a tumor-uninformed assay, so it definitely called into question some characteristics of the assay. Is one-time-point clearance sufficient, and is that the right endpoint? We have seen now, including the GALAXY study that we'll talk about here, previously reported just spontaneous clearance happening in 5%, 10% of patients. The question with that spontaneous clearance is: Was it actually clearance, or was chemotherapy just perhaps in a low ctDNA shedding state? Are you just suppressing the ctDNA below the level of limited detection?  And then in this study, the clearance draw was actually done in the chemotherapy arm right before the last cycle of chemotherapy, again to that point of, are you just suppressing the ctDNA with chemotherapy? There is also stochastic sampling error that can happen in patients with very low residual tumor volume. So, I think this is a disappointing study in the sense that it is still a really important question. There are still 2A patients that recur, but maybe [this was] not the right test, or maybe single-time-point testing wasn't enough. And so, lots of lessons to be learned from this study in terms of test and design, but hopefully more to come. I think certainly stage 2 patients remain an area where I think, hopefully, ctDNA still plays a factor for those patients.  Dr. Shaalan Beg: And how was the patient population for the GALAXY study? That was Abstract 6, compared to the COBRA study. Could you summarize those findings for us?  Dr. Aparna Parikh: Yeah, so GALAXY was part of a large study in Japan that includes an observational cohort plus therapeutic cohorts as well. And so, GALAXY was just further reporting of the observational cohort. So unlike COBRA, which is a low-risk, stage 2 study that was actually asking that interventional question: Can you use it to guide therapy? The GALAXY and the updated GALAXY just continues to show more clinical validity data rather than clinical utility data. And it was nearly 3,000 patients, pan stages. Again, the lion's share were stage 2 and 3 patients, but there were also stage 1 and stage 4 patients as well. And what they showed was that ctDNA is undoubtedly prognostic. They showed very consistent Kaplan-Meier curves, which we've seen time and time again, where if you're ctDNA-positive, you don't do as well.  What they showed was, not surprisingly, with longer-term follow-up – this is 24-month follow up, so longer-term follow up than was published in their paper last year – was that when you test at one time point, so landmark testing, the sensitivity of detecting recurrence was around 48%, and that fell from the publication last year which was around 58%, 59%, which is not surprising as you follow more people. I think single time point testing soon after surgery may miss those late recurrences, but it's still prognostic and showed a specificity of around 94%.   They also continued to show that if you continued to test with serial testing, your sensitivity improves, but what was really interesting and new, what they presented this time, was a clearance analysis. And showing, again, comparable to COBRA, in many ways, in the sense that clearance can be a little bit finicky, especially at one time point, is what they showed is that patients who had sustained clearance, and these are patients that had at least two time points with their ctDNA remained to be negative, they did very well. But if you had transient clearance, and again, the definition was a little bit broad, at least having one negative and then one positive, those patients ultimately, at 24 months, the curves came together with the no clearance curve. So initially, they did better than the people that didn't have any clearance. But if you transiently cleared at two years, the curves came back together.   And what was interesting is that in those patients that sort of transiently clear by 9 to 12 months, 80% of those are actually having a rapid return of ctDNA. And so this begs the question of was chemotherapy just suppressing that ctDNA or maybe if you have a better test you could have actually improved it.  These were some of the updated, interesting learnings from GALAXY, which remains incredibly prognostic. And then the concept of clearance, which I think we have to look into a little bit more as a field, and understanding that maybe just one time point clearance isn't sufficient.  Dr. Shaalan Beg: Yeah, and one of the most important applications for ctDNA can be its ability to inform adjuvant chemotherapy. Its ability to not only identify more people who may benefit from chemotherapy, but maybe even identify people who don't need chemotherapy. And along those lines, Abstract 9, the BESPOKE study, looked to understand the role of ctDNA-based detection of molecular residual disease to inform adjuvant therapy for stage 2 and 3 colorectal cancer. And they presented interim data at the GI ASCO this year. What were your takeaways from this study? Dr. Aparna Parikh: Exactly. Beyond the prognostic implications, I think what was really interesting was that there was the initial data looking at the benefit of adjuvant chemotherapy. So, what they did was they said, “Okay. We're going to take the MRD-positive patients and look at the benefit of adjuvant chemotherapy and then the benefit of adjuvant chemotherapy in the MRD-negative patients.” And again, remember, this is a prospective observational study, so it's not looking at negative and positive to guide therapy, but it's just looking prospectively and observationally at how those patients are doing. But what they showed again is that indeed, in the adjuvant chemotherapy group, the benefit of adjuvant chemotherapy again with the follow-up to date on the study was different in the MRD-positive patients.  First of all, I guess taking a step back, the DFS in the ctDNA-negative patients at 2 years was very good. So negative patients had over 98% 2-year DFS in both the adjuvant chemotherapy and observational group. And there was no real difference between adjuvant or not. But in the positive patients, not surprisingly, the DFS was worse. But what was reassuring to see is that you can make an impact with adjuvant chemotherapy in the positive patients. And the difference in DFS between the positive and negative patients, with adjuvant or not, was 42% versus 12.5%, in the observational patients. So, it is benefitting the patients who are positive so it does give us more data that, again, at least in the positive patients, you may be able to reverse the recurrences there with adjuvant chemotherapy. And maybe if you're negative, eventually, we'll get to a point of de-escalation of care. Again, keeping in mind the kinds of sensitivity limitations as well.  Dr. Shaalan Beg: Wonderful. And one of the other malignancies in the GI space where precision therapies and molecular biomarkers are making a huge difference are intrahepatic cholangiocarcinoma. Genomic profiling using ctDNA is increasingly being used in this population to inform precision oncology approaches and determine mechanisms of resistance to targeted therapies as well. In Abstract 528, investigators looked at the role of preoperative ctDNA testing for resectable intrahepatic cholangiocarcinoma. What are your thoughts on that study?  Dr. Aparna Parikh: Yeah, it's such an important area, as you mentioned, in the metastatic space – FGFR, IDH1, all these alterations that are emerging in intrahepatic cholangios. This was a very small study, it was preoperative, and so the tumor was intact, and around 14 patients. They used a tumor-informed approach just for detection and quantification of ctDNA. So this was not a study that was looking at a next-generation sequencing approach where you're going to actually be able to detect the alterations, but it's actually looking for the detection and quantification of ctDNA rather than genomic characterizations. And patients had about a month or so where they had their baseline blood detected. And I think what was reassuring to say was that ctDNA was actually detected in all the patients with the primary tumor intact, except for one patient who was a very low-risk stage 1A patient. There was some correlation, against a small number of patients, between the concentration of ctDNA in patients that had the lower stage and then the higher stage groups. Small numbers were actually hard to characterize and correlate with recurrence or mortality, but at least, some correlation with pathologic tumor size, they were able to because it was a bespoke panel and you're sampling the tissue and then looking in the blood, IDH1 and 2 were mutations that were tracked based on the genomic profiling and a couple of the patients were able to have their IDH mutations tracked.  So it gives us a sense, a little bit, that ctDNA, we know has a lot of variable shedding across disease states and tumor locations, but gives us some promise that it is reliably detected with the tumor-informed approach, at least preoperatively in cholangios. So may again open some more opportunities for MRD testing in cholangiocarcinoma as well.  Dr. Shaalan Beg: Thank you. That's a wonderful review of ctDNA applications in gastrointestinal cancers from the 2024 ASCO GI Cancers Symposium. Thank you, Dr. Parikh, for sharing your valuable insights with us on the podcast today. Dr. Aparna Parikh: Thank you so much for having me. Dr. Shaalan Beg: Thank you to our listeners for your time today. You'll find links to 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.   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. Aparna Parikh @aparna1024   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. Aparna Parikh: Consulting or Advisory Role (An Immediate Family Member): PMV Consulting or Advisory Role: Checkmate Pharmaceuticals, Guardant Health, Foundation Medicine, Abbvie, Value Analytics Labs, Bayer, Taiho Oncology, Delcath, Seagen, CVS, SAGA Diagnostics, Scarce, Illumina, UpToDate, Takeda, AstraZeneca, Takeda, Pfizer, Kahr, Xilio Therapeutics, Sirtex Research Funding: PMV Pharma, Erasca, Inc, Syndax Research Funding (Institution): Bristol-Myers Squibb, Genentech, Guardant Health, Array, Eli Lilly, Novartis Pharmaceuticals UK Ltd., PureTech, Mirati Therapeutics, Daiichi Sankyo, Karkinos Other Relationship: C2i Genomics, Xgenomes, Parithera, Cadex

We're super privileged to chat online with Bahija Jallal, the CEO of Immunocore. Immunocore is the largest biotech in the UK and the 5th largest in Europe with a market cap of just over 3 billion dollars. We talk about how Immunocore has helped thousands of cancer patients and has become a commercial biotech. We also talk about why she thinks gender and race diversity are a business case and how AI is changing protein and biologics engineering.

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

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/SKH865. CME/MOC/AAPA/IPCE credit will be available until March 20, 2025.Making Precision Decisions in the Treatment of NSCLC With Common and Uncommon EGFR Mutations: How to Navigate the Expanding Options and Increasing Complexity In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerJoshua Sabari, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Genentech, Inc.; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Mirati Therapeutics, Inc.; Navire; Pfizer; Regeneron Pharmaceuticals Inc.; Sanofi Genzyme; and Takeda Pharmaceutical Company Limited.Grant/Research Support from Boehringer Ingelheim Pharmaceuticals, Inc.; Janssen Pharmaceuticals, Inc.; Mirati Therapeutics, Inc.; and Regeneron Pharmaceuticals Inc.Faculty/PlannerJyoti D. Patel, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AnHeart Therapeutics; AstraZeneca; Blueprint Medicines Corporation; Daiichi Sankyo, Inc.; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Sanofi; and Takeda Pharmaceutical Company Limited.Other Financial or Material Support for Travel from Daiichi Sankyo, Inc. and Tempus.Faculty/PlannerAlexander I. Spira, MD, PhD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; Array BioPharma Inc.; AstraZeneca/ MedImmune; Black Diamond Therapeutics; Blueprint Medicines Corporation; Bristol Myers Squibb; Daiichi Sankyo, Inc./AstraZeneca; Incyte; Gritstone bio, Inc.; Janssen Research & Development; Jazz Pharmaceuticals, Inc.; Lily; Merck & Co., Inc.; Mersana Therapeutics; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals Inc.; Sanofi; and Takeda Pharmaceutical Company Limited.Grant/Research Support from ADC Therapeutics SA; AbbVie Inc.; Alkermes; Amgen Inc.; Arch Therapeutics, Inc.; ArriVent Biopharma; Astellas Pharma US, Inc.; Astex Pharmaceuticals; AstraZeneca; Black Diamond Therapeutics; Blueprint Medicines Corporation; Bluprint Oncology; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd; Gritstone bio, Inc.; Ignyta Inc; Incyte; Janssen Oncology; LAM Therapeutics, Inc.; Loxo Oncology; MacroGenics, Inc.; Medikine, Inc; MedImmune; Mersana Therapeutics; Mirati Therapeutics, Inc.; NALO Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Plexxikon; Regeneron Pharmaceuticals Inc.; Revolution Medicines, Inc.; Rubius Therapeutics; Scorpion Therapeutics; Synthekine; and Takeda Pharmaceutical Company Limited.Honoraria from Amgen Inc.; AstraZeneca/ MedImmune; Bayer; Bristol Myers Sqiubb; CytomX Therapeutics, Inc.; Janssen Pharmaceuticals, Inc.; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; and Takeda Pharmaceutical Company Limited.Stock Shareholder in Lilly.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/SKH865. CME/MOC/AAPA/IPCE credit will be available until March 20, 2025.Making Precision Decisions in the Treatment of NSCLC With Common and Uncommon EGFR Mutations: How to Navigate the Expanding Options and Increasing Complexity In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerJoshua Sabari, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Genentech, Inc.; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Mirati Therapeutics, Inc.; Navire; Pfizer; Regeneron Pharmaceuticals Inc.; Sanofi Genzyme; and Takeda Pharmaceutical Company Limited.Grant/Research Support from Boehringer Ingelheim Pharmaceuticals, Inc.; Janssen Pharmaceuticals, Inc.; Mirati Therapeutics, Inc.; and Regeneron Pharmaceuticals Inc.Faculty/PlannerJyoti D. Patel, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AnHeart Therapeutics; AstraZeneca; Blueprint Medicines Corporation; Daiichi Sankyo, Inc.; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Sanofi; and Takeda Pharmaceutical Company Limited.Other Financial or Material Support for Travel from Daiichi Sankyo, Inc. and Tempus.Faculty/PlannerAlexander I. Spira, MD, PhD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; Array BioPharma Inc.; AstraZeneca/ MedImmune; Black Diamond Therapeutics; Blueprint Medicines Corporation; Bristol Myers Squibb; Daiichi Sankyo, Inc./AstraZeneca; Incyte; Gritstone bio, Inc.; Janssen Research & Development; Jazz Pharmaceuticals, Inc.; Lily; Merck & Co., Inc.; Mersana Therapeutics; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals Inc.; Sanofi; and Takeda Pharmaceutical Company Limited.Grant/Research Support from ADC Therapeutics SA; AbbVie Inc.; Alkermes; Amgen Inc.; Arch Therapeutics, Inc.; ArriVent Biopharma; Astellas Pharma US, Inc.; Astex Pharmaceuticals; AstraZeneca; Black Diamond Therapeutics; Blueprint Medicines Corporation; Bluprint Oncology; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd; Gritstone bio, Inc.; Ignyta Inc; Incyte; Janssen Oncology; LAM Therapeutics, Inc.; Loxo Oncology; MacroGenics, Inc.; Medikine, Inc; MedImmune; Mersana Therapeutics; Mirati Therapeutics, Inc.; NALO Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Plexxikon; Regeneron Pharmaceuticals Inc.; Revolution Medicines, Inc.; Rubius Therapeutics; Scorpion Therapeutics; Synthekine; and Takeda Pharmaceutical Company Limited.Honoraria from Amgen Inc.; AstraZeneca/ MedImmune; Bayer; Bristol Myers Sqiubb; CytomX Therapeutics, Inc.; Janssen Pharmaceuticals, Inc.; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; and Takeda Pharmaceutical Company Limited.Stock Shareholder in Lilly.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/SKH865. CME/MOC/AAPA/IPCE credit will be available until March 20, 2025.Making Precision Decisions in the Treatment of NSCLC With Common and Uncommon EGFR Mutations: How to Navigate the Expanding Options and Increasing Complexity In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerJoshua Sabari, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Genentech, Inc.; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Mirati Therapeutics, Inc.; Navire; Pfizer; Regeneron Pharmaceuticals Inc.; Sanofi Genzyme; and Takeda Pharmaceutical Company Limited.Grant/Research Support from Boehringer Ingelheim Pharmaceuticals, Inc.; Janssen Pharmaceuticals, Inc.; Mirati Therapeutics, Inc.; and Regeneron Pharmaceuticals Inc.Faculty/PlannerJyoti D. Patel, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AnHeart Therapeutics; AstraZeneca; Blueprint Medicines Corporation; Daiichi Sankyo, Inc.; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Sanofi; and Takeda Pharmaceutical Company Limited.Other Financial or Material Support for Travel from Daiichi Sankyo, Inc. and Tempus.Faculty/PlannerAlexander I. Spira, MD, PhD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; Array BioPharma Inc.; AstraZeneca/ MedImmune; Black Diamond Therapeutics; Blueprint Medicines Corporation; Bristol Myers Squibb; Daiichi Sankyo, Inc./AstraZeneca; Incyte; Gritstone bio, Inc.; Janssen Research & Development; Jazz Pharmaceuticals, Inc.; Lily; Merck & Co., Inc.; Mersana Therapeutics; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals Inc.; Sanofi; and Takeda Pharmaceutical Company Limited.Grant/Research Support from ADC Therapeutics SA; AbbVie Inc.; Alkermes; Amgen Inc.; Arch Therapeutics, Inc.; ArriVent Biopharma; Astellas Pharma US, Inc.; Astex Pharmaceuticals; AstraZeneca; Black Diamond Therapeutics; Blueprint Medicines Corporation; Bluprint Oncology; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd; Gritstone bio, Inc.; Ignyta Inc; Incyte; Janssen Oncology; LAM Therapeutics, Inc.; Loxo Oncology; MacroGenics, Inc.; Medikine, Inc; MedImmune; Mersana Therapeutics; Mirati Therapeutics, Inc.; NALO Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Plexxikon; Regeneron Pharmaceuticals Inc.; Revolution Medicines, Inc.; Rubius Therapeutics; Scorpion Therapeutics; Synthekine; and Takeda Pharmaceutical Company Limited.Honoraria from Amgen Inc.; AstraZeneca/ MedImmune; Bayer; Bristol Myers Sqiubb; CytomX Therapeutics, Inc.; Janssen Pharmaceuticals, Inc.; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; and Takeda Pharmaceutical Company Limited.Stock Shareholder in Lilly.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/SKH865. CME/MOC/AAPA/IPCE credit will be available until March 20, 2025.Making Precision Decisions in the Treatment of NSCLC With Common and Uncommon EGFR Mutations: How to Navigate the Expanding Options and Increasing Complexity In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerJoshua Sabari, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Genentech, Inc.; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Mirati Therapeutics, Inc.; Navire; Pfizer; Regeneron Pharmaceuticals Inc.; Sanofi Genzyme; and Takeda Pharmaceutical Company Limited.Grant/Research Support from Boehringer Ingelheim Pharmaceuticals, Inc.; Janssen Pharmaceuticals, Inc.; Mirati Therapeutics, Inc.; and Regeneron Pharmaceuticals Inc.Faculty/PlannerJyoti D. Patel, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AnHeart Therapeutics; AstraZeneca; Blueprint Medicines Corporation; Daiichi Sankyo, Inc.; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Sanofi; and Takeda Pharmaceutical Company Limited.Other Financial or Material Support for Travel from Daiichi Sankyo, Inc. and Tempus.Faculty/PlannerAlexander I. Spira, MD, PhD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; Array BioPharma Inc.; AstraZeneca/ MedImmune; Black Diamond Therapeutics; Blueprint Medicines Corporation; Bristol Myers Squibb; Daiichi Sankyo, Inc./AstraZeneca; Incyte; Gritstone bio, Inc.; Janssen Research & Development; Jazz Pharmaceuticals, Inc.; Lily; Merck & Co., Inc.; Mersana Therapeutics; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals Inc.; Sanofi; and Takeda Pharmaceutical Company Limited.Grant/Research Support from ADC Therapeutics SA; AbbVie Inc.; Alkermes; Amgen Inc.; Arch Therapeutics, Inc.; ArriVent Biopharma; Astellas Pharma US, Inc.; Astex Pharmaceuticals; AstraZeneca; Black Diamond Therapeutics; Blueprint Medicines Corporation; Bluprint Oncology; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd; Gritstone bio, Inc.; Ignyta Inc; Incyte; Janssen Oncology; LAM Therapeutics, Inc.; Loxo Oncology; MacroGenics, Inc.; Medikine, Inc; MedImmune; Mersana Therapeutics; Mirati Therapeutics, Inc.; NALO Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Plexxikon; Regeneron Pharmaceuticals Inc.; Revolution Medicines, Inc.; Rubius Therapeutics; Scorpion Therapeutics; Synthekine; and Takeda Pharmaceutical Company Limited.Honoraria from Amgen Inc.; AstraZeneca/ MedImmune; Bayer; Bristol Myers Sqiubb; CytomX Therapeutics, Inc.; Janssen Pharmaceuticals, Inc.; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; and Takeda Pharmaceutical Company Limited.Stock Shareholder in Lilly.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/SKH865. CME/MOC/AAPA/IPCE credit will be available until March 20, 2025.Making Precision Decisions in the Treatment of NSCLC With Common and Uncommon EGFR Mutations: How to Navigate the Expanding Options and Increasing Complexity In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerJoshua Sabari, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Genentech, Inc.; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Mirati Therapeutics, Inc.; Navire; Pfizer; Regeneron Pharmaceuticals Inc.; Sanofi Genzyme; and Takeda Pharmaceutical Company Limited.Grant/Research Support from Boehringer Ingelheim Pharmaceuticals, Inc.; Janssen Pharmaceuticals, Inc.; Mirati Therapeutics, Inc.; and Regeneron Pharmaceuticals Inc.Faculty/PlannerJyoti D. Patel, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AnHeart Therapeutics; AstraZeneca; Blueprint Medicines Corporation; Daiichi Sankyo, Inc.; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Sanofi; and Takeda Pharmaceutical Company Limited.Other Financial or Material Support for Travel from Daiichi Sankyo, Inc. and Tempus.Faculty/PlannerAlexander I. Spira, MD, PhD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; Array BioPharma Inc.; AstraZeneca/ MedImmune; Black Diamond Therapeutics; Blueprint Medicines Corporation; Bristol Myers Squibb; Daiichi Sankyo, Inc./AstraZeneca; Incyte; Gritstone bio, Inc.; Janssen Research & Development; Jazz Pharmaceuticals, Inc.; Lily; Merck & Co., Inc.; Mersana Therapeutics; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals Inc.; Sanofi; and Takeda Pharmaceutical Company Limited.Grant/Research Support from ADC Therapeutics SA; AbbVie Inc.; Alkermes; Amgen Inc.; Arch Therapeutics, Inc.; ArriVent Biopharma; Astellas Pharma US, Inc.; Astex Pharmaceuticals; AstraZeneca; Black Diamond Therapeutics; Blueprint Medicines Corporation; Bluprint Oncology; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd; Gritstone bio, Inc.; Ignyta Inc; Incyte; Janssen Oncology; LAM Therapeutics, Inc.; Loxo Oncology; MacroGenics, Inc.; Medikine, Inc; MedImmune; Mersana Therapeutics; Mirati Therapeutics, Inc.; NALO Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Plexxikon; Regeneron Pharmaceuticals Inc.; Revolution Medicines, Inc.; Rubius Therapeutics; Scorpion Therapeutics; Synthekine; and Takeda Pharmaceutical Company Limited.Honoraria from Amgen Inc.; AstraZeneca/ MedImmune; Bayer; Bristol Myers Sqiubb; CytomX Therapeutics, Inc.; Janssen Pharmaceuticals, Inc.; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; and Takeda Pharmaceutical Company Limited.Stock Shareholder in Lilly.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/SKH865. CME/MOC/AAPA/IPCE credit will be available until March 20, 2025.Making Precision Decisions in the Treatment of NSCLC With Common and Uncommon EGFR Mutations: How to Navigate the Expanding Options and Increasing Complexity In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerJoshua Sabari, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Genentech, Inc.; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Mirati Therapeutics, Inc.; Navire; Pfizer; Regeneron Pharmaceuticals Inc.; Sanofi Genzyme; and Takeda Pharmaceutical Company Limited.Grant/Research Support from Boehringer Ingelheim Pharmaceuticals, Inc.; Janssen Pharmaceuticals, Inc.; Mirati Therapeutics, Inc.; and Regeneron Pharmaceuticals Inc.Faculty/PlannerJyoti D. Patel, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AnHeart Therapeutics; AstraZeneca; Blueprint Medicines Corporation; Daiichi Sankyo, Inc.; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Sanofi; and Takeda Pharmaceutical Company Limited.Other Financial or Material Support for Travel from Daiichi Sankyo, Inc. and Tempus.Faculty/PlannerAlexander I. Spira, MD, PhD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; Array BioPharma Inc.; AstraZeneca/ MedImmune; Black Diamond Therapeutics; Blueprint Medicines Corporation; Bristol Myers Squibb; Daiichi Sankyo, Inc./AstraZeneca; Incyte; Gritstone bio, Inc.; Janssen Research & Development; Jazz Pharmaceuticals, Inc.; Lily; Merck & Co., Inc.; Mersana Therapeutics; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals Inc.; Sanofi; and Takeda Pharmaceutical Company Limited.Grant/Research Support from ADC Therapeutics SA; AbbVie Inc.; Alkermes; Amgen Inc.; Arch Therapeutics, Inc.; ArriVent Biopharma; Astellas Pharma US, Inc.; Astex Pharmaceuticals; AstraZeneca; Black Diamond Therapeutics; Blueprint Medicines Corporation; Bluprint Oncology; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd; Gritstone bio, Inc.; Ignyta Inc; Incyte; Janssen Oncology; LAM Therapeutics, Inc.; Loxo Oncology; MacroGenics, Inc.; Medikine, Inc; MedImmune; Mersana Therapeutics; Mirati Therapeutics, Inc.; NALO Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Plexxikon; Regeneron Pharmaceuticals Inc.; Revolution Medicines, Inc.; Rubius Therapeutics; Scorpion Therapeutics; Synthekine; and Takeda Pharmaceutical Company Limited.Honoraria from Amgen Inc.; AstraZeneca/ MedImmune; Bayer; Bristol Myers Sqiubb; CytomX Therapeutics, Inc.; Janssen Pharmaceuticals, Inc.; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; and Takeda Pharmaceutical Company Limited.Stock Shareholder in Lilly.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/SKH865. CME/MOC/AAPA/IPCE credit will be available until March 20, 2025.Making Precision Decisions in the Treatment of NSCLC With Common and Uncommon EGFR Mutations: How to Navigate the Expanding Options and Increasing Complexity In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerJoshua Sabari, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Genentech, Inc.; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Mirati Therapeutics, Inc.; Navire; Pfizer; Regeneron Pharmaceuticals Inc.; Sanofi Genzyme; and Takeda Pharmaceutical Company Limited.Grant/Research Support from Boehringer Ingelheim Pharmaceuticals, Inc.; Janssen Pharmaceuticals, Inc.; Mirati Therapeutics, Inc.; and Regeneron Pharmaceuticals Inc.Faculty/PlannerJyoti D. Patel, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AnHeart Therapeutics; AstraZeneca; Blueprint Medicines Corporation; Daiichi Sankyo, Inc.; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Sanofi; and Takeda Pharmaceutical Company Limited.Other Financial or Material Support for Travel from Daiichi Sankyo, Inc. and Tempus.Faculty/PlannerAlexander I. Spira, MD, PhD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; Array BioPharma Inc.; AstraZeneca/ MedImmune; Black Diamond Therapeutics; Blueprint Medicines Corporation; Bristol Myers Squibb; Daiichi Sankyo, Inc./AstraZeneca; Incyte; Gritstone bio, Inc.; Janssen Research & Development; Jazz Pharmaceuticals, Inc.; Lily; Merck & Co., Inc.; Mersana Therapeutics; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals Inc.; Sanofi; and Takeda Pharmaceutical Company Limited.Grant/Research Support from ADC Therapeutics SA; AbbVie Inc.; Alkermes; Amgen Inc.; Arch Therapeutics, Inc.; ArriVent Biopharma; Astellas Pharma US, Inc.; Astex Pharmaceuticals; AstraZeneca; Black Diamond Therapeutics; Blueprint Medicines Corporation; Bluprint Oncology; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd; Gritstone bio, Inc.; Ignyta Inc; Incyte; Janssen Oncology; LAM Therapeutics, Inc.; Loxo Oncology; MacroGenics, Inc.; Medikine, Inc; MedImmune; Mersana Therapeutics; Mirati Therapeutics, Inc.; NALO Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Plexxikon; Regeneron Pharmaceuticals Inc.; Revolution Medicines, Inc.; Rubius Therapeutics; Scorpion Therapeutics; Synthekine; and Takeda Pharmaceutical Company Limited.Honoraria from Amgen Inc.; AstraZeneca/ MedImmune; Bayer; Bristol Myers Sqiubb; CytomX Therapeutics, Inc.; Janssen Pharmaceuticals, Inc.; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; and Takeda Pharmaceutical Company Limited.Stock Shareholder in Lilly.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/SKH865. CME/MOC/AAPA/IPCE credit will be available until March 20, 2025.Making Precision Decisions in the Treatment of NSCLC With Common and Uncommon EGFR Mutations: How to Navigate the Expanding Options and Increasing Complexity In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerJoshua Sabari, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Genentech, Inc.; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Mirati Therapeutics, Inc.; Navire; Pfizer; Regeneron Pharmaceuticals Inc.; Sanofi Genzyme; and Takeda Pharmaceutical Company Limited.Grant/Research Support from Boehringer Ingelheim Pharmaceuticals, Inc.; Janssen Pharmaceuticals, Inc.; Mirati Therapeutics, Inc.; and Regeneron Pharmaceuticals Inc.Faculty/PlannerJyoti D. Patel, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AnHeart Therapeutics; AstraZeneca; Blueprint Medicines Corporation; Daiichi Sankyo, Inc.; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Sanofi; and Takeda Pharmaceutical Company Limited.Other Financial or Material Support for Travel from Daiichi Sankyo, Inc. and Tempus.Faculty/PlannerAlexander I. Spira, MD, PhD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; Array BioPharma Inc.; AstraZeneca/ MedImmune; Black Diamond Therapeutics; Blueprint Medicines Corporation; Bristol Myers Squibb; Daiichi Sankyo, Inc./AstraZeneca; Incyte; Gritstone bio, Inc.; Janssen Research & Development; Jazz Pharmaceuticals, Inc.; Lily; Merck & Co., Inc.; Mersana Therapeutics; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals Inc.; Sanofi; and Takeda Pharmaceutical Company Limited.Grant/Research Support from ADC Therapeutics SA; AbbVie Inc.; Alkermes; Amgen Inc.; Arch Therapeutics, Inc.; ArriVent Biopharma; Astellas Pharma US, Inc.; Astex Pharmaceuticals; AstraZeneca; Black Diamond Therapeutics; Blueprint Medicines Corporation; Bluprint Oncology; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd; Gritstone bio, Inc.; Ignyta Inc; Incyte; Janssen Oncology; LAM Therapeutics, Inc.; Loxo Oncology; MacroGenics, Inc.; Medikine, Inc; MedImmune; Mersana Therapeutics; Mirati Therapeutics, Inc.; NALO Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Plexxikon; Regeneron Pharmaceuticals Inc.; Revolution Medicines, Inc.; Rubius Therapeutics; Scorpion Therapeutics; Synthekine; and Takeda Pharmaceutical Company Limited.Honoraria from Amgen Inc.; AstraZeneca/ MedImmune; Bayer; Bristol Myers Sqiubb; CytomX Therapeutics, Inc.; Janssen Pharmaceuticals, Inc.; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; and Takeda Pharmaceutical Company Limited.Stock Shareholder in Lilly.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

Drs. John Sweetenham and Shaji Kumar discuss the emergence of CAR T-cell therapy for multiple myeloma, its benefits and challenges for patients, and its potential role earlier in the treatment of disease. TRANSCRIPT Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham from the UT Southwestern Harold C. Simmons Comprehensive Cancer Center and host of the ASCO Daily News Podcast.  Multiple myeloma is the second most common hematologic malignancy, and the American Cancer Society estimates that there will be more than 35,000 new cases of the disease diagnosed in the United States this year. The emergence of several novel therapies over the last decade has transformed the therapeutic landscape for multiple myeloma, and chimeric antigen receptor – or CAR T-cell therapy – is one of the newest treatments for this disease, which has created a great deal of buzz.  Dr. Shaji Kumar is an internationally renowned investigator of novel therapeutics and next-generation treatment options for patients with multiple myeloma, and I'm delighted to welcome him to the podcast today to discuss innovations in CAR T-cell therapy in this space. Dr. Kumar is a professor of medicine and chair of the Myeloma Group, as well as chair of research in the Division of Hematology at the Mayo Clinic in Rochester, Minnesota. He is also the editor-in-chief of The Hematologist.  You'll find our full disclosures available in the transcript of this episode, and disclosures of all guests on the podcast are available at asco.org/DNpod.  Shaji, it's great to have you on the podcast today. Dr. Shaji Kumar: Thanks, John. Dr. John Sweetenham: Shaji, to begin with, maybe we could ask you for an overview of where CAR T-cell therapy sits in multiple myeloma right now. We know that CAR T-cell therapy has improved the survival for some patients with myeloma in recent years. But of course, relapse still remains a problem. Can you tell us a little about the therapies that are currently approved for multiple myeloma in the CAR T-cell space, and what are the potential benefits and challenges of these products? Dr. Shaji Kumar: Absolutely. It has been a revolution, I think, in terms of therapies for multiple myeloma during the past decade. We have seen so many new treatments approved for myeloma, and consequently, the survival of patients with myeloma has significantly improved. Two decades ago, we used to tell patients a median survival of 3 years, and today we tell patients a median survival of 8 to 10 years, a number that is continuing to go up. And it is all because of the new treatments that have become available for patients, especially over the past decade, and CAR T-cell therapy has been a game changer.   Now, the main treatments that we were relying on for the past 2 decades have been the immunomodulatory drugs, the proteasome inhibitors, and more recently, the anti-CD38 monoclonal antibodies. Unfortunately, what we see in the clinic is that patients go through these therapies and various combinations of these agents, and often over the 6 to 10 years after the diagnosis, they often become refractory to these drugs. And then we are left with very few choices, if any, for controlling the disease. And that's where the CAR T cells have really made an impact.  Over the past several years, clinical trials have shown that CAR T-cell therapy is highly effective. In fact, when we look at the initial trials that have been done in this space, the majority of these CAR T cells have been targeted towards what we call BCMA, or a B-cell maturation antigen that is present on both normal and abnormal plasma cells. Now, the concept of CAR T cells has been around for a while, and we have already seen success in other hematological malignancies, but it has been a little late compared to the other diseases in terms of its arrival in the myeloma field. But over the past few years, we have seen some dramatic progress. We currently have two different CAR T cells that are approved and available in the clinic. We have idecabtagene vicleucel (ide-cel) and also ciltacabtagene which is also called cilta-cel. Both of these CAR T cells are targeted towards BCMA.   In the early trials conducted with both of these CAR T cells, we've seen patients who have become refractory to all the available therapies, and now upwards of 90% of these patients are responding to these CAR T cells. We are now seeing responses that we had typically not seen previously in any of the other therapies – not only the high response rates but also the depth of response. What we are seeing is a significant number of these patients – nearly half – of these patients can actually be minimal residual disease (MRD)-negative in the bone marrow after the CAR T-cell therapy. And this is clearly unprecedented in this myeloma space. Now, the approval for both these CAR T cells has been based on the experience in patients who have become refractory to the currently available therapies. And the ‘line in the sand' that the FDA has drawn for approval for these drugs has been at least 4 prior therapies. In those patients, when you look at the studies that have been done both for the ide-cel and the cilta-cel, it clearly demonstrates the advantages. And we can look at the data that's available in 3 groups. So we have the single-arm studies, the early phase I and phase 2 trials that have been done with both these CAR T cells. For ide-cel, we have the KarMMa trial, and for the cilta-cel, we have the CARTITUDE trials. In the initial studies, as I previously mentioned, we are seeing responses upwards of 90%, and we are seeing disease control that is lasting at least a year or more with these CAR T cells.   Now, of course, the question is, we do need randomized phase 3 trials to demonstrate that this is indeed true. Even before the phase 3 trials came along, there have been multiple case-control studies that have been done where the outcomes of patients getting these CAR T cells were compared to real-world controls or cohorts of patients who did not get these therapies. And these studies demonstrated that the outcomes of patients getting CAR T cells were significantly better than what has been shown in the real-world controlled population. And then finally, we have, of course, the phase 3 trials that have read out in patients with relapsed myeloma, in fact, in a group of patients in an earlier stage of the disease than who were studied in those single-arm studies. Now, based on the results from the single-arm studies, we got the approval from the FDA for the use of CAR T cells in this late stage of the disease. And with the phase 3 trials that have read out, both the KarMMa-3 trial and the CARTITUDE-4 trial again clearly demonstrate that these CAR T cells are much more effective than what we would have seen with the conventional therapies if those patients were assigned to those treatments. Now, clearly, it's not only a question of efficacy. We also know that they do come with some toxicities, and we have a good sense of the toxicities from those initial phase I and phase 2 trials. Now, as we have seen with the other diseases, the 2 major categories of toxicities that we see are the cytokine release syndrome and the neurological toxicity associated with CAR T-cell therapy.  In terms of the clinical features and the presentations, they are not different than what we have seen with the CAR T cells used in other hematological malignancies, but we do see different frequencies of these in the myeloma patient population. The cytokine release syndrome is something that is seen in a majority of the patients, at least in the lower grades. And over the time since we have been using CAR T-cell therapy, I think we have all become a lot more familiar with the management of the cytokine release syndrome, and we have very effective therapies to manage, and to some extent, maybe even prevent the onset of the cytokine release syndrome in patients undergoing CAR T-cell therapy.  The neurological toxicity is another toxicity that is unique to these immunological therapies, known as the ICANS, or the immune cell effector-associated neurological syndromes. And these, again, thankfully, are much less frequent than what we see with the cytokine release syndrome. But even with the ICANS and other neurological toxicities associated with CAR T-cell therapy, we have a better understanding of the biology behind it, and we also have better modalities to monitor the patients for these toxicities and intervene in an appropriate and timely manner to take care of them.  In addition to the ICANS and the cytokine release syndrome, we certainly do see other toxicities as well. We do see hematological toxicities, which are common for many of the treatments we use for hematological malignancies. Thankfully, these other toxicities can be easily managed. They often reverse themselves over time and haven't really posed any major hurdles in terms of the utilization of these modalities of therapy for patients with myeloma. Dr. John Sweetenham: Okay, that's great. Thank you very much, Shaji. I'll return to some of the potential late effects of CAR T-cell therapy in a moment. But before we get to that, as you know, in other hematologic malignancies, there has been a trend in recent years to moving CAR T-cell therapy further up the therapeutic algorithm, as it were. So there is consideration being given to using this as a first-line or second-line therapy. Do you think there is a potential role for CAR T cell earlier in the treatment of multiple myeloma? For example, could you see a time when it may be used as second-line treatment for this disease? Dr. Shaji Kumar: Absolutely. I think that's a very good point. And I think, just as with other cancers and as with myeloma, too, with many of the therapies we use for myeloma in the newly diagnosed setting or the time of first relapse, were all initially tested in these later relapses. We are following the same script even for the CAR T cells. In fact, the 2 phase 3 trials, the KarMMa-3 trial and the CARTITUDE-4 trial, enrolled patients in the earlier lines of therapy, either 1 prior line or 2 prior lines for these trials. And what we have seen with both phase 3 trials is that the outcomes, both the progression-free survival outcomes and the response rates, are significantly better compared to the standard-of-care therapies that these patients would have otherwise received.  Now, what is unclear at this point is, does every patient at the time of the first relapse need a CAR T-cell therapy, or can we be more selective in terms of deciding which particular subgroup of patients can benefit more from this CAR T-cell therapy in different lines or different relapses? The bottom line is, I think the data that we have right now clearly points towards the utility of CAR T-cell therapy at earlier lines of treatment. The question now is, which patients do we need to do at which stage? In fact, when you look at the newly diagnosed setting, there are ongoing clinical trials that are looking at replacing autologous stem cell transplant with CAR T-cell therapy. Those phase 3 trials are currently enrolling where patients are being randomized to either the autologous stem cell transplant, which is considered a standard of care for eligible patients, or giving them a CAR T-cell therapy. Similarly, even in transplant-ineligible patients, trials are exploring the possibility of using CAR T-cell therapy instead of giving patients a prolonged course of maintenance and consolidation.  One of the beauties with the CAR T-cell therapy right now is that it's a one-time treatment. You get the treatment and you do not get any additional therapies after that. It's a protocol that is being debated – whether we will need maintenance therapies after CAR T-cell therapy, but I think that is something that will have to be explored in the context of clinical trials. But certainly, I think over the next 5 years, we will see the CAR T-cell therapy moving to earlier and earlier lines of therapy. My guess is in 5 years, there will be a subset of patients where we would offer them CAR T-cell as part of the first-line therapy, some others, maybe based on disease and patient characteristics, we might use it at the time of first or second relapse.   Dr. John Sweetenham: Great, thank you. Just to return to toxicities and some of the potential late effects. As you know, last November, the FDA launched an investigation to determine whether CAR T-cell therapy can, in rare cases, cause secondary cancers. You may remember that this was in response to reports of T-cell malignancies in patients who had received various types of CAR T-cell immunotherapies. The FDA determined that the risk of T-cell malignancies is applicable to all of the currently approved BCMA-directed and CD19-directed genetically modified autologous CAR T-cell immunotherapies. Could you care to comment on this whether you have seen any evidence of this in your own work, and whether the events and the FDA investigation have impacted your clinical research or your clinical practice in any way in terms of patient monitoring or maybe in terms of trial approval? Dr. Shaji Kumar: This has been an important observation. As with all new therapies, whenever the question of long-term toxicities is brought up, especially second malignancies, it is something that needs to be looked into very carefully, and I think the FDA is doing exactly that. There have been reports of second cancers, particularly T-cell cancers. In fact, there were some statements that came out recently from the FDA where they commented on the fact that they had seen 22 cases of T-cell cancers by the end of 2023. And, in fact, in 3 of those cases where genetic sequencing was performed, they did notice that the genetic material or the chimeric antigen receptor was inserted into these cancer cells as part of the process. So I think there is a lot more work that needs to be done in terms of understanding the mechanism and probably also understanding how prevalent these instances are.  But I think, based on what we know as of now, these cases form a very tiny fraction of the total number of CAR T-cell therapies that have been used in patients with lymphoma and myeloma. In our own day-to-day practice, this has not really affected how we view this therapy. It clearly has made a significant impact for patients with no other treatment options. So in our daily practice, we continue to use CAR T-cell therapy as we have done before these reports came out. But we do inform patients about the risk and what we know about the risk of these T-cell malignancies.   In addition to T-cell malignancies, there have also been reports of myelodysplastic syndromes in patients undergoing CAR T-cell therapy. Again, it is important to remember that, at least in the myeloma setting, many of these patients have had multiple lines of therapy, often with drugs that can cause second malignancies, particularly myelodysplastic syndrome. So I think a lot more work needs to be done in terms of understanding what is the direct impact of CAR T-cell therapy versus what was lurking underneath because of the treatments that these patients had previously received. So I think it is important for us to continue to be very diligent, as with any new therapies that we introduce for the treatment of our patients. But at the same time, understand that, in the context of the benefits that these therapies bring to our patients, especially when they have no other treatment options.  Dr. John Sweetenham: Absolutely. So, at least for now, and probably in the longer term, the benefits of the therapy certainly appear to outweigh the risks, although it is important not to underestimate or minimize those risks.   I wanted to change direction a little bit and talk a little bit in the final question about care disparities and CAR T cell. Of course, CAR T-cell therapy is typically offered at large cancer centers and is very expensive. This means that there are issues of access to treatment. In addition, the literature shows us that non-Hispanic Black individuals are twice as likely to develop multiple myeloma compared to their White counterparts. Furthermore, at least right now, Black patients are less likely to receive these novel CAR T-cell therapies and continue to be underrepresented in clinical trials. So, this is a big, complex question, but can you talk a little bit about how outcomes differ between racial and ethnic groups who actually receive CAR T-cell therapy for multiple myeloma? And could you address what you think are the most appropriate strategies for minimizing the disparities in access? Dr. Shaji Kumar: That's a very, very important question, particularly in the context of multiple myeloma, where African American individuals are at a higher risk of getting plasma cell malignancies. I think we need to think about this in the context of what we know about disparities even before the CAR T cell came along. There has been a good amount of literature that has looked at the outcomes based on the types of therapies that could be impacted by this. There have been studies that have looked at cooperative group trials, which often have a good representation of minorities and have shown that if patients have equal access to advanced therapies that we have, their outcomes are comparable or sometimes even better for African American patients compared to Caucasian patients. So I think it's very important that the treatment strategies that we develop are equally accessible to everyone.  In terms of CAR T-cell therapy or immunotherapies, I don't think we have any concrete evidence to suggest that there is any difference in outcomes. And I think it's reasonable to assume that if patients are exposed to similar therapies, they will have similar outcomes, even in the context of immunotherapies. But at the same time, I think we must continue to study this diligently, and the only way to do that is to ensure that clinical trials include patients reflective of society in general. This will allow us to understand if any differences exist. In addition, I think there is a serious risk that with these expensive therapies, this gap can only widen. And I think that is one reason that we must be proactive, particularly with therapies like CAR T-cell therapy, which not only are expensive but also require quite a bit of logistical support for patients to go to larger centers to get these therapies, stay around these larger centers for upwards of a couple of months, which means they are living outside of their usual societal structure, and ensure there is access to the resources that are needed to enable them to do that. So I think there is a lot that is still unknown, but I think we really need to be proactive in ensuring equal access to these therapies. Dr. John Sweetenham: Yes. Thanks for a very thoughtful response to that question, also for the work that you are obviously doing to help address this extremely important issue.  I'd like to thank you for sharing your insights with us today and for the extraordinary work that you're doing and your team are doing to advance care for patients with multiple myeloma. Dr. Shaji Kumar: Thank you, John. Dr. John Sweetenham: And thank you also to our listeners for joining us today. If you value the insights 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 inform. It is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. The guests on this podcast express their own opinions, experience, and conclusions. Guest statements do not necessarily reflect the opinions of ASCO. Mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's guest:    Dr. Shaji Kumar @myelomaMD   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. Shaji Kumar: Consulting or Advisory Role: Takeda, Janssen Oncology, Genentech/Roche, Abbvie, Bristol-Myers Squibb/Celgene, Pfizer, Regeneron, Sanofi, K36 Research Funding (Inst.): Takeda, Abbvie, Novartis, Sanofi, Janssen Oncology, MedImmune, Roche/Genentech, Carsgen Therapeutics Ltd., Allogene Therapeutics, GlaxoSmithKline, Regeneron, Bristol-Myers Squibb/Celgene Travel, Accommodations, Expenses: Abbvie, Pfizer

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/KBV865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until February 17, 2025.Simplifying the Complicated: An Algorithmic Guide for Clinical Decision-Making in HR+, HER2- EBC and MBC In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Lilly.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerErika Hamilton, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcus Biosciences, Inc.; Arvinas, Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Deciphera Pharmaceuticals, Inc.; Ellipses Pharma; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Greenwich LifeSciences, Inc.; iTeos Therapeutics; Janssen Pharmaceuticals, Inc.; Lilly; Loxo Oncology; Mersana Therapeutics; Novartis Pharmaceuticals Corporation; Orum Therapeutics; Pfizer; Relay Therapeutics; Seagen Inc.; and Verascity Science (all paid to institution).Grant/Research Support from AbbVie Inc.; Accutar Biotechnology Inc; Acerta Pharma; ADC Therapeutics SA; Akeso Biopharma Co., Ltd.; Amgen Inc.; Aravive; Artios Pharma; Arvinas, Inc.; AstraZeneca; AtlasMedx, Inc.; BeiGene, Inc.; Black Diamond Therapeutics, Inc.; Bliss Biopharmaceutical (Hangzhou) Co., Ltd.; Boehringer Ingelheim Pharmaceuticals, Inc.; Cascadian Therapeutics; Clovis Oncology; Compugen; Cullinan Oncology, Inc.; Curis, Inc.; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; Dana-Farber Cancer Institute; Dantari; Deciphera Pharmaceuticals, Inc.; Duality Biologics; eFFECTOR Therapeutics, Inc.; Ellipses Pharma; Elucida Oncology, Inc.; EMD Serono, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; FUJIFILM Pharmaceuticals U.S.A., Inc.; G1 Therapeutics, Inc.; H3 Biomedicine Inc.; Harpoon Therapeutics; HUTCHMED (China) Limited; ImmunoGen, Inc.; Immunomedics, Inc.; Incyte; Infinity Pharmaceuticals, Inc.; InvestisBio; Jacobio Pharmaceuticals Group Co., Ltd.; K-Group Beta, Inc.; Karyopharm; Lilly; Loxo Oncology; Lycera; MabSpace Biosciences Co., Ltd.; MacroGenics, Inc.; MedImmune, LLC; Mersana Therapeutics; Merus; Millennium Pharmaceuticals, Inc.; Molecular Templates, Inc.; Novartis Pharmaceuticals Corporation; Nucana; Olema Oncology; OncoMed Pharmaceuticals, Inc.; Onconova Therapeutics; Oncothyreon; ORIC Pharmaceuticals, Inc.; Orinove Inc.; Pfizer; PharmaMar; Pieris Pharmaceuticals, Inc.; Pionyr Immunotherapeutics; Plexxikon; Radius Health, Inc.; Regeneron Pharmaceuticals Inc.; Relay Therapeutics; Repertoire Immune Medicines; Rgenix Inc.; Seagen Inc.; Sermonix Pharmaceuticals; Shattuck Labs Inc.; Stemcentrx, Inc.; Sutro Biopharma, Inc.; Syndax; Syros Pharmaceuticals, Inc.; Taiho Oncology, Inc.; TapImmune Inc; TESARO, Inc.; Tolmar Pharmaceuticals, Inc.; Torque Therapeutics, Inc.; Treadwell Therapeutics; Verastem, Inc.; Vincerx Pharma; zenithepigenetics; and Zymeworks Inc. (all paid to institution).Faculty/PlannerKomal Jhaveri, MD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Blueprint Medicines; Bristol Myers Squibb; Daiichi Sankyo, Inc.; Eisai Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Jounce Therapeutics, Inc.; Lilly/Loxo Oncology; Menarini Group/Stemline Therapeutics; Novartis Pharmaceuticals Corporation; Pfizer; Scorpion Therapeutics; Seattle Genetics, Inc. (Seagen Inc.); Sun Pharma Advanced Research Company; and Taiho Oncology, Inc.Grant/Research Support from ADC Therapeutics SA; AstraZeneca; Blueprint Medicines; Debiopharm; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Novita Pharmaceuticals, Inc.; Pfizer; Puma Biotechnology, Inc.; Scorpion Therapeutics; and Zymeworks Inc.Faculty/PlannerProfessor Stephen Johnston, MA, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Lilly; Novartis Pharmaceuticals Corporation; Pfizer; Puma Biotechnology, Inc.; and Sanofi.Grant/Research Support from AstraZeneca; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Lilly; Novartis Pharmaceuticals Corporation; Pfizer; and Puma Biotechnology, Inc.Speakers Bureau participant with AstraZeneca; Eisai Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; and Pfizer.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/KBV865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until February 17, 2025.Simplifying the Complicated: An Algorithmic Guide for Clinical Decision-Making in HR+, HER2- EBC and MBC In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Lilly.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerErika Hamilton, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcus Biosciences, Inc.; Arvinas, Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Deciphera Pharmaceuticals, Inc.; Ellipses Pharma; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Greenwich LifeSciences, Inc.; iTeos Therapeutics; Janssen Pharmaceuticals, Inc.; Lilly; Loxo Oncology; Mersana Therapeutics; Novartis Pharmaceuticals Corporation; Orum Therapeutics; Pfizer; Relay Therapeutics; Seagen Inc.; and Verascity Science (all paid to institution).Grant/Research Support from AbbVie Inc.; Accutar Biotechnology Inc; Acerta Pharma; ADC Therapeutics SA; Akeso Biopharma Co., Ltd.; Amgen Inc.; Aravive; Artios Pharma; Arvinas, Inc.; AstraZeneca; AtlasMedx, Inc.; BeiGene, Inc.; Black Diamond Therapeutics, Inc.; Bliss Biopharmaceutical (Hangzhou) Co., Ltd.; Boehringer Ingelheim Pharmaceuticals, Inc.; Cascadian Therapeutics; Clovis Oncology; Compugen; Cullinan Oncology, Inc.; Curis, Inc.; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; Dana-Farber Cancer Institute; Dantari; Deciphera Pharmaceuticals, Inc.; Duality Biologics; eFFECTOR Therapeutics, Inc.; Ellipses Pharma; Elucida Oncology, Inc.; EMD Serono, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; FUJIFILM Pharmaceuticals U.S.A., Inc.; G1 Therapeutics, Inc.; H3 Biomedicine Inc.; Harpoon Therapeutics; HUTCHMED (China) Limited; ImmunoGen, Inc.; Immunomedics, Inc.; Incyte; Infinity Pharmaceuticals, Inc.; InvestisBio; Jacobio Pharmaceuticals Group Co., Ltd.; K-Group Beta, Inc.; Karyopharm; Lilly; Loxo Oncology; Lycera; MabSpace Biosciences Co., Ltd.; MacroGenics, Inc.; MedImmune, LLC; Mersana Therapeutics; Merus; Millennium Pharmaceuticals, Inc.; Molecular Templates, Inc.; Novartis Pharmaceuticals Corporation; Nucana; Olema Oncology; OncoMed Pharmaceuticals, Inc.; Onconova Therapeutics; Oncothyreon; ORIC Pharmaceuticals, Inc.; Orinove Inc.; Pfizer; PharmaMar; Pieris Pharmaceuticals, Inc.; Pionyr Immunotherapeutics; Plexxikon; Radius Health, Inc.; Regeneron Pharmaceuticals Inc.; Relay Therapeutics; Repertoire Immune Medicines; Rgenix Inc.; Seagen Inc.; Sermonix Pharmaceuticals; Shattuck Labs Inc.; Stemcentrx, Inc.; Sutro Biopharma, Inc.; Syndax; Syros Pharmaceuticals, Inc.; Taiho Oncology, Inc.; TapImmune Inc; TESARO, Inc.; Tolmar Pharmaceuticals, Inc.; Torque Therapeutics, Inc.; Treadwell Therapeutics; Verastem, Inc.; Vincerx Pharma; zenithepigenetics; and Zymeworks Inc. (all paid to institution).Faculty/PlannerKomal Jhaveri, MD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Blueprint Medicines; Bristol Myers Squibb; Daiichi Sankyo, Inc.; Eisai Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Jounce Therapeutics, Inc.; Lilly/Loxo Oncology; Menarini Group/Stemline Therapeutics; Novartis Pharmaceuticals Corporation; Pfizer; Scorpion Therapeutics; Seattle Genetics, Inc. (Seagen Inc.); Sun Pharma Advanced Research Company; and Taiho Oncology, Inc.Grant/Research Support from ADC Therapeutics SA; AstraZeneca; Blueprint Medicines; Debiopharm; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Novita Pharmaceuticals, Inc.; Pfizer; Puma Biotechnology, Inc.; Scorpion Therapeutics; and Zymeworks Inc.Faculty/PlannerProfessor Stephen Johnston, MA, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Lilly; Novartis Pharmaceuticals Corporation; Pfizer; Puma Biotechnology, Inc.; and Sanofi.Grant/Research Support from AstraZeneca; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Lilly; Novartis Pharmaceuticals Corporation; Pfizer; and Puma Biotechnology, Inc.Speakers Bureau participant with AstraZeneca; Eisai Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; and Pfizer.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/KBV865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until February 17, 2025.Simplifying the Complicated: An Algorithmic Guide for Clinical Decision-Making in HR+, HER2- EBC and MBC In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Lilly.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerErika Hamilton, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcus Biosciences, Inc.; Arvinas, Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Deciphera Pharmaceuticals, Inc.; Ellipses Pharma; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Greenwich LifeSciences, Inc.; iTeos Therapeutics; Janssen Pharmaceuticals, Inc.; Lilly; Loxo Oncology; Mersana Therapeutics; Novartis Pharmaceuticals Corporation; Orum Therapeutics; Pfizer; Relay Therapeutics; Seagen Inc.; and Verascity Science (all paid to institution).Grant/Research Support from AbbVie Inc.; Accutar Biotechnology Inc; Acerta Pharma; ADC Therapeutics SA; Akeso Biopharma Co., Ltd.; Amgen Inc.; Aravive; Artios Pharma; Arvinas, Inc.; AstraZeneca; AtlasMedx, Inc.; BeiGene, Inc.; Black Diamond Therapeutics, Inc.; Bliss Biopharmaceutical (Hangzhou) Co., Ltd.; Boehringer Ingelheim Pharmaceuticals, Inc.; Cascadian Therapeutics; Clovis Oncology; Compugen; Cullinan Oncology, Inc.; Curis, Inc.; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; Dana-Farber Cancer Institute; Dantari; Deciphera Pharmaceuticals, Inc.; Duality Biologics; eFFECTOR Therapeutics, Inc.; Ellipses Pharma; Elucida Oncology, Inc.; EMD Serono, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; FUJIFILM Pharmaceuticals U.S.A., Inc.; G1 Therapeutics, Inc.; H3 Biomedicine Inc.; Harpoon Therapeutics; HUTCHMED (China) Limited; ImmunoGen, Inc.; Immunomedics, Inc.; Incyte; Infinity Pharmaceuticals, Inc.; InvestisBio; Jacobio Pharmaceuticals Group Co., Ltd.; K-Group Beta, Inc.; Karyopharm; Lilly; Loxo Oncology; Lycera; MabSpace Biosciences Co., Ltd.; MacroGenics, Inc.; MedImmune, LLC; Mersana Therapeutics; Merus; Millennium Pharmaceuticals, Inc.; Molecular Templates, Inc.; Novartis Pharmaceuticals Corporation; Nucana; Olema Oncology; OncoMed Pharmaceuticals, Inc.; Onconova Therapeutics; Oncothyreon; ORIC Pharmaceuticals, Inc.; Orinove Inc.; Pfizer; PharmaMar; Pieris Pharmaceuticals, Inc.; Pionyr Immunotherapeutics; Plexxikon; Radius Health, Inc.; Regeneron Pharmaceuticals Inc.; Relay Therapeutics; Repertoire Immune Medicines; Rgenix Inc.; Seagen Inc.; Sermonix Pharmaceuticals; Shattuck Labs Inc.; Stemcentrx, Inc.; Sutro Biopharma, Inc.; Syndax; Syros Pharmaceuticals, Inc.; Taiho Oncology, Inc.; TapImmune Inc; TESARO, Inc.; Tolmar Pharmaceuticals, Inc.; Torque Therapeutics, Inc.; Treadwell Therapeutics; Verastem, Inc.; Vincerx Pharma; zenithepigenetics; and Zymeworks Inc. (all paid to institution).Faculty/PlannerKomal Jhaveri, MD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Blueprint Medicines; Bristol Myers Squibb; Daiichi Sankyo, Inc.; Eisai Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Jounce Therapeutics, Inc.; Lilly/Loxo Oncology; Menarini Group/Stemline Therapeutics; Novartis Pharmaceuticals Corporation; Pfizer; Scorpion Therapeutics; Seattle Genetics, Inc. (Seagen Inc.); Sun Pharma Advanced Research Company; and Taiho Oncology, Inc.Grant/Research Support from ADC Therapeutics SA; AstraZeneca; Blueprint Medicines; Debiopharm; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Novita Pharmaceuticals, Inc.; Pfizer; Puma Biotechnology, Inc.; Scorpion Therapeutics; and Zymeworks Inc.Faculty/PlannerProfessor Stephen Johnston, MA, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Lilly; Novartis Pharmaceuticals Corporation; Pfizer; Puma Biotechnology, Inc.; and Sanofi.Grant/Research Support from AstraZeneca; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Lilly; Novartis Pharmaceuticals Corporation; Pfizer; and Puma Biotechnology, Inc.Speakers Bureau participant with AstraZeneca; Eisai Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; and Pfizer.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/KBV865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until February 17, 2025.Simplifying the Complicated: An Algorithmic Guide for Clinical Decision-Making in HR+, HER2- EBC and MBC In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Lilly.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerErika Hamilton, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcus Biosciences, Inc.; Arvinas, Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Deciphera Pharmaceuticals, Inc.; Ellipses Pharma; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Greenwich LifeSciences, Inc.; iTeos Therapeutics; Janssen Pharmaceuticals, Inc.; Lilly; Loxo Oncology; Mersana Therapeutics; Novartis Pharmaceuticals Corporation; Orum Therapeutics; Pfizer; Relay Therapeutics; Seagen Inc.; and Verascity Science (all paid to institution).Grant/Research Support from AbbVie Inc.; Accutar Biotechnology Inc; Acerta Pharma; ADC Therapeutics SA; Akeso Biopharma Co., Ltd.; Amgen Inc.; Aravive; Artios Pharma; Arvinas, Inc.; AstraZeneca; AtlasMedx, Inc.; BeiGene, Inc.; Black Diamond Therapeutics, Inc.; Bliss Biopharmaceutical (Hangzhou) Co., Ltd.; Boehringer Ingelheim Pharmaceuticals, Inc.; Cascadian Therapeutics; Clovis Oncology; Compugen; Cullinan Oncology, Inc.; Curis, Inc.; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; Dana-Farber Cancer Institute; Dantari; Deciphera Pharmaceuticals, Inc.; Duality Biologics; eFFECTOR Therapeutics, Inc.; Ellipses Pharma; Elucida Oncology, Inc.; EMD Serono, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; FUJIFILM Pharmaceuticals U.S.A., Inc.; G1 Therapeutics, Inc.; H3 Biomedicine Inc.; Harpoon Therapeutics; HUTCHMED (China) Limited; ImmunoGen, Inc.; Immunomedics, Inc.; Incyte; Infinity Pharmaceuticals, Inc.; InvestisBio; Jacobio Pharmaceuticals Group Co., Ltd.; K-Group Beta, Inc.; Karyopharm; Lilly; Loxo Oncology; Lycera; MabSpace Biosciences Co., Ltd.; MacroGenics, Inc.; MedImmune, LLC; Mersana Therapeutics; Merus; Millennium Pharmaceuticals, Inc.; Molecular Templates, Inc.; Novartis Pharmaceuticals Corporation; Nucana; Olema Oncology; OncoMed Pharmaceuticals, Inc.; Onconova Therapeutics; Oncothyreon; ORIC Pharmaceuticals, Inc.; Orinove Inc.; Pfizer; PharmaMar; Pieris Pharmaceuticals, Inc.; Pionyr Immunotherapeutics; Plexxikon; Radius Health, Inc.; Regeneron Pharmaceuticals Inc.; Relay Therapeutics; Repertoire Immune Medicines; Rgenix Inc.; Seagen Inc.; Sermonix Pharmaceuticals; Shattuck Labs Inc.; Stemcentrx, Inc.; Sutro Biopharma, Inc.; Syndax; Syros Pharmaceuticals, Inc.; Taiho Oncology, Inc.; TapImmune Inc; TESARO, Inc.; Tolmar Pharmaceuticals, Inc.; Torque Therapeutics, Inc.; Treadwell Therapeutics; Verastem, Inc.; Vincerx Pharma; zenithepigenetics; and Zymeworks Inc. (all paid to institution).Faculty/PlannerKomal Jhaveri, MD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Blueprint Medicines; Bristol Myers Squibb; Daiichi Sankyo, Inc.; Eisai Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Jounce Therapeutics, Inc.; Lilly/Loxo Oncology; Menarini Group/Stemline Therapeutics; Novartis Pharmaceuticals Corporation; Pfizer; Scorpion Therapeutics; Seattle Genetics, Inc. (Seagen Inc.); Sun Pharma Advanced Research Company; and Taiho Oncology, Inc.Grant/Research Support from ADC Therapeutics SA; AstraZeneca; Blueprint Medicines; Debiopharm; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Novita Pharmaceuticals, Inc.; Pfizer; Puma Biotechnology, Inc.; Scorpion Therapeutics; and Zymeworks Inc.Faculty/PlannerProfessor Stephen Johnston, MA, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Lilly; Novartis Pharmaceuticals Corporation; Pfizer; Puma Biotechnology, Inc.; and Sanofi.Grant/Research Support from AstraZeneca; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Lilly; Novartis Pharmaceuticals Corporation; Pfizer; and Puma Biotechnology, Inc.Speakers Bureau participant with AstraZeneca; Eisai Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; and Pfizer.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

Drs. Shaalan Beg and Rachna Shroff discuss key abstracts on GI cancers that were featured at the 2024 ASCO Gastrointestinal Cancers Symposium, including SKYSCRAPER-08, EMERALD-1, and NEST-1 in esophageal squamous cell carcinoma, hepatocellular carcinoma, and colorectal cancer, respectively. 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 exciting highlights from the 2024 ASCO Gastrointestinal Cancers Symposium. Joining me to discuss some key takeaways from the meeting is the chair of this year's Symposium, Dr. Rachna Shroff. Dr. Shroff is the division chief of Hematology Oncology and chief of GI Medical Oncology at the University of Arizona Cancer Center. She also serves as the associate dean for clinical and translational research at the University of Arizona College of Medicine – Tucson. 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. Shroff, welcome back to the ASCO Daily News Podcast, and congratulations on a great Symposium. The scientific advances and innovative, multidisciplinary approaches that were featured throughout the meeting were really inspiring and reflect the incredible strides we're making in GI cancer research. Dr. Rachna Shroff: Thank you so much for having me back. I am delighted to be here.  Dr. Shaalan Beg: Dr. Shroff, the theme of this year's symposium was "Taking Personalized Care to the Next Level." I'd love to hear your reflections on the sessions that you found most exciting and really resonated with the attendees.  Dr. Rachna Shroff: Yes, thank you. We were really excited about this theme because we really felt that “Taking Personalized Care to the Next Level” translated to thinking through personalized approaches to patient care, not just in the traditional ways that we think of with precision oncology and genomics driving our care, but also how we can think through multidisciplinary approaches and an individualized care plan. Thinking through how artificial intelligence and novel clinical trial designs can and should be implemented to meet the needs of our individual patients. And so we really highlighted that in what was a somewhat new reboot of a session called “Intersections,” which were every day and were really more cross-tumor; they were tumor agnostic but were thematic focused. As I mentioned, those themes were really based on feedback that we had from prior attendees, as well as from the program committee's feeling on what are really the questions that we are dealing with and that are burning in the clinic today and that includes the emerging role of artificial intelligence and machine learning and how we integrate that into our clinical care, approaches to oligometastatic disease, and it's not really just something that we think of in colorectal cancer but haven't fully used that paradigm to really apply it to other GI malignancies. And then the art and science of clinical trial design where, again, traditional randomized phase 3 trials might not be the best and most innovative and most expedient way of bringing novel therapeutics to our patients. And so, I thought that all of those sessions were really highlighting different important topics that we deal with day to day. Additionally, we had a really fantastic keynote lecture from Dr. Kimmie Ng of the Dana-Farber Cancer Institute. She is a world-renowned expert in the early-onset colorectal cancer space, and the timing of her keynote was perfect with the new cancer statistics that came out literally days before GI ASCO that demonstrated this just dramatic rise in early onset GI malignancies as a whole, not just colorectal. And she spoke really in a comprehensive manner not just on clinical approaches, screening approaches, and how to find these patients at an earlier stage, but also kind of gave us a call to action, if you will, in terms of public health initiatives, as well as like I said, clinical care and really thinking outside of the box for how to reach these patients.  And then, of course, we always have what I think is one of my favorite aspects of the meeting, which are the networking opportunities that include the Trainee and Early Career Networking Luncheon, the Women's Networking Reception, and the Meet the Experts Luncheon where, especially as junior career investigators, you have an opportunity to meet what we think of as the “big names” in GI cancer. Dr. Shaalan Beg: Absolutely, I remember my first couple of GI ASCO meetings and those were probably the most memorable sessions that I attended as junior faculty as well.   So let's take a deeper dive into some key abstracts from the meeting. I'd like to begin with Abstract 245. This is the SKYSCRAPER-08 study. It's first-line tiragolumab and atezolizumab with chemotherapy in an Asian patient population with esophageal squamous cell carcinoma. What are your key takeaways from this study?  Dr. Rachna Shroff: Yeah. This was an exciting study in my opinion in the sense that thinking through how we can build on immunotherapy backbones is obviously a pressing question across the GI cancer space. So this was a phase 3 randomized, double-blinded, placebo-controlled trial that looked specifically at patients with esophageal squamous cell carcinomas. And the study was enrolled fully with an Asian population. It looked at taking the traditional chemotherapy backbone and adding to it an anti-PD-L1 with atezolizumab and an anti-TIGIT with tiragolumab. Again, that proof of principle of using anti-TIGIT and PD-L1 has been looked at across a lot of different GI cancer spaces and we know that the esophageal squamous cell cancers tend to be very immunotherapy responsive. So this was a really important question.  This involved a number of patients, a little over 460 patients, who were randomized one-to-one to receive the tiragolumab with atezolizumab with the standard paclitaxel and cisplatin, that's used for esophageal squamous versus chemotherapy alone with placebo. And the primary endpoint was independent review of progression-free survival, and overall survival. And so, out of the 461 patients randomized, there was at the primary analysis, a median improvement in progression free survival, from 5.4 months in the control arm to 6.2 months with a tira-paclitaxel plus chemo arm with a hazard ratio of 0.56, highly statistically significant. Similarly the median overall survival was also improved from 11.1 months to 15.7 months again with a hazard ratio of 0.7 and some of the other key efficacy endpoints were also improved with the addition of the anti-TIGIT PD-L1 approach. And importantly, there was not really safety signals that jumped out at us.  And so, to me, what this means is that, in our patients with esophageal squamous cell carcinoma, we really should be thinking about chemotherapy with immunotherapy as a backbone and how we can build on it. And, you know, I would imagine that it's hard to argue with both the PFS and OS endpoint that adding anti-TIGIT won't necessarily be kind of the new approach to these patients. And importantly, I'll point out that it seems to be a benefit across the subgroups, including PD-1 status, which is always our big question here. I think the only thing to keep in mind is this was an all-Asian population and whether or not that kind of immune profile of the immune responsiveness is different in those patients, but regardless, a positive phase 3 trial. Dr. Shaalan Beg: It's really exciting to see immune checkpoint inhibitors or immunotherapy beyond PD-1 targeted, CTLA-4 targeted treatments making their way into GI Cancers.  Dr. Rachna Shroff: Absolutely. Dr. Shaalan Beg: Sticking with the immunotherapy theme, let's focus on hepatocellular carcinoma. So LBA432, the EMERALD-1 study of transarterial chemoembolization combined with durva with or without bevacizumab looked at people with unresectable hepatocellular carcinoma eligible for embolization. So really a highly anticipated study, I'm wondering what your thoughts are and whether it'll be practice-changing for this field.  Dr. Rachna Shroff: I was excited to see the press release when it showed that the study was positive, and I think it's because now that we're using immunotherapy in the advanced HCC space, our obvious question is, can we integrate it into multimodality approaches? There are a lot of smaller studies looking at neoadjuvant IO approaches, and in this intermediate stage, unresectable hepatocellular carcinoma patients. We wanted to know if there was a utility to liver directed therapy with immunotherapy.  So, this was a large study. It was a global study looking at unresectable HCC with preserved Child-Pugh function. But it was Child-Pugh A and up to B7, importantly. And there were 616 patients randomized in a 1:1:1 fashion, with the control arm being just TACE alone. But then, there was also an opportunity for durvalumab with TACE, as well as durvalumab plus bevacizumab with TACE. The patients would receive durvalumab during their TACE treatments and could receive up to four TACE treatments and then subsequently were either continued on durvalumab alone, durvalumab plus bevacizumab, or the placebo. The primary endpoint was progression-free survival, powered specifically to look at TACE versus durvalumab plus TACE. In this study, the primary endpoint was met with a significant improvement in PFS. Median PFS was 15 months versus 8.2 months, with a hazard ratio of 0.77. Most prespecified subgroups demonstrated this benefit.  Importantly, there was a secondary endpoint looking at durvalumab plus TACE versus TACE alone, and that actually did not show a statistically significant improvement in median PFS from 8.2 months in the control arm to 10.0 months. The overall response rates were slightly higher with the durvalumab plus bevacizumab approach at 43.6%. And importantly in these patients, who oftentimes have a higher burden of disease in the liver, median time to progression is a really important and clinically meaningful endpoint. That was 22 months with the durvalumab plus bevacizumab and TACE versus 10 months for TACE alone. I would just point out that the overall concern we always have with bevacizumab is the increased risk of bleeding and the treatment-related adverse event profile. Overall, there were no safety signals that emerged from this, with nothing that really, especially in that bleeding risk category, jumped out at us. Of course, we haven't seen the overall survival data yet because we have not seen enough follow-up to really see that number.  I do think that this is potentially practice-changing, and I think it just demonstrates that there's probably some synergy between anti-VEGF with anti-PD-1, and then the liver-directed treatments. The obvious question for us in the United States is that the vast majority of people are moving away from TACE and towards more radioembolization and what can we extrapolate from this? Does this really tell us much if people are using more of a Y90-based approach? I think those are a lot of the burning questions that most of us have.  Dr. Shaalan Beg: Yeah, and it's a very interesting direction that the HCC space is taking because we heard in previous meetings, the role of PD-1 inhibition as adjuvant therapy after resection. Now, we have data for local-regionally advanced disease over local-regional treatments. And of course, you already mentioned the data for more advanced disease. So it sounds like immunotherapy may be impacting the management of anyone diagnosed with hepatocellular carcinoma.  Let's talk about the MONET trial, Abstract 249, which compared thoracoscopic esophagectomy and open esophagectomy for thoracic esophageal cancer. Do you think this is a study which may influence the treatment of patients with thoracic esophageal cancer? Dr. Rachna Shroff: So, this was, again, I think, a really important question. It was a randomized, controlled phase 3 trial comparing a more minimally invasive approach with TE — thoracoscopic esophagectomy — versus an open approach. This had patients with clinical stage 1-3, excluding T4 thoracic esophageal squamous cell carcinomas. They were randomized 1:1 to the open versus the TE approach, with a primary endpoint of overall survival and an important secondary endpoint of relapse-free survival. 300 patients were randomized, and at the second planned interim analysis, the median follow-up was a little over two and a half years. The 3-year overall survival was 82% in the TE group versus 70.9% in the open group. The DSMC of this trial actually recommended early termination based on the non-inferiority, which is what they were specifically looking at. There was a very statistically significant one-sided p-value for non-inferiority.  Importantly, the 3-year recurrence-free survival was also markedly better in the TE group versus the open group, with no real notable differences in R0 resection, or a large percentage of patients who needed to be converted from a TE to an open approach, and really not any significant difference in overall postoperative morbidity. I think this just supports the concept that minimally invasive approaches for our patients with GI malignancies can and should be considered. Again, esophageal squamous because they tend to be seen a lot more in Asia, this study was conducted in Japan, but I think that being said, a lot of our surgeons in Europe and in the U.S. are also very amenable to minimally invasive approaches. And I think this just supports the fact that an open approach is not necessary. So, I would think again, that this is something that is implementable and I think will affect the field.  Dr. Shaalan Beg: Moving on to metastatic cholangiocarcinoma, there have been many FGFR inhibitors that have shown activity and promise and are approved for the management of cholangiocarcinoma with FGFR alteration. But at this ASCO GI, we heard the results of the safety and efficacy of an FGFR1, 2, and 3 inhibitor, tinengotinib, as monotherapy for advanced metastatic cholangiocarcinoma (Abstract 434). How do you see this fitting into the broad picture? Dr. Rachna Shroff: Yeah, so this was highly anticipated data, primarily because at this point, the FGFR space in cholangiocarcinoma is quite crowded. And so a lot of us were getting sick of the "me-too" drugs. What is really unique about tinengotinib is that, not only is it a selective multikinase inhibitor, but it also, in preclinical models as well as in early phase one trials, demonstrated potent inhibition of patients with FGFR2 fusions and rearrangements who had acquired resistance mutations. So, as we better understand the first generation of FGFR inhibitors and note the resistance mechanisms, these drugs are now being developed to try to circumvent or overcome those.  This study looked at 4 different cohorts: 1 cohort with FGFR2 fusion patients who had primary progression who never responded to FGFR inhibitors, a second cohort with FGFR2 fusion patients who had progression after primary response, so those with acquired resistance, and then there was non-fusion FGFR alterations because we do know that a number of cholangiocarcinoma patients have other FGFR alterations that are not fusions, and then those with FGFR wild-type. The primary endpoint was objective response rate, with a total of 48 patients enrolled across the four cohorts. And so the 40 patients who were evaluable in the group that had primary resistance, which was the first cohort, there was a response rate was 9.1% and that was partial response, and 31% had tumor reduction with tinengotinib. And similarly in those with acquired resistance, 37.5%, 3 out of 8 patients had a partial response and tumor reductions were noted with an overall disease control rate between those patients with FGFR2 fusions of 94.7%, between those with primary and secondary resistance.  In the patients who had FGFR alterations, there was 3 out of 9 patients with a partial response and again, tumor reductions were notable across the board and the disease control rate was 88.9%. The FGFR wild-type group, not surprisingly, did not see any partial responses, but interestingly, 75% of these patients had at least disease control, and the median progression-free survival was 5.26 months, again, kind of most notably impressive in the 2 cohorts that included FGFR2 fusions. The toxicity profiles are what we come to expect for FGFR inhibitors and we've gotten better at managing those and mitigating some of those so there was really nothing to jump out there. So there is now an ongoing randomized phase III trial specifically looking at tinengotinib versus physician's choice in patients with FGFR2-altered cholangiocarcinoma after having received prior FGFR inhibitors. So that's where I think it's in is for those of us who know that there are multiple drugs in the space, our big question is can we sequence through that? Can we offer multiple FGFR inhibitors in these patients? And I think we are all eagerly anticipating this data as well as the subsequent data to really justify the use of these novel second generation FGFR inhibitors.  Dr. Shaalan Beg: It's been fantastic to see the evolution of these compounds in precision medicine, or precision oncology at its finest, in terms of understanding mechanisms of resistance and treating refractory disease.   Let's focus on colorectal cancer. I'll tell you, there has been a lot of discussion, Dr. Shroff, on social media, on insurance companies sometimes rejecting one biologic or the other based on tumor sidedness. We have talked about tumor sidedness predicting response on this podcast based on data from previous studies. But this year in GI ASCO, Abstract 207 explored the role of tumor genomics and tumor sidedness and they said that it's tumor genomics, that tumor genomics better explains the differences on outcomes, and it explains it better than sidedness. What does this mean to the field? Because a lot of professional organizations have guidelines that are asking people to now incorporate sidedness. So how does that change based on these results? Dr. Rachna Shroff: I really commend these authors on leveraging real-world data, and I think we're getting better and better at recognizing that real world data actually informs our clinical decision making, possibly better than sometimes some of these studies that lead to the guidelines and algorithms that we develop. So this is a perfect example of a little bit cart before horse in trying to understand the way that sidedness and genomics may interplay.   So this was a study that basically leveraged both the Foundation Medicine and Flatiron Health clinical genomic database and looked at patients with microsatellite stable metastatic colorectal cancer. There were a total of 3,845 patients included in a kind of two-thirds one-third split between left sided and right-sided colorectal cancer. And they found the typical genomic alterations that historically have been thought of more with left-sided colorectal cancer like APC and then more of the RAS BRAF alterations in the right-sided patients. But I think what they really thought and what I think was remarkable is they really looked at the patients and how they received chemotherapy with anti-EGFR or bevacizumab therapies, and they did a multivariate analysis to really see what is driving outcomes. And like you mentioned, what they found was patients in the RAS pathway, those classified as having alterations in the RAS pathway, had less favorable outcomes, while those with APC altered group had more favorable outcomes. And that was regardless of treatment received and sidedness.  And so when they did an analysis of what was called a “likelihood ratio test,” they found that when genomics was added to the sidedness evaluation, there was an improvement in outcome prediction, but not when sidedness was added to genomics. Like you said, it kind of demonstrates, at least in this mining of real-world data from Flatiron that tumor genomics is probably a better driver and a more important driver in determining outcomes than sidedness.  I totally agree with you. I would push for us to really kind of bring a little bit of noise to this and to make insurance companies and other companies that are looking at this to think through this a little bit more and make sure that we're putting all of the data together in a comprehensive passion before making the treatment plans and determinations. Dr. Shaalan Beg: The last abstract I'd like to ask you about is Abstract 117, the NEST-1 trial. This study looked at neoadjuvant botensilimab and balstilimab for resectable mismatch repair proficient and deficient colorectal cancer, both MSS and MSI. What are your key takeaways from this study?  Dr. Rachna Shroff: This is another study that is demonstrating that there may potentially be a role for immunotherapy in microsatellite stable patients. I will make the caveat that this was a single-arm study that really was looking at feasibility safety, with efficacy as a secondary endpoint. The combination of bot-bal in the neoadjuvant space for colorectal cancer patients, they received one dose of boten and two fixed doses of bal two weeks apart and then were taken to surgery. They limited the number of patients and out of the 12 patients that were enrolled, they limited the number of mismatch repair deficient patients. So to your point, they allowed both, but they wanted to make sure it was not just MSI-high patients. What they basically found is that it was safe and did not delay surgery or increase risks of adverse events. But importantly, there was significant regression of tumor noted. And some interesting spatial biology analyses demonstrated potentially novel mechanisms of action, especially in the MSS population, and that ctDNA reductions correlated with pathologic response. There were a lot of different things that they were looking at, basically suggesting that bot-bal is safe and can be used in both mismatch repair–deficient and proficient patients with colorectal cancer. And now importantly, they've added some additional cohorts and expanding the study. As I mentioned, this is right now just 12 patients, but does definitely have a provocative result.  Dr. Shaalan Beg: Thanks so much, Dr. Shroff.  Finally, the role of cell-free DNA (cfDNA) in GI cancers has been an exciting and important development in our field. There's tremendous data that emerged at the GI meeting, and we have decided to do a separate ASCO Daily News Podcast dedicated to ctDNA. So listeners, please look out for our coverage of key studies on ctDNA in GI cancers very soon here on the ASCO Daily News Podcast.  Many thanks, Dr. Shroff, for sharing your insights with us today and for your great work in building a robust GI meeting this year. Thank you very much. Dr. Rachna Shroff: Thank you so much. Dr. Shaalan Beg: And thank you to all our listeners for your time today. You'll find links to the abstracts discussed 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. Disclaimer: The purpose of this podcast is to educate and inform. It is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Our guests on this podcast express their own opinions, experiences, and conclusions. These statements do not necessarily reflect the views of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an endorsement by ASCO.   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

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/GHA865. CME/MOC/AAPA credit will be available until January 6, 2025.Mastering the Art of Precision in the Treatment of HR+ Early and Metastatic Breast Cancer: Risk Assessment, Prognostic Testing, and Selection and Sequencing of Therapies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, GRASP, and Living Beyond Breast Cancer. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Lilly, and Olema Pharmaceuticals.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerErika Hamilton, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcus Biosciences, Inc.; Arvinas, Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Deciphera Pharmaceuticals, Inc.; Ellipses Pharma; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Greenwich LifeSciences, Inc.; iTeos Therapeutics; Janssen Pharmaceuticals, Inc.; Lilly; Loxo Oncology; Mersana Therapeutics; Novartis Pharmaceuticals Corporation; Orum Therapeutics; Pfizer; Relay Therapeutics; Seagen Inc.; and Verascity Science (all paid to institution).Grant/Research Support from AbbVie Inc.; Accutar Biotechnology Inc; Acerta Pharma; ADC Therapeutics SA; Akeso Biopharma Co., Ltd.; Amgen Inc.; Aravive; Artios Pharma; Arvinas, Inc.; AstraZeneca; AtlasMedx, Inc.; BeiGene, Inc.; Black Diamond Therapeutics, Inc.; Bliss Biopharmaceutical (Hangzhou) Co., Ltd.; Boehringer Ingelheim Pharmaceuticals, Inc.; Cascadian Therapeutics; Clovis Oncology; Compugen; Cullinan Oncology, Inc.; Curis, Inc.; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; Dana-Farber Cancer Institute; Dantari; Deciphera Pharmaceuticals, Inc.; Duality Biologics; eFFECTOR Therapeutics, Inc.; Ellipses Pharma; Elucida Oncology, Inc.; EMD Serono, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; FUJIFILM Pharmaceuticals U.S.A., Inc.; G1 Therapeutics, Inc.; H3 Biomedicine Inc.; Harpoon Therapeutics; HUTCHMED (China) Limited; ImmunoGen, Inc.; Immunomedics, Inc.; Incyte; Infinity Pharmaceuticals, Inc.; InvestisBio; Jacobio Pharmaceuticals Group Co., Ltd.; K-Group Beta, Inc.; Karyopharm; Lilly; Loxo Oncology; Lycera; MabSpace Biosciences Co., Ltd.; MacroGenics, Inc.; MedImmune, LLC; Mersana Therapeutics; Merus; Millennium Pharmaceuticals, Inc.; Molecular Templates, Inc.; Novartis Pharmaceuticals Corporation; Nucana; Olema Oncology; OncoMed Pharmaceuticals, Inc.; Onconova Therapeutics; Oncothyreon; ORIC Pharmaceuticals, Inc.; Orinove Inc.; Pfizer; PharmaMar; Pieris Pharmaceuticals, Inc.; Pionyr Immunotherapeutics; Plexxikon; Radius Health, Inc.; Regeneron Pharmaceuticals Inc.; Relay Therapeutics; Repertoire Immune Medicines; Rgenix Inc.; Seagen Inc.; Sermonix Pharmaceuticals; Shattuck Labs Inc.; Stemcentrx, Inc.; Sutro Biopharma, Inc.; Syndax; Syros Pharmaceuticals, Inc.; Taiho Oncology, Inc.; TapImmune Inc; TESARO, Inc.; Tolmar Pharmaceuticals, Inc.; Torque Therapeutics, Inc.; Treadwell Therapeutics; Verastem, Inc.; Vincerx Pharma; zenithepigenetics; and Zymeworks Inc. (all paid to institution).Faculty/PlannerKomal Jhaveri, MD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Blueprint Medicines; Bristol Myers Squibb; Daiichi Sankyo, Inc.; Eisai Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Jounce Therapeutics, Inc.; Lilly/Loxo Oncology; Menarini Group/Stemline Therapeutics; Novartis Pharmaceuticals Corporation; Pfizer; Scorpion Therapeutics; Seattle Genetics, Inc. (Seagen Inc.); Sun Pharma Advanced Research Company; and Taiho Oncology, Inc.Grant/Research Support from ADC Therapeutics SA; AstraZeneca; Blueprint Medicines; Debiopharm; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Novita Pharmaceuticals, Inc.; Pfizer; Puma Biotechnology, Inc.; Scorpion Therapeutics; and Zymeworks Inc.Faculty/PlannerHope S. Rugo, MD, FASCO, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Daiichi Sankyo, Inc.; Mylan/Viatris Inc.; Napo Pharmaceuticals, Inc.; and Puma Biotechnology, Inc.Grant/Research Support from AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; OBI Pharma, Inc.; Pfizer; Pionyr Immunotherapeutics; Sermonix Pharmaceuticals; and Stemline Therapeutics.Faculty/PlannerPaolo Tarantino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Daiichi Sankyo, Inc.; Gilead Sciences, Inc.; and Lilly.Grant/Research Support from AstraZeneca.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/GHA865. CME/MOC/AAPA credit will be available until January 6, 2025.Mastering the Art of Precision in the Treatment of HR+ Early and Metastatic Breast Cancer: Risk Assessment, Prognostic Testing, and Selection and Sequencing of Therapies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, GRASP, and Living Beyond Breast Cancer. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Lilly, and Olema Pharmaceuticals.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerErika Hamilton, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcus Biosciences, Inc.; Arvinas, Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Deciphera Pharmaceuticals, Inc.; Ellipses Pharma; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Greenwich LifeSciences, Inc.; iTeos Therapeutics; Janssen Pharmaceuticals, Inc.; Lilly; Loxo Oncology; Mersana Therapeutics; Novartis Pharmaceuticals Corporation; Orum Therapeutics; Pfizer; Relay Therapeutics; Seagen Inc.; and Verascity Science (all paid to institution).Grant/Research Support from AbbVie Inc.; Accutar Biotechnology Inc; Acerta Pharma; ADC Therapeutics SA; Akeso Biopharma Co., Ltd.; Amgen Inc.; Aravive; Artios Pharma; Arvinas, Inc.; AstraZeneca; AtlasMedx, Inc.; BeiGene, Inc.; Black Diamond Therapeutics, Inc.; Bliss Biopharmaceutical (Hangzhou) Co., Ltd.; Boehringer Ingelheim Pharmaceuticals, Inc.; Cascadian Therapeutics; Clovis Oncology; Compugen; Cullinan Oncology, Inc.; Curis, Inc.; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; Dana-Farber Cancer Institute; Dantari; Deciphera Pharmaceuticals, Inc.; Duality Biologics; eFFECTOR Therapeutics, Inc.; Ellipses Pharma; Elucida Oncology, Inc.; EMD Serono, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; FUJIFILM Pharmaceuticals U.S.A., Inc.; G1 Therapeutics, Inc.; H3 Biomedicine Inc.; Harpoon Therapeutics; HUTCHMED (China) Limited; ImmunoGen, Inc.; Immunomedics, Inc.; Incyte; Infinity Pharmaceuticals, Inc.; InvestisBio; Jacobio Pharmaceuticals Group Co., Ltd.; K-Group Beta, Inc.; Karyopharm; Lilly; Loxo Oncology; Lycera; MabSpace Biosciences Co., Ltd.; MacroGenics, Inc.; MedImmune, LLC; Mersana Therapeutics; Merus; Millennium Pharmaceuticals, Inc.; Molecular Templates, Inc.; Novartis Pharmaceuticals Corporation; Nucana; Olema Oncology; OncoMed Pharmaceuticals, Inc.; Onconova Therapeutics; Oncothyreon; ORIC Pharmaceuticals, Inc.; Orinove Inc.; Pfizer; PharmaMar; Pieris Pharmaceuticals, Inc.; Pionyr Immunotherapeutics; Plexxikon; Radius Health, Inc.; Regeneron Pharmaceuticals Inc.; Relay Therapeutics; Repertoire Immune Medicines; Rgenix Inc.; Seagen Inc.; Sermonix Pharmaceuticals; Shattuck Labs Inc.; Stemcentrx, Inc.; Sutro Biopharma, Inc.; Syndax; Syros Pharmaceuticals, Inc.; Taiho Oncology, Inc.; TapImmune Inc; TESARO, Inc.; Tolmar Pharmaceuticals, Inc.; Torque Therapeutics, Inc.; Treadwell Therapeutics; Verastem, Inc.; Vincerx Pharma; zenithepigenetics; and Zymeworks Inc. (all paid to institution).Faculty/PlannerKomal Jhaveri, MD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Blueprint Medicines; Bristol Myers Squibb; Daiichi Sankyo, Inc.; Eisai Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Jounce Therapeutics, Inc.; Lilly/Loxo Oncology; Menarini Group/Stemline Therapeutics; Novartis Pharmaceuticals Corporation; Pfizer; Scorpion Therapeutics; Seattle Genetics, Inc. (Seagen Inc.); Sun Pharma Advanced Research Company; and Taiho Oncology, Inc.Grant/Research Support from ADC Therapeutics SA; AstraZeneca; Blueprint Medicines; Debiopharm; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Novita Pharmaceuticals, Inc.; Pfizer; Puma Biotechnology, Inc.; Scorpion Therapeutics; and Zymeworks Inc.Faculty/PlannerHope S. Rugo, MD, FASCO, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Daiichi Sankyo, Inc.; Mylan/Viatris Inc.; Napo Pharmaceuticals, Inc.; and Puma Biotechnology, Inc.Grant/Research Support from AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; OBI Pharma, Inc.; Pfizer; Pionyr Immunotherapeutics; Sermonix Pharmaceuticals; and Stemline Therapeutics.Faculty/PlannerPaolo Tarantino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Daiichi Sankyo, Inc.; Gilead Sciences, Inc.; and Lilly.Grant/Research Support from AstraZeneca.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/GHA865. CME/MOC/AAPA credit will be available until January 6, 2025.Mastering the Art of Precision in the Treatment of HR+ Early and Metastatic Breast Cancer: Risk Assessment, Prognostic Testing, and Selection and Sequencing of Therapies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, GRASP, and Living Beyond Breast Cancer. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Lilly, and Olema Pharmaceuticals.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerErika Hamilton, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcus Biosciences, Inc.; Arvinas, Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Deciphera Pharmaceuticals, Inc.; Ellipses Pharma; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Greenwich LifeSciences, Inc.; iTeos Therapeutics; Janssen Pharmaceuticals, Inc.; Lilly; Loxo Oncology; Mersana Therapeutics; Novartis Pharmaceuticals Corporation; Orum Therapeutics; Pfizer; Relay Therapeutics; Seagen Inc.; and Verascity Science (all paid to institution).Grant/Research Support from AbbVie Inc.; Accutar Biotechnology Inc; Acerta Pharma; ADC Therapeutics SA; Akeso Biopharma Co., Ltd.; Amgen Inc.; Aravive; Artios Pharma; Arvinas, Inc.; AstraZeneca; AtlasMedx, Inc.; BeiGene, Inc.; Black Diamond Therapeutics, Inc.; Bliss Biopharmaceutical (Hangzhou) Co., Ltd.; Boehringer Ingelheim Pharmaceuticals, Inc.; Cascadian Therapeutics; Clovis Oncology; Compugen; Cullinan Oncology, Inc.; Curis, Inc.; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; Dana-Farber Cancer Institute; Dantari; Deciphera Pharmaceuticals, Inc.; Duality Biologics; eFFECTOR Therapeutics, Inc.; Ellipses Pharma; Elucida Oncology, Inc.; EMD Serono, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; FUJIFILM Pharmaceuticals U.S.A., Inc.; G1 Therapeutics, Inc.; H3 Biomedicine Inc.; Harpoon Therapeutics; HUTCHMED (China) Limited; ImmunoGen, Inc.; Immunomedics, Inc.; Incyte; Infinity Pharmaceuticals, Inc.; InvestisBio; Jacobio Pharmaceuticals Group Co., Ltd.; K-Group Beta, Inc.; Karyopharm; Lilly; Loxo Oncology; Lycera; MabSpace Biosciences Co., Ltd.; MacroGenics, Inc.; MedImmune, LLC; Mersana Therapeutics; Merus; Millennium Pharmaceuticals, Inc.; Molecular Templates, Inc.; Novartis Pharmaceuticals Corporation; Nucana; Olema Oncology; OncoMed Pharmaceuticals, Inc.; Onconova Therapeutics; Oncothyreon; ORIC Pharmaceuticals, Inc.; Orinove Inc.; Pfizer; PharmaMar; Pieris Pharmaceuticals, Inc.; Pionyr Immunotherapeutics; Plexxikon; Radius Health, Inc.; Regeneron Pharmaceuticals Inc.; Relay Therapeutics; Repertoire Immune Medicines; Rgenix Inc.; Seagen Inc.; Sermonix Pharmaceuticals; Shattuck Labs Inc.; Stemcentrx, Inc.; Sutro Biopharma, Inc.; Syndax; Syros Pharmaceuticals, Inc.; Taiho Oncology, Inc.; TapImmune Inc; TESARO, Inc.; Tolmar Pharmaceuticals, Inc.; Torque Therapeutics, Inc.; Treadwell Therapeutics; Verastem, Inc.; Vincerx Pharma; zenithepigenetics; and Zymeworks Inc. (all paid to institution).Faculty/PlannerKomal Jhaveri, MD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Blueprint Medicines; Bristol Myers Squibb; Daiichi Sankyo, Inc.; Eisai Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Jounce Therapeutics, Inc.; Lilly/Loxo Oncology; Menarini Group/Stemline Therapeutics; Novartis Pharmaceuticals Corporation; Pfizer; Scorpion Therapeutics; Seattle Genetics, Inc. (Seagen Inc.); Sun Pharma Advanced Research Company; and Taiho Oncology, Inc.Grant/Research Support from ADC Therapeutics SA; AstraZeneca; Blueprint Medicines; Debiopharm; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Novita Pharmaceuticals, Inc.; Pfizer; Puma Biotechnology, Inc.; Scorpion Therapeutics; and Zymeworks Inc.Faculty/PlannerHope S. Rugo, MD, FASCO, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Daiichi Sankyo, Inc.; Mylan/Viatris Inc.; Napo Pharmaceuticals, Inc.; and Puma Biotechnology, Inc.Grant/Research Support from AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; OBI Pharma, Inc.; Pfizer; Pionyr Immunotherapeutics; Sermonix Pharmaceuticals; and Stemline Therapeutics.Faculty/PlannerPaolo Tarantino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Daiichi Sankyo, Inc.; Gilead Sciences, Inc.; and Lilly.Grant/Research Support from AstraZeneca.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/GHA865. CME/MOC/AAPA credit will be available until January 6, 2025.Mastering the Art of Precision in the Treatment of HR+ Early and Metastatic Breast Cancer: Risk Assessment, Prognostic Testing, and Selection and Sequencing of Therapies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, GRASP, and Living Beyond Breast Cancer. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Lilly, and Olema Pharmaceuticals.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerErika Hamilton, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcus Biosciences, Inc.; Arvinas, Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Deciphera Pharmaceuticals, Inc.; Ellipses Pharma; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Greenwich LifeSciences, Inc.; iTeos Therapeutics; Janssen Pharmaceuticals, Inc.; Lilly; Loxo Oncology; Mersana Therapeutics; Novartis Pharmaceuticals Corporation; Orum Therapeutics; Pfizer; Relay Therapeutics; Seagen Inc.; and Verascity Science (all paid to institution).Grant/Research Support from AbbVie Inc.; Accutar Biotechnology Inc; Acerta Pharma; ADC Therapeutics SA; Akeso Biopharma Co., Ltd.; Amgen Inc.; Aravive; Artios Pharma; Arvinas, Inc.; AstraZeneca; AtlasMedx, Inc.; BeiGene, Inc.; Black Diamond Therapeutics, Inc.; Bliss Biopharmaceutical (Hangzhou) Co., Ltd.; Boehringer Ingelheim Pharmaceuticals, Inc.; Cascadian Therapeutics; Clovis Oncology; Compugen; Cullinan Oncology, Inc.; Curis, Inc.; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; Dana-Farber Cancer Institute; Dantari; Deciphera Pharmaceuticals, Inc.; Duality Biologics; eFFECTOR Therapeutics, Inc.; Ellipses Pharma; Elucida Oncology, Inc.; EMD Serono, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; FUJIFILM Pharmaceuticals U.S.A., Inc.; G1 Therapeutics, Inc.; H3 Biomedicine Inc.; Harpoon Therapeutics; HUTCHMED (China) Limited; ImmunoGen, Inc.; Immunomedics, Inc.; Incyte; Infinity Pharmaceuticals, Inc.; InvestisBio; Jacobio Pharmaceuticals Group Co., Ltd.; K-Group Beta, Inc.; Karyopharm; Lilly; Loxo Oncology; Lycera; MabSpace Biosciences Co., Ltd.; MacroGenics, Inc.; MedImmune, LLC; Mersana Therapeutics; Merus; Millennium Pharmaceuticals, Inc.; Molecular Templates, Inc.; Novartis Pharmaceuticals Corporation; Nucana; Olema Oncology; OncoMed Pharmaceuticals, Inc.; Onconova Therapeutics; Oncothyreon; ORIC Pharmaceuticals, Inc.; Orinove Inc.; Pfizer; PharmaMar; Pieris Pharmaceuticals, Inc.; Pionyr Immunotherapeutics; Plexxikon; Radius Health, Inc.; Regeneron Pharmaceuticals Inc.; Relay Therapeutics; Repertoire Immune Medicines; Rgenix Inc.; Seagen Inc.; Sermonix Pharmaceuticals; Shattuck Labs Inc.; Stemcentrx, Inc.; Sutro Biopharma, Inc.; Syndax; Syros Pharmaceuticals, Inc.; Taiho Oncology, Inc.; TapImmune Inc; TESARO, Inc.; Tolmar Pharmaceuticals, Inc.; Torque Therapeutics, Inc.; Treadwell Therapeutics; Verastem, Inc.; Vincerx Pharma; zenithepigenetics; and Zymeworks Inc. (all paid to institution).Faculty/PlannerKomal Jhaveri, MD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Blueprint Medicines; Bristol Myers Squibb; Daiichi Sankyo, Inc.; Eisai Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Jounce Therapeutics, Inc.; Lilly/Loxo Oncology; Menarini Group/Stemline Therapeutics; Novartis Pharmaceuticals Corporation; Pfizer; Scorpion Therapeutics; Seattle Genetics, Inc. (Seagen Inc.); Sun Pharma Advanced Research Company; and Taiho Oncology, Inc.Grant/Research Support from ADC Therapeutics SA; AstraZeneca; Blueprint Medicines; Debiopharm; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Novita Pharmaceuticals, Inc.; Pfizer; Puma Biotechnology, Inc.; Scorpion Therapeutics; and Zymeworks Inc.Faculty/PlannerHope S. Rugo, MD, FASCO, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Daiichi Sankyo, Inc.; Mylan/Viatris Inc.; Napo Pharmaceuticals, Inc.; and Puma Biotechnology, Inc.Grant/Research Support from AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; OBI Pharma, Inc.; Pfizer; Pionyr Immunotherapeutics; Sermonix Pharmaceuticals; and Stemline Therapeutics.Faculty/PlannerPaolo Tarantino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Daiichi Sankyo, Inc.; Gilead Sciences, Inc.; and Lilly.Grant/Research Support from AstraZeneca.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/GHA865. CME/MOC/AAPA credit will be available until January 6, 2025.Mastering the Art of Precision in the Treatment of HR+ Early and Metastatic Breast Cancer: Risk Assessment, Prognostic Testing, and Selection and Sequencing of Therapies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, GRASP, and Living Beyond Breast Cancer. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Lilly, and Olema Pharmaceuticals.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerErika Hamilton, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcus Biosciences, Inc.; Arvinas, Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Deciphera Pharmaceuticals, Inc.; Ellipses Pharma; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Greenwich LifeSciences, Inc.; iTeos Therapeutics; Janssen Pharmaceuticals, Inc.; Lilly; Loxo Oncology; Mersana Therapeutics; Novartis Pharmaceuticals Corporation; Orum Therapeutics; Pfizer; Relay Therapeutics; Seagen Inc.; and Verascity Science (all paid to institution).Grant/Research Support from AbbVie Inc.; Accutar Biotechnology Inc; Acerta Pharma; ADC Therapeutics SA; Akeso Biopharma Co., Ltd.; Amgen Inc.; Aravive; Artios Pharma; Arvinas, Inc.; AstraZeneca; AtlasMedx, Inc.; BeiGene, Inc.; Black Diamond Therapeutics, Inc.; Bliss Biopharmaceutical (Hangzhou) Co., Ltd.; Boehringer Ingelheim Pharmaceuticals, Inc.; Cascadian Therapeutics; Clovis Oncology; Compugen; Cullinan Oncology, Inc.; Curis, Inc.; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; Dana-Farber Cancer Institute; Dantari; Deciphera Pharmaceuticals, Inc.; Duality Biologics; eFFECTOR Therapeutics, Inc.; Ellipses Pharma; Elucida Oncology, Inc.; EMD Serono, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; FUJIFILM Pharmaceuticals U.S.A., Inc.; G1 Therapeutics, Inc.; H3 Biomedicine Inc.; Harpoon Therapeutics; HUTCHMED (China) Limited; ImmunoGen, Inc.; Immunomedics, Inc.; Incyte; Infinity Pharmaceuticals, Inc.; InvestisBio; Jacobio Pharmaceuticals Group Co., Ltd.; K-Group Beta, Inc.; Karyopharm; Lilly; Loxo Oncology; Lycera; MabSpace Biosciences Co., Ltd.; MacroGenics, Inc.; MedImmune, LLC; Mersana Therapeutics; Merus; Millennium Pharmaceuticals, Inc.; Molecular Templates, Inc.; Novartis Pharmaceuticals Corporation; Nucana; Olema Oncology; OncoMed Pharmaceuticals, Inc.; Onconova Therapeutics; Oncothyreon; ORIC Pharmaceuticals, Inc.; Orinove Inc.; Pfizer; PharmaMar; Pieris Pharmaceuticals, Inc.; Pionyr Immunotherapeutics; Plexxikon; Radius Health, Inc.; Regeneron Pharmaceuticals Inc.; Relay Therapeutics; Repertoire Immune Medicines; Rgenix Inc.; Seagen Inc.; Sermonix Pharmaceuticals; Shattuck Labs Inc.; Stemcentrx, Inc.; Sutro Biopharma, Inc.; Syndax; Syros Pharmaceuticals, Inc.; Taiho Oncology, Inc.; TapImmune Inc; TESARO, Inc.; Tolmar Pharmaceuticals, Inc.; Torque Therapeutics, Inc.; Treadwell Therapeutics; Verastem, Inc.; Vincerx Pharma; zenithepigenetics; and Zymeworks Inc. (all paid to institution).Faculty/PlannerKomal Jhaveri, MD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Blueprint Medicines; Bristol Myers Squibb; Daiichi Sankyo, Inc.; Eisai Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Jounce Therapeutics, Inc.; Lilly/Loxo Oncology; Menarini Group/Stemline Therapeutics; Novartis Pharmaceuticals Corporation; Pfizer; Scorpion Therapeutics; Seattle Genetics, Inc. (Seagen Inc.); Sun Pharma Advanced Research Company; and Taiho Oncology, Inc.Grant/Research Support from ADC Therapeutics SA; AstraZeneca; Blueprint Medicines; Debiopharm; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Novita Pharmaceuticals, Inc.; Pfizer; Puma Biotechnology, Inc.; Scorpion Therapeutics; and Zymeworks Inc.Faculty/PlannerHope S. Rugo, MD, FASCO, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Daiichi Sankyo, Inc.; Mylan/Viatris Inc.; Napo Pharmaceuticals, Inc.; and Puma Biotechnology, Inc.Grant/Research Support from AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; OBI Pharma, Inc.; Pfizer; Pionyr Immunotherapeutics; Sermonix Pharmaceuticals; and Stemline Therapeutics.Faculty/PlannerPaolo Tarantino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Daiichi Sankyo, Inc.; Gilead Sciences, Inc.; and Lilly.Grant/Research Support from AstraZeneca.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/GHA865. CME/MOC/AAPA credit will be available until January 6, 2025.Mastering the Art of Precision in the Treatment of HR+ Early and Metastatic Breast Cancer: Risk Assessment, Prognostic Testing, and Selection and Sequencing of Therapies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, GRASP, and Living Beyond Breast Cancer. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Lilly, and Olema Pharmaceuticals.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerErika Hamilton, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcus Biosciences, Inc.; Arvinas, Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Deciphera Pharmaceuticals, Inc.; Ellipses Pharma; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Greenwich LifeSciences, Inc.; iTeos Therapeutics; Janssen Pharmaceuticals, Inc.; Lilly; Loxo Oncology; Mersana Therapeutics; Novartis Pharmaceuticals Corporation; Orum Therapeutics; Pfizer; Relay Therapeutics; Seagen Inc.; and Verascity Science (all paid to institution).Grant/Research Support from AbbVie Inc.; Accutar Biotechnology Inc; Acerta Pharma; ADC Therapeutics SA; Akeso Biopharma Co., Ltd.; Amgen Inc.; Aravive; Artios Pharma; Arvinas, Inc.; AstraZeneca; AtlasMedx, Inc.; BeiGene, Inc.; Black Diamond Therapeutics, Inc.; Bliss Biopharmaceutical (Hangzhou) Co., Ltd.; Boehringer Ingelheim Pharmaceuticals, Inc.; Cascadian Therapeutics; Clovis Oncology; Compugen; Cullinan Oncology, Inc.; Curis, Inc.; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; Dana-Farber Cancer Institute; Dantari; Deciphera Pharmaceuticals, Inc.; Duality Biologics; eFFECTOR Therapeutics, Inc.; Ellipses Pharma; Elucida Oncology, Inc.; EMD Serono, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; FUJIFILM Pharmaceuticals U.S.A., Inc.; G1 Therapeutics, Inc.; H3 Biomedicine Inc.; Harpoon Therapeutics; HUTCHMED (China) Limited; ImmunoGen, Inc.; Immunomedics, Inc.; Incyte; Infinity Pharmaceuticals, Inc.; InvestisBio; Jacobio Pharmaceuticals Group Co., Ltd.; K-Group Beta, Inc.; Karyopharm; Lilly; Loxo Oncology; Lycera; MabSpace Biosciences Co., Ltd.; MacroGenics, Inc.; MedImmune, LLC; Mersana Therapeutics; Merus; Millennium Pharmaceuticals, Inc.; Molecular Templates, Inc.; Novartis Pharmaceuticals Corporation; Nucana; Olema Oncology; OncoMed Pharmaceuticals, Inc.; Onconova Therapeutics; Oncothyreon; ORIC Pharmaceuticals, Inc.; Orinove Inc.; Pfizer; PharmaMar; Pieris Pharmaceuticals, Inc.; Pionyr Immunotherapeutics; Plexxikon; Radius Health, Inc.; Regeneron Pharmaceuticals Inc.; Relay Therapeutics; Repertoire Immune Medicines; Rgenix Inc.; Seagen Inc.; Sermonix Pharmaceuticals; Shattuck Labs Inc.; Stemcentrx, Inc.; Sutro Biopharma, Inc.; Syndax; Syros Pharmaceuticals, Inc.; Taiho Oncology, Inc.; TapImmune Inc; TESARO, Inc.; Tolmar Pharmaceuticals, Inc.; Torque Therapeutics, Inc.; Treadwell Therapeutics; Verastem, Inc.; Vincerx Pharma; zenithepigenetics; and Zymeworks Inc. (all paid to institution).Faculty/PlannerKomal Jhaveri, MD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Blueprint Medicines; Bristol Myers Squibb; Daiichi Sankyo, Inc.; Eisai Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Jounce Therapeutics, Inc.; Lilly/Loxo Oncology; Menarini Group/Stemline Therapeutics; Novartis Pharmaceuticals Corporation; Pfizer; Scorpion Therapeutics; Seattle Genetics, Inc. (Seagen Inc.); Sun Pharma Advanced Research Company; and Taiho Oncology, Inc.Grant/Research Support from ADC Therapeutics SA; AstraZeneca; Blueprint Medicines; Debiopharm; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Novita Pharmaceuticals, Inc.; Pfizer; Puma Biotechnology, Inc.; Scorpion Therapeutics; and Zymeworks Inc.Faculty/PlannerHope S. Rugo, MD, FASCO, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Daiichi Sankyo, Inc.; Mylan/Viatris Inc.; Napo Pharmaceuticals, Inc.; and Puma Biotechnology, Inc.Grant/Research Support from AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; OBI Pharma, Inc.; Pfizer; Pionyr Immunotherapeutics; Sermonix Pharmaceuticals; and Stemline Therapeutics.Faculty/PlannerPaolo Tarantino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Daiichi Sankyo, Inc.; Gilead Sciences, Inc.; and Lilly.Grant/Research Support from AstraZeneca.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

Drs. Neeraj Agarwal and Jeanny Aragon-Ching discuss several key abstracts to be presented at the 2024 ASCO GU Cancers Symposium, including sequencing versus upfront combination therapies for mCRPC in the BRCAAway study, updates on the CheckMate-9ER and CheckMate-214 trials in ccRCC, and a compelling real-world retrospective study in mUC of patients with FGFR2 and FGFR3 mutations. TRANSCRIPT Dr. Neeraj Agarwal: Hello, everyone, and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, your guest host of the podcast today. I am the director of the Genitourinary Oncology Program and a professor of medicine at the University of Utah's Huntsman Cancer Institute, and editor-in-chief of ASCO Daily News. I am delighted to welcome Dr. Jeanny Aragon-Ching, a genitourinary oncologist and the clinical program director of Genitourinary Cancers at the Inova Schar Cancer Institute in Virginia. Today, we will be discussing key posters and oral abstracts that will be featured at the 2024 ASCO Genitourinary Cancer Symposium, which is celebrating 20 years of evolution in GU oncology this year.  You will find our full disclosures in the transcript of this podcast, and disclosures of all guests on the podcast at asco.org/DNpod.  Jeanny, it's great to have you on the podcast today to highlight some key abstracts for our listeners ahead of the GU meeting. Dr. Jeanny Aragon-Ching: Thank you so much, Neeraj. It's an honor to be here. Dr. Neeraj Agarwal: Jeanny, as you know, this year we are celebrating the 20th anniversary of the ASCO GU Cancers Symposium, and judging from this year's abstracts, it's clear that this meeting continues to play a major role in advancing GU cancer research. Dr. Jeanny Aragon-Ching: Indeed, Neeraj. This year's abstracts reflect the important strides we have made in GU cancers. So, let's start with the prostate cancer abstracts. What is your takeaway from Abstract 19 on BRCAAway, which will be presented by Dr. Maha Hussein, and of which you are a co-author? As our listeners know, several PARP inhibitor combinations with second-generation androgen receptor pathway inhibitors, or ARPIs, have recently been approved as first-line treatment for patients with metastatic castrate-resistant prostate cancer, or metastatic CRPC, and the question of sequencing PARP inhibitors and ARPIs instead of combining them has emerged. From that perspective, the results of the BRCAAway trial are very important. Can you tell us a little bit more about this abstract, Neeraj?  Dr. Neeraj Agarwal: I totally agree with you, Jeanny. The BRCAAway study attempts to answer the crucial questions regarding sequencing versus upfront combination of therapies in the mCRPC setting. It is a phase 2 trial of abiraterone versus olaparib versus abiraterone with olaparib in patients with mCRPC harboring homologous recombination repair mutations. Enrolled patients had mCRPC disease and no prior exposure to PARP inhibitors or ARPIs or chemotherapy in the mCRPC setting and had BRCA1 or BRCA2 or ATM mutations. As previously mentioned, these patients were randomized to 3 arms: abiraterone monotherapy at 1000 milligrams once daily, or olaparib monotherapy at 300 milligrams twice daily, or the combination of abiraterone and olaparib. The primary endpoint was progression-free survival per RECIST 1.1 or Prostate Cancer Working Group 3-based criteria or clinical assessment or death, so, whichever occurred first was deemed to be progression.   Secondary endpoints included measurable disease response rates, PSA response rate, and toxicity. This was a relatively small trial with 21 patients in the combination arm, 19 patients in the abiraterone monotherapy arm, and 21 patients in the olaparib monotherapy arm. It should be noted that 26% of patients had received docetaxel chemotherapy in the hormone-sensitive setting, and only 3% of patients had any prior exposure to an ARPI, and these were darolutamide or enzalutamide or in the non-metastatic CRPC setting.  The results are very interesting. The median progression-free survival was 39 months in the combination arm, while it was 8.4 months in the abiraterone arm and 14 months in the olaparib arm. An important finding that I would like to highlight is that crossover was also allowed in the monotherapy arms. Of the 19 patients receiving abiraterone, 8 crossed over to receive olaparib, and of the 21 patients receiving olaparib, 8 crossed over to the abiraterone arm. The median PFS from randomization was 16 months in both groups of patients who received abiraterone followed by olaparib or those who received olaparib followed by abiraterone. This is striking when compared to 39 months in patients who started therapy with the combination therapy of abiraterone with olaparib. Dr. Jeanny Aragon-Ching: Thank you so much for that wonderful summary, Neeraj. So the key message from this abstract is that combining olaparib and abiraterone upfront seems to be associated with improvement in PFS compared to just sequencing those agents. Dr. Neeraj Agarwal: Exactly, Jeanny. I would like to add that these results are even more important given that in real-world practice, only half of the patients with mCRPC receive a second-line treatment. Based on these results, upfront intensification with a combination of an ARPI plus a PARP inhibitor in the first-line mCRPC setting seems to have superior efficacy compared to sequencing of these agents. Dr. Jeanny Aragon-Ching: Thank you so much. Now, moving on to a different setting in prostate cancer, there were a couple of abstracts assessing transperineal biopsy compared to the conventional transrectal biopsy for the detection of prostate cancer. So let's start with Abstract 261. Neeraj, can you tell us a little bit more about this abstract? Dr. Neeraj Agarwal: Sure, Jeanny. So, in Abstract 261 titled "Randomized Trial of Transperineal versus Transrectal Prostate Biopsy to Prevent Infection Complications," Dr. Jim Hugh and colleagues led a multicenter randomized trial comparing these 2 approaches, so, transperineal biopsy without antibiotic prophylaxis with transrectal biopsy with targeted prophylaxis in patients with suspected prostate cancer. The primary outcome was post-biopsy infection. Among the 567 participants included in the intention-to-treat analysis, no infection was reported with the transperineal approach, while 4 were detected with the transrectal approach, with a p-value of 0.059. The rates of other complications, such as urinary retention and significant bleeding, were very low and similar in both groups. The investigators also found that detection of clinically significant cancer was similar between the 2 techniques and concluded that the transperineal approach is more likely to reduce the risk of infection without antibiotic prophylaxis. Dr. Jeanny Aragon-Ching: So the key takeaway from this abstract sounds like office-based transperineal biopsy is well-tolerated and does not compromise cancer detection, along with better antibiotic stewardship and health care cost benefits.  Moving on to Abstract 273, also comparing these two approaches, what would be your key takeaway message, Neeraj?  Dr. Neeraj Agarwal: In this Abstract 273, titled "Difference in High-Risk Prostate Cancer Detection between Transrectal and Transperineal Approaches," Dr. Semko and colleagues found that the transperineal biopsy based on MRI fusion techniques was also characterized by a higher possibility of detecting high-risk prostate cancer and other risk factors as well, such as perineural and lymphovascular invasion or the presence of cribriform pattern, compared to the conventional transrectal method. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. So we can see that the transperineal approach is gaining more importance and could be associated with more benefits compared to the conventional methods.   Let's now switch gears to kidney cancer, Neeraj. Dr. Neeraj Agarwal: Sure, Jeanny. Let's start by highlighting Abstract 361, which discusses patient-reported outcomes of the LITESPARK-005 study. So what can you tell us about this abstract, Jeanny?  Dr. Jeanny Aragon-Ching: Thank you, Neeraj. So as a reminder to our listeners, based on the LITESPARK-005 trial, it was a Phase 3 trial looking at belzutifan, which is an inhibitor of hypoxia inducible factor 2 alpha or I'll just call HIF-2 alpha for short, was very recently approved by the FDA as a second-line treatment option for patients with advanced or metastatic clear cell renal cell carcinoma after prior progression on immune checkpoint and antiangiogenic therapies. The title of Abstract 361 is "Belzutifan versus Everolimus in Patients with Previously Treated Advanced RCC: Patient-Reported Outcomes in the Phase 3 LITESPARK-005 Study," and this will be presented by Dr. Tom Pells at the meeting. At a median follow-up of 25.7 months, the median duration of treatment with belzutifan was 7.6 months, while it was only 3.9 months with everolimus. At the time of data cutoff date for the second interim analysis, 22.6% of patients remained on belzutifan while only 5% remained on everolimus. In the quality of life questionnaires, the time of deterioration to various quality of life scores, as assessed by standardized scales, was significantly longer in patients randomized to the belzutifan arm compared to those in the everolimus arm. Also, patients in the everolimus arm had worse physical functioning scores. Dr. Neeraj Agarwal: Yes, Jeanny. In addition to the improved outcomes associated with belzutifan, patient-reported outcomes indicate better disease-specific symptoms and better quality of life among patients treated with belzutifan compared to everolimus. This is great news for patients with advanced renal cell carcinoma.  Now, Jeanny, can you please tell us about the two abstracts that reported longer follow-up of CheckMate 9ER and CheckMate 214 trials in untreated patients with advanced or metastatic renal cell carcinoma? Dr. Jeanny Aragon-Ching: Yes, Neeraj. So you are referring to Abstracts 362 and 363. Let's start with Abstract 362. This abstract reports the results after a median follow-up of 55 months in the CheckMate 9ER trial, comparing the combination of nivolumab and cabozantinib to sunitinib in patients with advanced RCC without any prior treatment, so first-line therapy. The primary endpoint was PFS per RECIST 1.1 as assessed by an independent central review. So there were key secondary outcomes including overall survival (OS), objective response rates, and safety. Consistent with prior analysis at a median follow-up time of 18.1 and 44 months, the combination of nivolumab and cabozantinib at a median follow up of 55.6 months continues to show a significant reduction in the risk of progression or death by 42% and in the risk of death by 23% compared to sunitinib.  Dr. Neeraj Agarwal: And Jeanny, what can you tell us about the efficacy results of this combination by IMDC risk categories? Dr. Jeanny Aragon-Ching: Similar to prior results in patients with intermediate to poor risk IMDC risk category, the combination treatment maintained significant efficacy and reduced the risk of progression or death by 44% and the risk of death by 27%. To put it simply, the update now shows a 15-month improvement in overall survival with the cabozantinib-nivolumab combination compared to sunitinib, which is amazing. Also, in patients with favorable IMDC risk group, which represented truly a small number of patients in the trial, there was a strong trend for improvement of outcomes as well. I would like to point out that no new safety concerns were identified. Dr. Neeraj Agarwal: So, it looks like the key message from this abstract is that with longer follow-up, the combination of nivolumab and cabozantinib maintains a meaningful long-term efficacy benefit over sunitinib, supporting its use for newly diagnosed patients with advanced or metastatic renal cell carcinoma.   Let's move on to Abstract 363, which compares nivolumab with ipilimumab to sunitinib in first-line advanced renal cell carcinoma. What would you like to tell us about this abstract, Jeanny? Dr. Jeanny Aragon-Ching: Yes, Neeraj. The title of this abstract is "Nivolumab plus Ipilimumab versus Sunitinib for the First-Line Treatment of Advanced RCC: Long-Term Follow-Up Data from the Phase 3 CheckMate 214 Trial." In this abstract, Dr. Tannir and colleagues report outcomes with the longest median follow-up in first-line advanced RCC setting for any clinical trial. So the median follow-up now is about 18 months. The primary endpoints were OS, PFS, and objective response rates, as assessed by an independent review according to RECIST 1.1 criteria in the intermediate to poor risk IMDC risk group, which is the intent-to-treat (ITT) analysis, while secondary outcomes included the same outcomes in the ITT population of patients. Although the progression-free survival was similar in both arms, the combination of nivolumab-ipilimumab reduced the risk of death by 28% compared to sunitinib in the ITT population of patients. When stratifying the results by IMDC risk groups, the combination arm of nivolumab-ipilimumab showed significant improvement in the intermediate to poor risk group, but there was no difference in the favorable risk group. But in the study, no new safety signals were identified. Dr. Neeraj Agarwal: Thank you, Jeanny, for such a comprehensive description of the results of these two studies. I'd like to add that the median overall survival of patients with metastatic renal cell carcinoma in the ITT population in the CheckMate 214 trial has now reached 53 months, which would have been unimaginable just a decade ago. This is wonderful news for our patients. So the key takeaway from these two abstracts would be that immune checkpoint inhibitor-based combinations remain the backbone of first-line advanced renal cell carcinoma treatment.  Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. This is wonderful news for all of our patients, especially for those who are being treated for first-line therapy.  Now, let's move on to the bladder cancer abstracts. We have two exciting abstracts from the UNITE database. What are your insights on Abstract 537, titled "Outcomes in Patients with Advanced Urethral Carcinoma Treated with Enfortumab Vedotin After Switch-Maintenance of Avelumab in the UNITE Study"? Dr. Neeraj Agarwal: As our listeners know, enfortumab vedotin is an antibody-drug conjugate that binds to a protein called Nectin 4 expressed on bladder cancer cells. In this abstract, Dr. Amanda Nizam and colleagues describe outcomes in 49 patients receiving third-line enfortumab vedotin after prior progression on platinum-based therapy and maintenance avelumab. At a median follow-up of 8.5 months, the median progression-free survival was 7 months and the median overall survival was 13.3 months with enfortumab vedotin in this treatment-refractory setting, the objective response rates were 54%. The message of this study is that enfortumab vedotin is an effective salvage therapy regimen for those patients who have already progressed on earlier lines of therapies, including platinum-based and immunotherapy regimens. Dr. Jeanny Aragon-Ching: Thank you, Neeraj, for that comprehensive review.  I want to focus on another patient population in the UNITE database, which is the use of fibroblast growth factor receptor (FGFR) alterations. Can you tell us more about the sequencing now of erdafitinib and enfortumab vedotin in these patients with metastatic urothelial cancer, as discussed in Abstract 616? Dr. Neeraj Agarwal: Sure, Jeanny. As a reminder, erdafitinib is a fibroblast growth factor receptor kinase inhibitor approved for patients with locally advanced or metastatic urothelial carcinoma harboring FGFR2 or FGFR3 alterations after progression on platinum-based chemotherapy. However, the optimal sequencing of therapies in these patients is unclear, especially with enfortumab vedotin being approved in the salvage therapy setting and now in the frontline therapy setting.  So in this retrospective study, all patients with metastatic urothelial carcinoma had FGFR2 or FGFR3 alterations. Dr. Cindy Jiang and colleagues report outcomes in 24 patients receiving enfortumab vedotin after erdafitinib, 15 patients receiving erdafitinib after enfortumab vedotin, and 55 patients receiving enfortumab vedotin only. This is a multicenter national study. Interestingly, patients receiving both agents had a longer overall survival in a multivariate analysis, regardless of the treatment sequencing, than patients receiving enfortumab vedotin alone or only with a hazard ratio of 0.52. The objective response rate of enfortumab vedotin in the enfortumab vedotin monotherapy arm was 49%. When these agents were sequenced, the objective response with enfortumab vedotin was 32% after erdafitinib and 67% when used before erdafitinib. Dr. Jeanny Aragon-Ching: Thank you so much, Neeraj. I think these are important real-world data results, but I would like to point out that larger and prospective studies are still needed to confirm these findings, especially regarding the outcome of erdafitinib after enfortumab vedotin, particularly when the latter is used in the first-line setting. Dr. Neeraj Agarwal: I totally agree, Jeanny. Now, let's discuss some abstracts related to disparities in the management of patients with genitourinary cancers.  Dr. Jeanny Aragon-Ching: Sure, actually, I would like to discuss 2 abstracts related to disparities in patients with prostate cancer. So the first one, Abstract 265, titled "Patient-Provider Rurality and Outcomes in Older Men with Prostate Cancer." In this study, Dr. Stabellini, Dr. Guha and the team used a SEER Medicare-linked database that included more than 75,000 patients with prostate cancer. The primary outcome was all-cause mortality, with secondary outcomes included prostate cancer-specific mortality. The investigators showed that the all-cause mortality risk was 44% higher in patients with prostate cancer from rural areas who had a provider from a non-metropolitan area compared to those who were in a metropolitan area and had a provider also from a metropolitan area. Dr. Neeraj Agarwal: Those are very important data and highlight the healthcare disparities among the rural population with prostate cancer that still exist.  So what is your key takeaway from Abstract 267, titled "Rural-Urban Disparities in Prostate Cancer Survival," which is a population-based study? Dr. Jeanny Aragon-Ching: Of course. This abstract discusses, actually, a very similar issue regarding access to healthcare among rural versus urban patients. In this study, Dr. Hu and Hashibe and colleagues and team at the Huntsman Cancer Institute assessed all-cause death and prostate cancer-related death risk in a retrospective study in which patients with prostate cancer based on rural versus urban residencies looked at 18,000 patients diagnosed with prostate cancer between 2004 and 2017. 15% lived in rural counties. Similar to the prior abstract we talked about, patients living in rural areas had about a 19% higher risk of all-cause mortality and a 21% higher risk of prostate cancer-specific mortality in comparison to patients living in urban areas. Dr. Neeraj Agarwal: So Jeanny, we can say that both of these abstracts, led by different groups of investigators, highlight that patients with prostate cancer living in rural areas have inferior survival outcomes compared to those living in urban areas, and it is time to focus on the disparities experienced by the rural population with prostate cancer.  Dr. Jeanny Aragon-Ching: Yeah, absolutely Neeraj. I concur with your thoughts.  So, any final thoughts before we wrap up the podcast today? Dr. Neeraj Agarwal: Yes, before concluding, Jeanny, I want to express my gratitude for your participation and the valuable insights you have shared today. Your contributions are always appreciated, and I sincerely thank you for taking the time to join us today.   As we bring this podcast to a close, I would like to highlight the significant advances happening in the treatment of patients with genitourinary cancers during our upcoming 2024 ASCO GU meeting. Many studies featuring practice-impacting data will be presented by investigators from around the globe. I encourage our listeners to not only participate at this event to celebrate these achievements, but to also play a role in disseminating these cutting-edge findings to practitioners worldwide. By doing so, we can collectively maximize the benefit for patients around the world.  And thank you to our listeners for joining us today. You will find links to 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 very much.  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. Guest speakers express their own opinions, experience, and conclusions. Guest statements on the podcast do not necessarily reflect 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. Neeraj Agarwal  @neerajaiims  Dr. Jeanny Aragon-Ching    Follow ASCO on social media:     @ASCO on Twitter     ASCO on Facebook     ASCO on LinkedIn       Disclosures:      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. Jeanny Aragon-Ching:    Honoraria: Bristol-Myers Squibb, EMD Serono, Astellas Scientific and Medical Affairs Inc., Pfizer/EMD Serono  Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant, Exelixis,   Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb, Astellas/Seattle Genetics. 

In this episode of BioTalk with Rich Bendis, we're joined by three guests from Solaxa: CEO & Founder Christian Walker, Chief Operating Officer Luis T. Gutierrez, Jr., and Chief Commercial Officer Jennifer Butler. Solaxa is a pioneering biotech company with a mission to revolutionize the treatment of cerebellar ataxias and acute nerve injuries caused by trauma and chemotherapy.   Discover the compelling story behind Solaxa's choice to establish its roots in Montgomery County and how the BioHealth Capital Region has played a crucial role in its growth. Learn how Solaxa's team was assembled, including the inspiring success stories of Luis and Jennifer, both part of the BioHealth Innovation and Montgomery County Maryland's Executive in Residence program.   Hear how Solaxa is making a difference in the world of neurology with SLX-001, a drug showing immense promise in treating cerebellar ataxias. Dive into their innovative approach, including the development of their treatment for cerebellar ataxias.   Additionally, discover how Solaxa's pioneering efforts in this field provide hope for healing. Join us for an enlightening discussion on the future of neurology, innovative treatments, and the remarkable journey of Solaxa.   CEO & Founder Christian Walker has focused his last twenty years pursuing the commercialization of nerve injury solutions. Christian's fundraising experience spans raising money for start-ups, being a start-up venture capitalist, and securing significant non-dilutive financing through grants. At Christian's prior start-ups, Christian was directly responsible for securing $11M in venture financing.   While at Toucan Capital, he served as Principal of a $140 million venture capital fund focused on early-stage investments in stem cells and regenerative medicine. At Johns Hopkins and Walter Reed, he helped secure $22.5M in non-dilutive grants.   Luis T. Gutierrez, Jr. serves as Chief Operating Officer of Solaxa while also serving as an Executive in Residence with BioHealth Innovation.   In both roles, he leverages his 25+ years of expertise in helping novel medical technologies with scientific and clinical promise transition to becoming successful commercial enterprises.    He previously served in executive roles with Veranex, Theralink Technologies, Aptiv Solutions, and Covance.   Chief Commercial Officer Jennifer Butler has 25 years of broad biotechnology industry experience. Her commercial roles at MedImmune, AstraZeneca, and Innate have equipped her with a deep understanding of commercial execution at large and emerging biopharma. Notably, Jen launched Innate's first commercial product in a rare oncology population. Jennifer also is also serving as an Executive in Residence with BioHealth Innovation.  

Synopsis: Brett Hall, Ph.D., is the CSO of Immuneering, a public, clinical-stage oncology company dedicated to developing medicines for broad populations of cancer patients by applying its deep knowledge of translational bioinformatics to every stage of the drug development process. Brett talks about his background in the military targeting nuclear missiles prior to becoming a scientist and some of the commonalities between working in the military and pharma/biotech. He shares his thoughts on AI and machine learning in drug development. He talks about Immuneering's disease-agnostic platform that enables the company to utilize human data, novel biology and chemistry, and translational planning to create and advance its pipeline. Finally, he discusses their focus on oncology and providing potential treatments for patients with advanced solid tumors. Biography: Brett Hall, Ph.D. has served as Chief Scientific Officer of Immuneering since November 2019. He also served as the Founder and Chairman of the board of directors of BioArkive, Inc., or BioArkive, a privately held biotechnology services company from January 2019 until December 2021. Prior to joining Imuneering, Dr. Hall served as the Chief Executive Officer of Asellus Therapeutics, LLC from July 2015 until May 2018. Dr. Hall served in roles of increasing responsibility with Johnson & Johnson from November 2008 until July 2014, culminating in his role as the Head of Biomarkers of the Hematologic Disease Area Stronghold, where he led translational efforts for Sylvant® and Imbruvica® through clinical development. Subsequently, he served as the Head of Translational Medicine of Oncology at Medimmune, LLC, the biologics division of AstraZeneca Pharmaceuticals LP, from July 2014 until July 2015, before transitioning to executive discovery roles in biotechnology. He has extensive drug development and leadership experience ranging from early drug discovery through translational clinical sciences, including multiple drug registrations. Dr. Hall has extensively published in the areas of tumor microenvironment (TME) and translational sciences, and holds multiple patents for drug pharmacology and discovery. He was also a tenure-track Assistant Professor at Ohio State University where his laboratory focused on the development of human TME-aligned models to better translate preclinical data into the clinic and discover novel biomarkers. Prior to Dr. Hall's career in life sciences, he served in the United States Air Force and worked as an investment banker. Dr. Hall received his B.S. in biochemistry from Ohio State University, his Ph.D. in immunology and cancer biology from West Virginia University, and completed his post-doctoral fellowship in cancer cell epigenetics at St. Jude Children's Research Hospital.

Drs. Shaalan Beg and Priyanka Kanth discuss the readiness, logistics, and barriers to implementing universal germline multigene panel testing for colorectal cancer (CRC) following new guidelines from the National Comprehensive Cancer Network that recommend genomic testing for all individuals with CRC younger than age 50. The experts also address other areas of unmet needs as new data emerge on moderate-risk genes and their association with CRC. 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 the vice president of oncology at Science 37 and an adjunct associate professor at UT Southwestern Medical Center in Dallas. Last year, the National Comprehensive Cancer Network, or NCCN, updated its guidelines on colorectal cancer (CRC), recommending that all patients with colorectal cancer who receive a diagnosis before the age of 50 have multigene panel testing and that multigene testing should also be considered for patients 50 years of age and older with colorectal cancer, regardless of a personal or family history or other criteria. This represents a huge paradigm shift in the screening and care of patients with inherited cancers. And today, I'm joined by Dr. Priyanka Kanth, an associate professor of medicine and the director of the GI Cancer Prevention Program at MedStar Georgetown University Hospital in Washington, DC, to discuss new research that explores the readiness, logistics, and barriers associated with the implementation of universal germline testing in clinical practice.  You'll find our full disclosures in the transcript of this episode, and disclosures of all guests on the podcast are available at asco.org/DNpod. Dr. Kanth, it's great to have you on the podcast today. Dr. Priyanka Kanth: Thank you, Dr. Beg. It's wonderful to be here today and discuss this very exciting topic. Dr. Shaalan Beg: As a gastroenterologist who sees patients and families with a high risk for GI cancer, including medically underserved populations, can you comment on the significance of the expanded NCCN guidelines for colorectal cancer? Dr. Priyanka Kanth: Yes, absolutely. So this is, I would say, a big change from NCCN recommending pretty much every colorectal cancer patient can undergo multigene panel testing or universal. So everyone who's younger than age 50 and has colon cancer should get multigene panel testing. But we are also expanding it to pretty much anyone who may have colorectal cancer, and we can offer multigene panel testing. So, we are broadening the pool of patients who can get tested, and this will bring in more patients from very different demographics. So I think it will expand to every arena of patients with different insurance profiles, underserved, and, as more insurance companies and Medicare/Medicaid picks up, I think this will help a lot more patients in not only following on their genetic testing, but also their family members.  Dr. Shaalan Beg: Medical oncologists are very familiar with the challenges of implementing somatic molecular testing for people who have cancer. I can only imagine that implementing universal germline testing also has significant logistical challenges and barriers. You recently published a study in JCO Precision Oncology along with your colleagues and captured some interesting perspectives from clinicians on their practice of implementing universal genomic testing for colorectal cancer. Can you tell us more about this? Dr. Priyanka Kanth: Absolutely. So I would first like to thank the lead authors and senior authors of this study. They are Linda Rodgers-Fouche and Sanjeevani Arora and Rachel Hodan, who literally wrote the study and created and did all the legwork. And as you know how hard it is to do these big survey studies, so really thank them.  The study is a cross-sectional survey of the members of this Community Collaborative Group of America, IGC, which I would say comprises a lot of genetic counselors, gastroenterologists, oncologists, and colorectal surgeons who take care of these patients. So these are highly specialized groups that work in the field of GI genetics. Roughly 300 plus members were sent the survey to get their take on how they think [multigene panel testing] can be implemented for all colorectal cancer patients.   So to give you a synopsis of the study, the majority of members who participated, 70% or more, they supported this universal germline testing for colorectal cancer patients. But interestingly, more than 50% also thought that it will require a change in their practice or how this will be delivered. So that's the major takeaway, I would say. We are all supportive but how to really deliver to the patient would be the biggest challenge or barrier for us in the future.  Dr. Shaalan Beg: So, your study reported concerns on knowledge among non-genetics providers. I would assume that includes a lot of clinicians who are the first people to be in contact with potential patients who would require testing. How can the field mitigate this problem? And what are some alternate delivery service models for increasing awareness and making the process of ordering and following up on the results more efficient for practices? Dr. Priyanka Kanth: We all know the biggest barrier I would say is resources like who's going to deliver the added pool of patients that get genetic testing. So most of the current scenario, they're all seen by genetic counselors, but we have a limited number of genetic counselors and they cannot truly deal with this big influx. So how to educate non-genetic providers would be the biggest barrier. But also implementing in the system itself, like can we do pretest counseling as the first contact with the patient to deliver to discuss like you should undergo genetic testing. So that contact, can that be done with a non-genetic provider or even by other modes like telemedicine? Or can we do something like an online chat box or something which could just not only go over all the types of testing but opens the door for the patient to ask questions. So if there are alternate modes of delivery where the pretest is taken care of, that would be one big change required.   The other part is like when the test is done, who returns the results? So where does it go and who explains the results? So at that point, we surely need more genetic and even non-genetic providers if they are comfortable. So how to educate them would be the biggest barrier. At that point, I think, we are still figuring out the biggest change is in the system and requiring a take from all the stakeholders who are part of taking care of these patients. So not only genetic counselors, but oncologists, gastroenterologists, pathologists who are taking care of this patient to be on board and have a really clear-cut flow of how these are delivered, how these results are returned, and how they are explained to family members. Dr. Shaalan Beg: The workflows and the resources that you have in a high-risk GI clinic at a center like Georgetown's, I think it's safe to say, are much more than what typical resources a practicing provider will have in the clinic. How do you envision clinics resourcing for this type of test either through training or retraining their existing staff or by adding additional resources?  Dr. Shaalan Beg: At the community setting, it is really hard to educate essentially everyone as well. So, I feel like taking the load off the genetic counselor at the pretest level is the biggest implementation or change that can be done. And if we can remove that because not every patient is going to be positive for the gene mutation either; it does filter many patients who eventually will need returns. So at that place, how do you implement and where do you implement is the key and it is so system-based that I cannot even pinpoint. But I agree, bigger academic centers have better advantages and a knowledge base as compared to smaller community cancer centers or practices. Dr. Priyanka Kanth: Yeah, and I noticed that many of the respondents in your survey agreed with offering multigene panels, but there was variability by profession, and I was wondering if that resonated with you and that was an expected finding or not. Dr. Priyanka Kanth: Yes, and it was more so in terms of standardized multigene panel versus customized panel. So, this is fairly understandable because the genetic counselor is so well versed in offering which genes should be tested based on family history, but a non-genetic provider may not be fully equipped with the knowledge. So for example, myself, I do GI genetics, but if I have a patient with a lot of breast cancer in the family, I do defer them to a high-risk breast team. So there are nuances, too. The major difference here was also in standardized multigene panel, most of the gastroenterologists, oncologists were all for it compared to customized, which were more heavily leaned by the genetic counselor based on family history. And I can see why it's different because standardized, I would say, is much easier to implement and compared to customizing, which is based on family history or other cancer history and family. That's the major difference in the study. It comes down to education and experience and the follow-up based on what comes back from it.   Dr. Shaalan Beg: You've highlighted many factors, both from the pre-test, sort of preparing and selecting the right individuals, to ordering the right test based on the participant's risk factor profile and then optimal ways of following up on the results of these genomic tests. What are other areas of unmet needs when it comes to genomic testing for colorectal cancer? Dr. Priyanka Kanth: We know a lot about high-risk genes that are associated with colorectal cancer. We still are finding and learning about many genes, many moderate-risk genes, and their association with colorectal cancer. We don't have enough data or long-term cohort data to understand how they truly affect their lifetime risk for colorectal cancer and how do we truly surveil these patients. So that's one of the big barriers. Genetics still cannot explain all colorectal cancers. So as we get more data, we may discover more things and more genes that may be associated. But understanding these moderate-risk genes and their association with colorectal cancer would be, I think, one of the key areas to be looked into in the future. Dr. Shaalan Beg: And I would imagine as new biomarkers are identified, there will need to be a strategy to retest people who may have had genomic testing in the past. Dr. Priyanka Kanth: Absolutely. We are already encountering that in a practice. I have patients who have been tested maybe 10 years ago and just had Lynch mutation tested and were negative for that or so, and now we have so many other genes which are associated and also to understand family history changes. So, as family history changes, there might be clues to say that, “Okay, we should expand the panel or we should add these patients.” So it is a very dynamic situation. There could be a scenario in which we have a lot of patients who may need to be retested based on their current situation or even based on changing family history and the availability of genetic information. So, when I see a patient, I also tell them if we don't find anything or we are not doing anything major, we say, “Let's regroup in 3 to 5 years, let's see where we are,” or even with the risk mutation for some of the moderate-risk genes, we may change in a few years. So, revisiting that with these patients is highly useful. Dr. Shaalan Beg: So, is it safe to say that as of 2023, if we're seeing people in our clinic who have not had testing in the last 3 to 5 years, that they should have a discussion for repeat testing today? Dr. Priyanka Kanth: Yes, in terms of certain, I would say, newer polyposis genes in the GI world that have been included, some other moderate gene mutation which we have a little bit more sense of now and it has not been tested, I think that can be expanded. Five years is a safe bet. Last 2 to 3 years, maybe not so much, but you can revisit this. Also, some patients were tested for a smaller gene panel. So not 2 genes, but maybe 10 genes were included. That would probably still stand true. They may not need 70 gene panels, so it's still good to review that in the current scenario, and every few years, every 5 years, I would say.   Dr. Shaalan Beg: Whenever I think about any type of new test that has logistical challenges, has costs associated with it, and has operational demands of the clinic, I think about its disparate effect across different populations based on race, ethnicity, geography, demographics. Can you talk a little bit about how these guideline changes, what type of impact they may have, positive or not, for comprehensive genomic testing for colorectal cancer across different populations?  Dr. Priyanka Kanth: Yes, I think this is more positive than negative. This will include more patients and include more family members who were not being included, who were being missed. As we know that one of the reasons to do this multigene panel testing was the criteria, the family history criteria or the risk prediction models are not perfect. And the recent studies have shown that not every family member, every patient, is going to fit in these criteria. So we are getting more and more data in recent years that I think the much better, long-term option is to do a multi-chain panel and find it because we are missing patients. So it will increase the pool [of patients to be tested], and that will surely increase patients from all demographics. And as we do it more, there will be more buy-in from the payers and hopefully, this will decrease disparity. The problem, I think the negative part is how do we deliver it to everyone? If it is there but we are not able to deliver and that there is disparity on who gets the test and who does not, then that will create another disparity in a sense that it's there and we could have used it, but it's not being delivered. So the pros are we can include everyone, but how to include everyone is the big question. Dr. Shaalan Beg: So, Dr. Kanth, there are indeed challenges ahead in our pursuit for universal germline testing for colorectal cancer. I'd like to thank you for sharing your valuable insights with us today on the ASCO Daily News Podcast.   Dr. Priyanka Kanth: Thank you very much for having me here. It was great to talk to you, Dr. Beg. Dr. Shaalan Beg: And thank you to our listeners for your time today. Finally, if you value the insights that you hear on the 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, 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. Priyanka Kanth @priyanka_kanth   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. Priyanka Kanth:  Patents, Royalties, Other Intellectual Property: Methods and Compositions for Predicting a Colon Cancer Subtype

William H. Sauer, MD, FHRS, CCDS, of Brigham and Women's Hospital is joined by guests Erik Andrews, MD, MPH, and Christian Thomas Ruff, MD, MPH, of Brigham and Women's Hospital to discuss Safety of Switching from a Vitamin K Antagonist to a Non-Vitamin K Antagonist Oral Anticoagulant in Frail Older Patients with Atrial Fibrillation: Results of the FRAIL-AF Randomized Controlled Trial. In the FRAIL-AF clinical trial, there were more bleeding events when elderly patients were switched from warfarin to rivaroxaban, apixaban, edoxaban, or dabigatran.   https://www.hrsonline.org/education/TheLead https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.123.066485   Host Disclosure(s): W. Sauer: Honoraria/Speaking/Consulting Fee: Biotronik, Biosense Webster, Inc., Abbott, Boston Scientific; Research (Contracted Grants for PIs Named Investigators Only): Medtronic   Contributor Disclosure(s): E. Andrews: No relevant financial relationships with ineligible companies to disclose.  C. Ruff: Honoraria/Speaking/Consulting Fee: Bayer Healthcare Pharmaceuticals, Janssen Pharmaceuticals, Daiichi, Boehringer Ingelheim, Bristol-Myers Squibb, Portola Pharmaceuticals; Research (Contracted Grants for PIs Named Investigators Only): Daiichi, MedImmune

Sharon L. Tasman is a seasoned business and technology attorney with over 30 years of legal experience. Having spent 15 years at Hogan Lovells, one of the world's largest law firms, and serving as in-house counsel at MedImmune, Sharon founded HTBiz Law to offer clients the best of both worlds—a boutique law firm experience with the expertise of a global firm.For more info, visit shrimptankpodcast.com/atlanta/Check us out on Facebook: www.facebook.com/theshrimptankFollow us on Twitter: twitter.com/theshrimptank?lang=enCheck out Atlanta on LinkedIn: www.linkedin.com/showcase/shrimp-tank-episodes

It seems this country has become numb to the Opioid Crisis. We can not bury our heads, mandate it away, or think it only happens to bad people. Hopefully, it won't take a personal tragedy in someone's life to understand that this crosses all demographics. We have had Hamilton on before to discuss his alcohol use disorder, but today he will tell us how a back surgery led him to a long relationship with opioids. Let's stop stigmatizing this crisis and come together for solutions as this affects everyone.Hamilton Baiden is Youturn Health's CEO. Prior to joining Youturn Health, Hamilton was Executive Vice President of Sales at Avella Specialty Pharmacy where he oversaw the growth of the business from a small regional pharmacy to the largest independent specialty pharmacy in the nation. His knowledge and understanding of the pharmacy industry were developed throughout his professional career, working in various roles for prominent pharmaceutical manufacturing companies, including MedImmune, Serono, Daiichi, and Sanofi. A graduate of The Citadel in Charleston, SC, with strong ties to his community, Hamilton served as Chairman of the Board of Directors for a nonprofit organization dedicated to animal welfare, Altered Tails, and currently serves on the National Board of the American Liver Foundation Southwest Division. Hamilton is also in recovery and committed to helping others.

Respiratory Syncytial Virus (RSV) is a potentially deadly virus that tragically causes an estimated 100 to 300 deaths each year among children younger than age 5. Children from families with low-income status, children of color and children with compromised immune systems are at particular risk. Join us for a discussion about the recent progress in making mAbs available for the upcoming RSV season and next steps that are needed to ensure that all children are covered. Moderator Adjoa Kyerematen, MS Vice President of Public Affairs & Communications National Minority Quality Forum Adjoa Kyerematen is Vice President of Public Affairs and Communications at the National Minority Quality Forum (NMQF), the leading research national nonprofit focused on health equity and advancing minority health. Adjoa co-chairs the Cancer Stage Shifting Initiative, NMQF's initiative aligned with President Biden's Cancer Moonshot 2.0 program, and leads strategic campaigns that shape policy, execute community interventions, and drives awareness to advance cancer equity. Adjoa was named to PRWeek's 40 under 40 top PR Professionals and a Capitol Hill/federal government agency veteran, Adjoa is a strategic communications expert with an award-winning record and health equity expertise. Prior to this, Adjoa worked at CMS' Center for Innovation (CMMI) as a Senior Advisor in the center's leadership office where she crafted messaging, advised on communication efforts and stakeholder engagement among payers, pharmaceutical companies, health systems and other federal agencies. She currently serves on the Patient-Centered Outcomes Research Institute (PCORI) Advisory Panel on Clinical Effectiveness and Decision Science (CEDS) which analyzes critical knowledge gaps in health communication particularly in vulnerable communities. Panelists Erin E. Jones, JD Director, Legislative and Strategy Counsel March of Dimes Office of Government Affairs Erin Jones currently serves as the Director, Legislative and Strategy Counsel within March of Dimes Office of Government Affairs. Erin has been with the organization for 17 years. With more than 28 years of experience in health care, behavioral health, advocacy, and public policy, Erin has held various positions within March of Dimes and as Interim Director of Behavioral Health at Eastern CT Health Network, Medicaid Outreach and Advocacy Director for MAXIMUS and the State of Connecticut, Counselor and Case Manager at Easter Seals of Connecticut. Erin earned her Bachelor's degree in Sociology from Saint Joseph's College, her Master's degree of science in Clinical and Counseling Psychology at Central Connecticut State University and Juris Doctorate at Yale University School of Law. William V. La Via, M.D., FAAP Medical Director, Medical Affairs, RSV Prevention Sanofi I completed pediatric residency training as well as pediatric infectious diseases fellowship training at the University of California, Irvine medical center and the affiliated Miller Children's Hospital in Long Beach, CA. After training I spent 14 years in practice mostly in academic infectious diseases but 3 years were spent in private practice. In 2005 I moved to Medical affairs at MedImmune, which became a specialty division of AstraZeneca after its acquisition. I supported their infectious disease biologic portfolio, vaccines and respiratory biologics. During the pandemic, I transitioned to work at Karius, a pioneer in the detection of microbial cell-free DNA (mcfDNA) for serious, deep-seated infections, as a medical director in Medical Affairs. I have been interested in RSV since first conducting a clinical study during residency and am passionate about finding a solution to mitigate the impact on infants and young children each winter season. This led me to Sanofi where I joined Medical Affairs to work as a medical director focused on RSV disease prevention in 2020.

Drs. Vamsi Velcheti, Taofeek Owonikoko, and Janakiraman Subramanian discuss their experiences navigating the cancer drug shortage in the United States, the impact on patients and clinical trial enrollment, lessons learned, and proactive strategies to mitigate future crises. TRANSCRIPT  Dr. Vamsi Velcheti: Hello, I'm Dr. Vamsi Velcheti, your guest host for the ASCO Daily News Podcast today. I'm a professor of medicine and director of thoracic oncology at the Perlmutter Cancer Center at NYU Langone. On today's episode, we'll be discussing the impact of the shortage of cancer chemotherapy drugs across the United States. This has been affecting several thousands of patients with adult and pediatric cancers and hampering enrollment in clinical trials. Among the shortages are very commonly used drugs like cisplatin, carboplatin, methotrexate, and fludarabine. Some of these shortages have persisted since the time of the pandemic in 2020.   So today, to discuss this really troubling scenario, I have two outstanding colleagues, Dr. Janakiraman Subramanian, the director of thoracic oncology at Inova Schar Cancer Institute in Virginia, and Dr. Taofeek Owonikoko, a professor of medicine and the chief of the Division of Hematology and Oncology at the University of Pittsburgh Hillman Cancer Center in Pittsburgh.   Our full disclosures are available in the transcript of this episode, and disclosures relating to all episodes of the podcast are available at asco.org/DNpod.  So, a recent survey by the NCCN found that 90% of the nation's largest cancer centers have experienced a shortage in carboplatin, and 70% of the centers have reported a shortage in cisplatin. These are platinum-based chemotherapies we use frequently in patients with cancer, and these are often curative intent treatments for several cancers, and these are used in several tumor types, both solid tumors and hematologic malignancies. So, the scale of the problem is immense.   Dr. Owonikoko, I'd like to hear your take on this situation and how are you dealing with this at the UPMC Cancer Center.  Dr. Taofeek Owonikoko: Yeah, thank you, Dr. Velcheti, and happy to be part of this panel. As you rightly surmised, the chemotherapy drug shortage is what we've all experienced across the length and breadth of the United States. Our cancer center here in Pittsburgh is not an exception. We've had to be proactive as well as think outside the box to be able to manage the challenge. Just like every other cancer center across the country, maybe to varying degrees, we've had to look at patients in need of chemotherapy with these standard-of-care agents such as cisplatin or carboplatin, and to some degree docetaxel, during this past episode of drug shortage that we all went through. And while we did not have to, fortunately, cancel any patient treatment, we all went through it with bated breath; not sure of where the next batch of chemotherapy drugs will come through, but I would say in the past couple of weeks, we've actually seen some improvement in drug availability.   But before then, we've had to have contingency plans where, on a weekly basis, we review our patient list and the drug regimens that they're going to need, and must make sure that we have enough drug on hand for those patients. And in situations where we thought we might not have enough drug; we also had a plan to use alternative regimens. We were proactive in having guiding principles that are consistent with ASCO's recommendations in terms of quality care delivery for cancer patients. So, I'm sure that this is more or less the same approach adopted by other leading cancer centers across the country.   Dr. Vamsi Velcheti: Thank you, Dr. Owonikoko. And Dr. Subramanian, you're in a community setting, a large cancer center that serves a lot of patients in the state of Virginia. So, what is the scale of the problem at your institution and how are you handling it?   Dr. Janakiraman Subramanian: First of all, Dr. Velcheti, thanks for having me here on this panel. And as you rightly said, this is a significant problem, and it is across the country like Dr. Owonikoko said. And as medical oncologists, we are not always thinking of drug shortages. Our focus is on taking care of our patients. So, this is one more issue that we need to keep in mind now as we manage our patients with cancer. When this shortage started, the biggest problem, as you know, was when we became aware of this was primarily in cisplatin and we had some of our patients who were getting curative treatment and we had to make a decision - can they get cisplatin or can they get carboplatin. And one of the things we did was to have an ethics committee that will review each patient that is being planned to receive cisplatin-based chemotherapy and come to a decision on how best we can support them.   The template for some of this was based upon some of the triage mechanisms we used during COVID, as well as the ASCO guideline document for managing this chemotherapy shortage, which was one of the blueprints we used. And they have reviewed all cases, all patients that are being planned for cisplatin or carboplatin for that matter, and we come to a decision based on that. And we also have another committee that constantly monitors drug availability on a weekly basis and tries to forecast where the next problem would be as we take care of our patients.   And particularly as a lung cancer doctor, we've had situations where we had to use carboplatin instead of cisplatin and even we also have carboplatin shortage. And so, the committee usually approves two cycles at a time, but thankfully so far we have not had a situation where we could not offer our patients the chemotherapy treatment. But we are very carefully monitoring the situation, hoping that this will improve.   The other aspect of the shortage has been in 5FU. A lot of our GI colleagues; I treat esophageal cancer patients as well, where we've had to forego the bolus 5FU and have a 10% reduction on all 5FU infusions. And we've been using some of that dose reduction to ensure that we can have 5FU available for all our patients. And that's how we've been trying to manage this shortage situation here at Inova Schar.   Dr. Vamsi Velcheti: Dr. Subramanian and Dr. Owonikoko, we are oncologists, we are treating patients, and the toughest part really is telling a patient that we don't have access to certain drugs and we have to switch treatments to perhaps another treatment regimen that may be suboptimal. And it's always a very anxiety-provoking discussion, and especially for patients with metastatic cancer, they're already under a lot of stress and it's a really difficult conversation. How do you handle that, Dr. Owonikoko?  Dr. Taofeek Owonikoko: That's a conversation we all hope we don't have to have. And fortunately, with this current crisis, I've actually not had such misfortune of having to inform a patient that we don't have drugs to treat them or that we have to switch to something inferior. But conceptually, it's possible that could have happened and that would have been very difficult. But the one thing that we did, though, as part of our mitigation strategy was actually to inform the patient ahead of time because the way we handled this was to look at our inventory on a week-by-week basis. And if there are patients where we felt maybe they will be coming in towards the end of the week and we may not have enough drugs for them, to let them know the possibility exists that we might have to switch them to something different. While we did not have to do that for any patient, yes, there are patients that we had to give that heads up to, to say, “We're having this shortage. We're doing everything we can to make sure it's available. But just in case it's not available…” I think what is most important for most patients is to be aware of that decision ahead of time, to be able to process it, and to be transparent.   The other challenge that we face was, if you have to choose between patients, what should be your guiding principles as to who gets the drug and who doesn't get it? I think it's very easy for all of us to say, “Oh, if it's curative intent, we do it. If it's not curative intent, we don't do it.” It's a little more complicated than that because if we put the equity hat on, curative intent doesn't actually mean that that life is more valuable than somebody who cannot be cured. And this is where really, I think having people with expertise in ethics of care delivery and disaster management will be very important for us to proactively anticipate that, should this become a recurrent problem in the future that we actually have a well-vetted approach, just like we did during COVID where you have to ration resources that we have those people with expertise to help us as oncologists because not all of us, at least personally I can speak for myself, that is not my area of expertise and comfort.  Dr. Vamsi Velcheti: Excellent points. Dr. Subramanian, anything to add?  Dr. Janakiraman Subramanian: Oh, absolutely. I echo what Dr. Owonikoko said. These are conversations that we would like to hopefully never have with our patients. But this is a crisis that we are facing now. And personally, I can tell you two situations where we ran into this problem. But overall, though, we never had to stop a treatment or cancel a treatment for our patient. In the first situation, we had a young man with a rare germ cell tumor in the hospital for whom cisplatin was key. He was already in the ICU and sometimes the treatment start dates are not perfect, unlike what we do in the outpatient setting, depending on how well he's doing or the treatment start dates might move by a day or so. So we basically had to hold a certain dose of cisplatin for him.   This brings the next question, which is how do we decide who gets cisplatin versus who can go for an alternative option? And I think Dr. Owonikoko made a great point where, just because it is a curative disease does not mean their life is more valuable. This is where I think trying to make that decision at an individual level, as an individual treating physician can be extremely hard. And that's why at our institution we have this ethics committee where we have oncologists, pharmacists, and ethicists that review these chemotherapy orders, particularly for cisplatin, and try to use some guiding principles that we learned from COVID as well as ASCO's guidance to decide how we assign our resources. That's one option, one way we have done it.    And then in another situation that was faced by one of my GI oncology colleagues was a patient that was originally planned to go on a clinical trial where the chemotherapy backbone was FOLFOX and because we had the 5FU shortage, we could not offer that patient clinical trial enrollment. And that was a tough conversation where they had to tell them that they could not go on a clinical trial that they were looking forward to. And this then brings the next question, which is by foregoing the bolus 5FU and by the 10% reduction in the infusional 5FU, are we providing them inferior treatment? And it's a conversation that's had at a very individual level. I don't envy my colleague who had to have that conversation. It's a challenge and we try to do our best to communicate to our patients that we are trying to provide care without trying to compromise the effectiveness of treatment for them.  Dr. Vamsi Velcheti: Thank you so much both of you. And we had the same issues here at NYU in New York City as well. It appears, you know, the degree of shortage and the drugs that are in shortage has been somewhat different at different locations across the United States. But the theme has been that we are having to ration treatments for our patients. And of course, there are some tumor types where there's really no adequate substitution, for example, GU cancers. I mean, you can't really not give them cisplatin. A lot of these are situations which have curative intent and young patients. So, it's really troubling.   And I think one of the things that really came out of this is there's been a lot of push from professional societies that actually ASCO has been spearheading and some intense discussions with CMS and legislators to kind of provide more long-term fix for these things. And I think all of us have to be more engaged in those discussions with our professional societies like ASCO to kind of help promote awareness. So if you kind of think about it, these drugs are not that expensive. These are generic drugs that we've all been using for such a long time. And the fact that we can't provide these drugs for various reasons is kind of really concerning. We spend so much money on research and more expensive drugs and not being able to manufacture these drugs within the country and kind of having to rely on complex supply chains is troubling, and I hope the situation improves very soon.    So, I know both of you are at large cancer centers that enroll patients on clinical trials. Of course, these drugs, especially carboplatin, for lung cancer, especially, are like core treatments that are used in managing cancer patients with lung cancer. So how is this affecting your clinical trial accrual? Are you prioritizing patients on clinical trials for these drugs? Have you had to make any decisions to hold clinical trial accrual for certain trials? Kind of curious to hear.  Dr. Taofeek Owonikoko: Yeah, so I can maybe weigh in a little bit on that in terms of what we've had to do for patients receiving treatment as standard of care versus those going on clinical trials. As we all recognize that when a patient goes on a clinical trial, even if they are going to receive a standard-of-care regimen as part of that trial, it still has to be administered in line with the protocol. So, during the extreme period of shortage anxiety, we actually had consideration for perhaps not putting patients on trial if we're not sure that they will be able to continue to receive the protocol-mandated treatment, whether it's a control intervention or the experimental intervention.   The good thing to come out of this is at least here at UPMC, we actually did not have any instance where we had to deny a patient clinical trial participation. But there were anxious periods when we already had patients enrolled and they were scheduled to receive a platinum-containing regimen and we were not sure whether or not we were going to have adequate supply of the drug for them while on trial. I think this really raises an important consideration going forward as we come out of this current shortage. I don't by any stretch of the imagination assume that this is going to be the last one we experience, but I think the lessons learned here, we have to also carry that forward both in the design of the trial as well as in the regulatory environment surrounding clinical trial conduct, to say, should another incidence of drug shortage are to happen, how do we actually operationalize that with respect to patients on trial, whether starting or already on trial?   I think it's much more challenging when the patient is already on the trial, they've already started. It's less challenging if you just have to make a decision about somebody starting newly on the trial. But equally important is that by not allowing new patients to go on trial is denying something that potentially could be of benefit to them, albeit it is still a trial, it's not an established treatment option yet.  Dr. Janakiraman Subramanian : I completely agree with Dr. Owonikoko. Those were very key points and issues that we face as well. In terms of my patients with lung cancer, we haven't had a problem in getting them on clinical trials. Even though we have had carboplatin shortage patients who are already on treatment, they were able to get the carboplatin. For new patients, we were still able to provide them carboplatin as well. The biggest problem for clinical trials has been primarily with my GI colleagues who have to use 5FU. And there, as I said before, we are unable to give bolus 5FU and there is a 10% reduction of the infusional 5FU. So, we can't have any of these patients go on clinical trials.    And as a result, anything that has to do with 5FU has come to a screeching halt in terms of clinical trials for our patients. And I think I echo the point of Dr. Owonikoko that by no means this is the last drug shortage we're going to be dealing with and we are here today discussing this, also because this shortage has not ended. It's been ongoing. It's one of the longest drug shortages in my memory as a medical oncologist, and that's concerning. We still see that there is some improvement, but we haven't gotten past it yet.     And therefore, as we develop clinical trials and we need to have methods to address drug shortages and how we manage patient enrollment as well as how do we manage existing patients who are already on a clinical trial and, if possible, what might be their options in that situation. We may not have all the answers, but it is definitely an issue that we need to think about in the future as we develop and implement newer clinical trials for our patients.  Dr. Vamsi Velcheti: I completely agree and great points, both of you. And we've had the same issues with clinical trials at NYU Langone as well due to the shortage. It's been a challenge, and I think this is a problem that's so complex because of supply chain issues and the way the drugs are priced and incentives for manufacturing these drugs in the United States are not lucrative enough to actually onshore a lot of the production of these drugs.   I think at the end of the day, I think we have to come up with some creative, innovative, reimbursement structures for these generic chemotherapy drugs. I think this would require a very complex economic solution that perhaps ASCO and other organizations should kind of really foster an environment of innovation to kind of help facilitate onshoring some of the manufacturing of these key drugs within the United States. I think ASCO is already trying to do that, trying to collaborate with all the stakeholders to kind of address this problem is very critical, and I think all of us have to be engaged in some of the advocacy efforts that are ongoing to kind of address these drug shortages. And this is not a short-term problem.  So, Dr. Owonikoko and Dr. Subramanian, any final thoughts before we wrap up the podcast today?  Dr. Janakiraman Subramanian: So, Vamsi, you mentioned the whole complex supply chain and the fact that we rely primarily on overseas manufacturers to get these drugs that are off-patent but still a key backbone of our cancer treatment. I think those are all key issues that policymakers and leaders in the field have to keep in mind. As an institution at Inova, one of the key mechanisms that have helped us to sort of stay ahead of the shortage was to have this inventory management team that monitors the inventory out there. And in fact, the inventory management team does have access to what the inventory is in some of their main suppliers in terms of the drugs. And they also have an idea of how many patients are going through treatment, what is the weekly usage of a specific drug like carboplatin. And they try to forecast what is coming down the road and try to prepare for it.   And as we try to look for solutions, maybe a forecasting mechanism in a larger scale like either spearheaded by ASCO or by policymakers level that can, for the overall country, try to see where some of the inventory is for some of these critical drugs and try to prepare for it ahead of time, rather than wait till we hit the shortage and then try to find alternative suppliers to get the drug, which obviously doesn't happen quick enough. It takes months or even longer to catch up and get the inventory back to the level where we can comfortably take care of our patients.  I think that is something we should be advocating for that as well as the professional societies should take a handle on that and see if they can support something like that as well as letting the institutions know ahead of time what's coming might be very helpful.  Dr. Vamsi Velcheti: Yeah, very good point, Janakiraman, and I think that's a key takeaway here. I think we have to learn from other industries and try to– I mean this is not unique to healthcare by any means. I mean these chronic shortages due to supply chain issues, inventory management, there might be some learnings from other industries here that we probably should also focus on inventory management and improve supply chain logistics.   Dr. Owonikoko, any closing thoughts?   Dr. Taofeek Owonikoko: Yeah, I agree as well with all the points made by Dr. Subramanian and yourself. This is a chronic problem that requires a long-term strategy. I think it's both an economic problem as well as a regulatory problem. As we all know, part of the reason why we went through this current crisis is the regulatory decision by the FDA regarding safety of one of the manufacturers. So being proactive in terms of how these audits are conducted and giving people lead time I think will help avoid similar situations in the future.    It's an economic problem. There's a reason why a lot of the big pharma companies are not producing these drugs. And if the cost of production is such that the amount of money you get paid is enough to cover your price, I think there is an economic issue there to be addressed. That is unfortunately not within the scope of what any one of us can do individually, but as advocates in terms of the structure of incentivizing new drug versus old drug, some of these newer drugs are quite expensive, but oftentimes they are used along with standard drugs that are not as expensive. So, where do we strike that balance where we do not stifle innovation but at the same time, we don't create a perverse incentive system where everybody just wants to come up with the newest, most expensive drug and nobody is interested in really producing the backbone chemotherapy and other agents that will make those new drugs work well.   So, I think we have to pay attention. We have to advocate for our patients through our different institutions and organizations, and I hope that society as a whole that we've learned a lot of lessons from this crisis and that will help us craft some long-term strategies.   Dr. Vamsi Velcheti: Thank you both Dr. Owonikoko and Dr. Subramanian for your time today to speak with me and our listeners and for sharing your insights with us on the ASCO Daily News podcast.   Dr. Taofeek Owonikoko: Thank you.   Dr. Janakiraman Subramanian: Thank you.  Dr. Vamsi Velcheti: And thank you to our listeners for your time today. 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 podcast. Thank you so much.  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.  ASCO Resources Related to Drug Shortages are available here.     Follow today's speakers:    Dr. Vamsidhar Velcheti    @VamsiVelcheti    Dr. Janakiraman Subramanian  @RamSubraMD  Dr. Taofeek Owonikoko  @teekayowo    Follow ASCO on social media:     @ASCO on X (formerly Twitter)    ASCO on Facebook    ASCO on LinkedIn      Disclosures:     Dr. Vamsidhar Velcheti:     Honoraria: ITeos Therapeutics    Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen, Elevation Oncology, Taiho Oncology, Merus    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. Janakiraman Subramanian:  Consulting or Advisory Role: AstraZeneca, Boehringer Ingelheim, Pfizer, Novartis, Daichi, G1 Therapeutics, Jazz Pharmaceuticals, Janssen Oncology, Lilly, Blueprint Medicines, Axcess, BeiGene, Cardinal Health, Takeda, OncoCyte  Speakers' Bureau: AstraZeneca, Boehringer Ingelheim, G1 Therapeutics, Jazz Pharmaceuticals, Janssen Oncology  Research Funding (Inst.): G1 Therapeutics, Tesaro/GSK, Novartis, Genentech, Novocure, Merck   Dr. Taofeek Owonikoko:  Stocks and Other Ownership Interests: Cambium Oncology, GenCart, Coherus Biosciences  Consulting or Advisory Role: Novartis, Celgene, Abbvie, Eisai, GI Therapeutics, Takeda, Bristol-Myers Squibb, MedImmune, BerGenBio, Lilly, Amgen, AstraZeneca, PharmaMar, Boehringer Ingelheim, EMD Serono, Xcovery, Bayer, Merck, Jazz Pharmaceuticals, Zentalis, Wells Fargo, Ipsen, Roche/Genentech, Janssen, Exelixis, BeiGene, Triptych Health Partners, Daichi, Coherus Biosciences  Speakers Bureau: Abbvie  Research Funding (Inst.): Novartis, Astellas Pharma, Bayer, Regeneron, AstraZenece/MedImmune, Abbvie, G1Therapeutics, Bristol-Myers Squibb, United Therapeutics, Amgen, Loxo/Lilly, Fujifilm, Pfizer, Aeglea Biotherapeutics, Incyte, Merck, Oncorus, Ispen, GlaxoSmithKline, Calithera Biosciences, Eisai, WindMIL, Turning Point Therapeutics, Roche/Genentech, Mersana, Meryx, Boehringer Ingelheim  Patents, Royalties, Other Intellectual Property (Inst.):   Overcoming Acquired Resistance to Chemotherapy Treatments Through Suppression of STAT3  Selective Chemotherapy Treatments and Diagnostic Methods Related Thereto  DR4 Modulation and Its Implications in EGFR-Target Cancer Therapy Ref: 18089 PROV (CSP) United States Patent Application No. 62/670,210 June 26, 2018 (Co-Inventor)  Soluble FAS ligand as a biomarker of recurrence in thyroid cancer; provisional patent 61/727,519 (Inventor)  Other Relationship: Roche/Genentech, EMD Serono, Novartis  Uncompensated Relationships: Reflexion Medical           

Sharon L. Tasman is a seasoned business and technology attorney with over 30 years of legal experience. Having spent 15 years at Hogan Lovells, one of the world's largest law firms, and serving as in-house counsel at MedImmune, Sharon founded HTBiz Law to offer clients the best of both worlds—a boutique law firm experience with the expertise of a global firm. She has successfully negotiated complex contracts and managed individual transactions exceeding $200 million, while also providing comprehensive training and authoring publications on legal matters. Sharon's passion lies in empowering women and members of the BIPOC community to start and grow their businesses. With her unique blend of legal expertise, technical knowledge, and firsthand entrepreneurial experience, she understands the challenges faced by solo and small businesses and offers tailored solutions to overcome them. Sharon holds a Juris Doctor degree with honors from the University of Maryland School of Law and is admitted to practice law in multiple states. As a trusted advisor, Sharon assists companies of all sizes - from solo business owners to multi- national corporations - in protecting and expanding their ventures. Having worked on deals totaling over $6 billion, she understands the importance of addressing legal details as early in the process as possible. Sharon's mission is to provide accessible, non-threatening, legal resources that empower businesses to safeguard their interests and thrive in the competitive landscape. Sign up for a free consult at: https://calendly.com/htbizlaw/consultation Download my free e-book "Legal Essentials Roadmap - 6 Must-Haves to Protect and Grow Your Services Business" at https://roadmap.htbizlaw.com https://www.youtube.com/@htbi https://www.instagram.com/htbizlaw/

Drs. Douglas Flora and Shaalan Beg discuss the use of artificial intelligence in oncology, its potential to revolutionize cancer care, from early detection to precision medicine, and its limitations in some aspects of care. 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 the vice president of oncology at Science37 and an adjunct associate professor at the UT Southwestern Medical Center in Dallas.   On today's episode, we'll be discussing the use of artificial intelligence in oncology, its potential to revolutionize cancer care from early detection to precision medicine, and we'll also go over limitations in some aspects of care. I'm joined by Dr. Douglas Flora, the executive medical director of oncology services at St. Elizabeth Healthcare in northern Kentucky, and the founding editor-in-chief of AI in Precision Oncology, the first peer-reviewed, academic medical journal dedicated specifically to advancing the applications of AI in oncology. The journal will launch early next year.   You'll find our full disclosures in the transcript of this episode and disclosures of all guests on the podcast are available at asco.org/DNpod. Doug, it's great to have you on the podcast today.  Dr. Douglas Flora: I'm glad to be here. Thanks for having me.  Dr. Shaalan Beg: First of all, Doug, congrats on the upcoming launch of the journal. There has been a lot of excitement on the role of AI in oncology and medicine, and also some concern over ethical implications of some of these applications. So, it's great to have you here to address some of these issues. Can you talk about how you got into this space and what motivated you to pursue this endeavor?  Dr. Douglas Flora: I think, Shaalan, I've embraced my inner nerd.  I think that's pretty obvious. This is right along brand for me, along with my love of tech. And so, I started reading about this maybe 5, 6, 7 years ago, and I was struck by how little I understood and how much was going on in our field, and then really accelerated when I read a book that the brilliant Eric Topol wrote in 2019. I don't know if you've seen it, but everything he writes is brilliant. This was called Deep Medicine, and it touched on how we might embrace these new technologies as they're rapidly accelerating to ultimately make our care more human. And that really resonated with me. You know, I've been in clinical practice for almost 20 years now, and the same treadmill many medical oncologists are on as we run from room to room to room and wish we had more time to spend in the depths of the caves with our patients. And this technology has maybe lit me up again in my now 50-year-old age, say, wow, wouldn't it be great if we could use this stuff to provide softer, better, smarter care?  Dr. Shaalan Beg: When I think about different applications in oncology specifically, my mind goes to precision oncology. There are many challenges in the precision oncology space from the discovery of new targets, from finding people to enroll them on clinical trials, ensuring the right person is started on the right treatment at the right time. And we've been talking a lot about and we've been reading and hearing a lot about how artificial intelligence can affect various aspects of the entire spectrum of precision medicine. And I was hoping that you can help our listeners identify which one of those efforts you find are closest to impacting the care that we deliver for our patients come Monday morning in our clinics and which have the highest clinical impact in terms of maturity.  Dr. Douglas Flora: You know, I think the things that are here today, presently, the products that exist, the industry partners that have validated their instruments, it's in 2 things. One is certainly image recognition, right? Pattern doctors like dermatologists and people that read eye grounds and radiologists are seeing increasing levels of accuracy that now are starting to eclipse even specialists in chest radiology and CT or digital pathology with pixelated images now for companies like Path AI and others are publishing peer review data that suggests that the accuracy can be higher than that of a board-certified pathologist. We're all seeing stuff in USA Today and the New York Times about passing medical boards and passing the bar. I think image recognition is actually right here right now. So that's number 1.   Number 2, I think is less sexy, but more important. And that is getting rid of all the rote mechanical mundane tasks that pollute your days as a doc. And I mean specifically time spent on keyboard, pajama time, documenting the vast amounts of material we need for payers and for medical documentation. That can be corrected in hours with the right programming. And so, I think as these large language models start to make their way into clinic, we're going to give doctors back 3, 4, 6 hours a day that they currently spend documenting their care and let them pay attention to their patients again, face to face, eye to eye.  Dr. Shaalan Beg: I love the concept of pajama time. It's sort of become normalized in many folks that the time to do your charting is when you're at home and with your family or in your bedroom in your pajamas, cleaning notes and that's not normal behavior. But it has been normalized in clinical care for many reasons, some necessary and just some not maybe so much. We hear about some of the applications that are coming into electronic medical records. It's been many years since I saw this one demo which one of the vendors had placed where the doctor talks to the patient and then asks the electronic medical record to sum up the visit in a note and then voila, you have a note and you have the orders and you have the billing all tied up. It's been at least 4 years since I've seen that. And I'm not seeing the applications in the clinic or maybe something's turning around the corner because for a lot of people, AI and machine learning was just an idea. It was pie in the sky until chat GPT dropped and everybody got to put their hands on it and see what it can produce. And that's literally scratching the surface of what's possible. So, when you think about giving the doctors their pajama time back, and you think about decision support, trial matching, documentation, which one of those applications are you most excited about as an oncologist?  Dr. Douglas Flora: I'm still in the trenches.  I just finished my Wednesday clinic notes Friday afternoon at 4:30 pm, so I think medical documentation is such a burden and it's so tedious and so unnecessary to redouble the efforts again and again to copy a note that four other doctors have already written on rounds It's silly. So, I think that's going to be one of the early salvos that Hospital systems recognize because there's a higher ROI if you can give 400 doctors back two hours a day. It's also satisfying because the notes will be better. The notes will be carefully curated. They may bring in order sets for the MRI with gadolinium that you forgot you wanted to order; the digital personal assistant will get that. It will set a reminder on your calendar to call the patient back with their test results. It will order the next set of labs, and you're going in the next room, and you're going to be watching that patient in the room. And I've talked to other colleagues about this earlier today. You'll be able to see the daughter getting hives because you're watching her or the look that fleets across the husband's face when you go a little bit too far and you go out too much information when they're not quite ready for that. And I think that's the art of oncology that we're missing when we're flying in a room, and we've got our face on the screen and a keyboard, and we're buried in our own task and we're not there to be present for our patients. So, I'm hopeful that that's going be one of the easy and early wins for oncologists.  Dr. Shaalan Beg: Fantastic. And when we think about the spectrum of cancer care for the people who we care for, a lot happens before they walk into their medical oncologist's office in terms of early identification of cancer, just the diagnosis of cancer, the challenges around tissue acquisition, imaging acquisition. You mentioned a couple of the tools around radiomics, which are being implemented right now. Again, same question: Separate fact from fiction, which ones are we going to see in 2023 or 2024 in the clinical practice that we have? We've been hearing that pathologists and radiologists are going to be out of their jobs if AI takes off, right? Of course, that is a lot of hyperbole there. But how do you view that space and how do you see it impacting the overall burden of care that people receive, and the burden of care that physicians are experiencing?  Dr. Douglas Flora: I'm an eternal optimist, almost infuriating optimist to my partners and colleagues. So, I'm going to lean into this and say, burdens are going be reduced all over the place. We're going to have personal digital navigators to help our patients from the first touch so that they're going to have honest and empathetic questions answered within an hour of diagnosis. The information that they're going have at their fingertips with Chatbot 4 or Med-PALM 2 with Google that's about to be released as a medical generative AI. These are going to give sensitive and empathetic answers that don't put our patients on the cliff, you know, that they're falling off waiting for a doctor's visit 10 days down the road. So, I think the emotional burdens will be improved with better access to better information. I think that the physicians will also have access to that, giving us reassurance that we're going down the right path in terms of really complicated patients taking very, very large datasets and saying a digital twin of this patient would have been more successful with this approach and those sorts of things. And those are probably 3 to 5 years down the road but being tested heavily right now in academic settings with good data coming.  Dr. Shaalan Beg: Robotic empathy sounds like an oxymoron.    Dr. Douglas Flora: Yeah, look at the published studies.   Dr. Shaalan Beg: We've all seen the data on how a chatbot can outperform physicians in terms of empathy. I really find that to be hard to stomach. Help me out.  Dr. Douglas Flora: Yeah, we say that, and we say that to be provocative, but no, there's no substitute for a clinician laying a hand on a patient. We talked about how you need to see that fleeting glance or the hives on the daughter's chest and that you've gone too far and shared too much too soon before that family is ready for it. I have no doubt in my mind, these tools can make us more efficient at our care, but don't get me wrong. There's no chance that these will replace us in the room, giving a hug to a patient or a scared daughter. They're going to remember every word you say; I just want it to be the right words delivered carefully and I don't want us to rush it. So ultimately, as we make our care more human, these tools might actually give us time back in the room to repair that doctor-patient relationship that's been so transactional for the last 4 or 5 or 10 years. And my hope is, we're going to go back to doing what we went into oncology to do, to care deeply about the patients in our care and let the computers handle the rote mechanical stuff; let me be the doctor again and deserve that patient's attention and give it right back in return.   Dr. Shaalan Beg: And I think we're hearing a lot of themes in terms of AI helping the existing clinical enterprise and helping make that better. And it's not your deep blue versus Kasparov, one person is going to win. It's the co-pilot. It's reducing burden. It's making the work more meaningful so that the actual time that's spent with our patients is more meaningful and hopefully can help us make deeper connections.   Let's talk about challenges. What are some of the challenges that worry you? There've been many innovations that have come and gone, and health systems and hospitals have resisted change. And we all remember saying during COVID that we're never going to go back to the old ways. And here we are in 2023 and we are back to the old ways for a lot of things. So, what are the major limitations of AI, even at its... peak success that you see, which our listeners should be aware of, and which may worry you at times.  Dr. Douglas Flora: Well, you've actually spoken to why I started this journal. I want to make sure that clinicians are guiding some of those conversations to make sure that guardrails are up so that we're ethical and we are making sure that we are policing bias. It's no secret now you've seen these things – a lot of language models, a lot of the deep learning was programmed by people that look like me and did not include things that were culturally competent. You can look at data that's been published on Amazon and facial recognition software for Facebook and Instagram and others. And they can identify me out of a crowd as a middle-aged white guy, but 60% of the time they will not recognize Oprah Winfrey or Serena Williams or Michelle Obama. I mean, iconic global icons. And with darker skin, with darker features, with different facial features than my white Caucasian, Eurocentric features, these recognition softwares are not as good. And I'm worried about that for clinical trial selection and screening for that. I'm really, really worried about building databases that don't represent the patients in our charge. So bias is a big deal and that's got to be transparent. That's got to be published how you arrived at this decision. And so that would be number 1. Number 2 is probably that we don't have as much. visibility to how decisions are made, this so-called black box in AI. And that's vexing for doctors, especially conservative oncologists that need 3 published randomized phase 3, blinded, placebo-controlled trials before we move an inch. So, there must be more transparency. And that again is in publications, it's in peer review. They say we need real scientific rigor and not to belabor this, but our industry partners are well ahead of us. We're not generally inclined to believe them until we see it because I've got 150 AI companies coming to my hospital system as vendors some of them are worthy great partners and some of them are a little bit over their skis and selling more than they can actually deliver yet. So, I'd like to give that an opportunity to see the papers. There's about 300 produced a day in AI in medicine. Let's give them a forum and we'll duke it out with letters of the editor and careful review.  Dr. Shaalan Beg: I will say Doug, it is becoming hard to separate fact from fiction. There is so much information which is coming across us in medical journals and through our email, through our professional social media accounts that I sometimes worry that people will just start tuning it all out because they can't separate the high impact discoveries from the more pie in the sky ideas. So, tell us more about how we got here and how you see this curve of enthusiasm shifting maybe in the next 6 months or 1 year.  Dr. Douglas Flora: Yeah, it's a great question. And it's rapidly accelerating, isn't it? We can't escape this. It's entering our hourly lives, much like the iPhone did before, or me having to switch from my BlackBerry to a smartphone that didn't have buttons. I felt like I was adapting. And maybe this is what people felt like when Henry Ford was out there, and all the buggy drivers were getting fired. The reality is it's here and it was here 6 months ago. And maybe we're feeling that urgency and maybe it's starting to catch on in general society because the advent of generative AI is easier to understand. These aren't complicated mathematical models with stacking diagrams and high-tech stuff that's just happening in Palo Alto. It's Siri, it's Cortana. It's my Google digital assistant notifying me that it's time to get on for my next meeting. And those things have been infiltrating our daily lives and our minds quietly for some time. About November 30th when chatbot GPT-3 came out from OpenAI and we started toying with it, you started to see the power. It can be creative, it can be funny, it can articulate your thoughts better than you can articulate them on paper immediately. English students have figured it out. People in marketing and writing legal briefs have figured it out and it's coming to medicine now. It is actually here, and this might be one instance where I think the hype is legit. and these tools will probably reshape our lives.   There have been some estimates by Accenture that 70% of jobs in medicine are going to be altered irretrievably by generative AI. And so, I think it's incumbent upon those of us that are leaders in healthcare systems to at least assemble the team that can help make sense and separate, like you said, the signal from the noise. I know we're doing that here at St. Elizabeth Healthcare. We've got a whole team being formed around this. We have 5 or 6 different products we bought. that we're using to help read mammograms and read lung nodules and read urinalyses, etc. You need a construct to do that appropriately. You need a team of people that are well read and well-studied and able to separate that fact from fiction. I think we're all going to have to work towards that in the next 6 to 12 months.  Dr. Shaalan Beg: Tell me about that construct. How did you, what is the framework that you use to evaluate opportunities as they come through the door?  Dr. Douglas Flora: It's something I think we're all struggling with. As I mentioned, we've got all of these fantastic industry partners, but you can't buy 200 products off the shelf as Epic add-ons as third-party software to solve 200 problems. So, it's interesting, you've just said this. I just shared a piece on LinkedIn that I loved. “Don't pave the cow's path.” It's a really thoughtful thing to say, “Before you build an AI solution, let's make sure we're solving the correct problem.” And the author of that piece on Substack said: Let's not use AI to figure out how to have more efficient meetings by capturing our minutes and transcribing them immediately. Let's first assess how many of these meetings are absolutely necessary. What's the real job to be done and why would you have 50% of your leadership team in meetings all day long and capture those in yet another form? Let's take a look first at the structure around the meetings and say, are these necessary in 2023 and are these productive?   So, my thought would be as we're starting this. We're going to get other smart people who are well-read, who are studying, who are listening to experts that do it six months ahead of us, and really doing a careful contemplative look at this as a team before we dive in with both feet. And there are absolutely tools that are going to be useful, but I think the idea, how do we figure this out without having 200 members of my medical staff coming to me saying, you've got to purchase all 200 of these products, and have a way to vet them scientifically with the same rigor you would for a journal before you put out that kind of outsource.  Dr. Shaalan Beg: Doug, thanks for coming on the podcast today and sharing your valuable insights with us on the ASCO Daily News Podcast. We'll be looking out for your journal, AI in Precision Oncology, early next year. Tell our listeners where they can learn more about your journal.  Dr. Douglas Flora: I really appreciate you guys having me. I love this topic, obviously, I'm excited about it. So, this journal will be ready for a launch in early October in a preview. And then our premier issue will come out in January. We're about to invite manuscripts in mid-August. I guess parties that are interested right now go to Doug Flora's LinkedIn page because that's where I'm sharing most of this and I'll put links in there that will lead you to Liebert's site and our formal page and I think we can probably put it in the transcript here for interested parties.   Dr. Shaalan Beg: Wonderful. Thank you very much and thank you to our listeners for your time today. Finally, if you have any insights on if you value the insights a little. And thank you to our listeners for your time today. Finally, if you value the insights that you hear on the 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. Douglas Flora   St. Elizabeth Healthcare     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. Douglas Flora:  Honoraria: Flatiron Health   

Dr. Neeraj Agarwal and Dr. Jeanny Aragon-Ching discuss the CLEAR study in renal cell carcinoma, a new exploratory analysis combining the TheraP and VISION trials in metastatic urothelial cancer, and compelling advances in prostate cancer and across GU oncology in advance of the 2023 ASCO Annual Meeting.  TRANSCRIPT Dr. Neeraj Agarwal: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, your guest host for the ASCO Daily News Podcast today. I'm the director of the Genitourinary Oncology Program and a 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 Dr. Jeanny Aragon-Ching, a GU medical oncologist and the clinical director of the Genitourinary Cancers Program at the Inova Schar Cancer Institute in Virginia.   Today, we'll be discussing some key abstracts in GU oncology that will be featured at the 2023 ASCO Annual Meeting.  Our full disclosures are available in the show notes and disclosures of all guests on the podcast can be found on our transcript at asco.orgDNpod.   Jeanny, it's great to have you on the podcast today. Dr. Jeanny Aragon-Ching: Thank you so much, Dr. Agarwal, for having me. Dr. Neeraj Agarwal: Jeanny, let's begin with Abstract 4502 regarding long-term updated results on the CLEAR study. The abstract reports the final, prespecified overall survival analysis of the CLEAR trial, a four-year follow-up of lenvatinib plus pembrolizumab versus sunitinib in patients with advanced renal cell carcinoma. Dr. Jeanny Aragon-Ching: Yes, I would be happy to. So, just as a reminder, the combination of lenvatinib and pembrolizumab was initially approved by the FDA in August 2021 for first-line treatment of adult patients with advanced renal cell carcinoma. So, this was based on significant benefits that were seen in progression-free survival, which was a primary endpoint, but also showed improvement in the overall response rates compared with sunitinib in first-line advanced renal cell carcinoma.   So this abstract reports on longer-term follow-up now at a median of 49.8 months, and PFS favored the combination lenvatinib and pembrolizumab compared to sunitinib across all MSKCC risk groups, and PFS benefit versus lenvatinib and pembro compared to sunitinib was maintained with a hazard ratio of 0.47. And even overall survival was also maintained with the combination with a hazard ratio of 0.79, and the overall survival favored the combination across all risk groups. If we look at the CR rate, it was 18.3% for the combination compared to 4.8% with sunitinib, unless patients in the combination arm received subsequent anticancer therapies, and that's intuitive. And the PFS2 was also longer with the combination at 43 months compared to 26 months. Now, it is important to note that grade III or more treatment-related adverse events did occur in about 74% of the patients in the combination of lenvatinib and pembro, compared to 60.3% in patients with sunitinib. Dr. Neeraj Agarwal: Jeanny, this is good news. So the main message from the abstract is that sustained results from this combination of lenvatinib plus pembrolizumab are being seen even after a longer follow-up of more than four years.  Dr. Jeanny Aragon-Ching: Yes, I agree. So now, moving on, Neeraj, to a different setting in the RCC space, let's look at Abstract 4519, which is titled “Efficacy of First-line Immunotherapy-based Regimens in Patients with Sarcomatoid and/or Rhabdoid Metastatic Non-Clear Cell RCC: Results from the IMDC,” which will be discussed by Dr. Chris Labaki. So, Neeraj, based on this abstract, can you tell us a little bit more about the impact of these adverse pathologic risk features in non-clear cell RCC?  Dr. Neeraj Agarwal: Of course. So, using real-world patient data, the IMDC investigators compared the outcomes of patients with metastatic non-clear cell RCC who were treated with immunotherapy-based combination regimens versus those who were treated with VEGF-TKIs alone. They also assessed the impact of sarcomatoid and rhabdoid features on response to IO-based combinations versus VEGF-TKIs. Of 103 patients with metastatic non-clear cell RCC who had rhabdoid or sarcomatoid features, 32% of patients were treated with immunotherapy-based combinations.   After adjusting for confounding factors, the authors show that those treated with a combination of two immune checkpoint inhibitors or an immune checkpoint inhibitor with a VEGF-TKI combination had significantly improved overall survival, which was not reached in the immunotherapy combination group versus seven months within the VEGF-TKI group. Time to treatment failure and objective responses were also prolonged, significantly higher, and better in the immunotherapy groups compared with patients who were treated with VEGF-TKIs alone. Interestingly, if you look at those 430 patients with metastatic non-clear cell RCC who did not have sarcomatoid or rhabdoid features, they didn't seem to benefit with immunotherapy-based combinations.  Dr. Jeanny Aragon-Ching: This is an exciting update, Neeraj. What are the key takeaways from this abstract? Dr. Neeraj Agarwal: So the main takeaway is if you see a patient with advanced non-clear cell RCC who has sarcomatoid and rhabdoid features, there appears to be a rather substantial and selective benefit with IO-based combinations. And in this context, I would like to highlight the ongoing SWOG 2200 trial also known as PAPMET2 trial, which is comparing the combination of cabozantinib plus atezolizumab. So immuno-therapy-based combinations versus cabozantinib alone in advanced papillary renal cell carcinoma setting. So this trial is being led by Dr. Benjamin Maughan and Dr. Monty Pal. And I like to encourage our listeners to consider referring their patients for involvement in this federally funded trial so that we can validate the data from this retrospective study in a prospective way. So, Jeanny, let's now move on to another important disease type which is urothelial carcinoma. There is a very recent accelerated FDA approval of the drug combination of enfortumab vedotin and pembrolizumab for cisplatin-ineligible metastatic urothelial carcinoma patients. This is Abstract 4505, which is being presented by Dr. Shilpa Gupta and colleagues. Can you please tell us more about this update? Dr. Jeanny Aragon-Ching: Yeah, absolutely. So, as you mentioned, Neeraj, the FDA just granted accelerated approval in April 2023 for this combination of enfortumab vedotin or EV, which is and ADC, antibody drug conjugate against nectin-4 and the PD-1 inhibitor pembroluzimab. So it's a combination for patients with locally advanced or metastatic urothelial carcinoma who are considered cisplatin ineligible. So this is nearly a four-year follow-up.   So as a reminder, this was a phase 1b/2 trial that included 45 patients and it had a primary endpoint of safety and tolerability although the key secondary endpoints included confirmed overall responses, duration of response, progression-free survival, and the resist criteria was investigated via investigator and BICRs which is in a blinded independent central review. Even overall survival was a key secondary endpoint.  So, the bottom line was the confirmed overall response by BICR was 73.3%, the disease control rate was about 84%, and the CR rate was 15.6% with a PFS of close to 13 months, and a 12-month overall survival rate of 83%. However, it is important to cite that there were treatment-related adverse events including skin reactions in 66%, neuropathy occurred in 62%, and ocular disorders in 40%. And there was a little bit of pneumonitis in close to 9%, colitis, and hypothyroidism, so there are side effects to watch out for.  Dr. Neeraj Agarwal: So, Jeanny this is great. What is the key takeaway from this trial?  Dr. Jeanny Aragon-Ching: So I think the most important thing is we now have a new combination of EV and pembro which shows very promising responses and survival in part which led to the FDA accelerated approval in the cisplatin-ineligible population of patients. However, we must note that the phase 3 trial of EV302 will ultimately establish which approach is really beneficial for all of our cisplatin-ineligible patients, either a carboplatin-based chemotherapy regimen or a non-platinum-based regimen such as EV and pembro. Dr. Neeraj Agarwal: Thanks Jeanny, would you like to discuss any other study in the bladder cancer space? Dr. Jeanny Aragon-Ching: Absolutely. I think Abstract 4508 from Dr. Seth Lerner and colleagues will be very relevant to our colleagues. This abstract is SWOG S1011, which is a phase 3 surgical trial to evaluate the benefit of a standard versus an extended lymphadenectomy performed at the time of radical cystectomy for muscle-invasive bladder cancer.  Dr. Neeraj Agarwal: Yes. So this trial, as you said, is an important trial which randomized in a one-on-one fashion 618 patients with muscle-invasive bladder cancer undergoing radical cystectomy, and these patients were randomized to either standard lymph node dissection or an extended lymph node dissection. And standard lymph node dissection included, as we know, external and internal iliac and operative lymph node. The extended lymph node dissection included lymph nodes up to aortic bifurcation which included common iliac, presciatic, and presacral lymph nodes. At a median follow-up of approximately 6 years, there was no disease-free survival or overall survival benefit in patients undergoing an extended lymph node dissection compared to standard lymph node dissection. And extended lymph node dissection was also associated with greater morbidity and preoperative mortality. Dr. Jeanny Aragon-Ching: Very interesting data, Neeraj. So these results, I think, will be very useful for a lot of our surgical colleagues in both academia and the community who may still be inclined to perform extended lymphadenectomy during cystectomy. This study shows that it's actually not necessary. Dr. Neeraj Agarwal: Absolutely. So now let's move on to another disease type, which is very important - prostate cancer. There are several practice-informing abstracts that are worthwhile discussing. The first of these involves Abstract 5002, which looks at the impact of the PSA nadir as a prognostic factor after radiation therapy for localized prostate cancer, which will be presented by Dr. Praful Ravi and  colleagues. Jeannie, can you please tell us more about this abstract? Dr. Jeanny Aragon-Ching: Yeah, definitely. So this abstract, as you mentioned, Neeraj, is a prognostic impact of PSA nadir of more than or equal to 0.1 nanogram per ml within six months after completion of radiotherapy for localized prostate cancer - an individual patient data analysis of randomized trials from the ICECaP Collaborative. Basically, it refers to an attempt to evaluate early surrogate measures to predict for long term outcomes such as prostate cancer-specific survival, metastases-free survival, and overall survival. So they looked at a big registry from the ICECaP collaboration that included 10,415 patients across 16 randomized controlled trials. And those men underwent treatment for intermediate risk and high risk prostate cancer treated with either radiation therapy alone in about a quarter of patients, or they got RT with short-term ADT in about 58% of patients, and 17% of them got RT with long-term ADT.  So, after a median follow-up of ten years, what they found was, if you had a PSA nadir that is over or equal to 0.1 nanogram per ml within six months after completion of radiation therapy, it was associated with worse prostate cancer-specific survival, metastases-free survival, and overall survival. For instance, the five-year metastases-free survival for those who achieved a PSA nadir of less than 0.1 was 91% compared to those who did not, which was 79%. Therefore, they concluded that if you achieve a bad PSA of 0.1 or above within six months after you completed radiation, you had worse outcomes.  Dr. Neeraj Agarwal: Jeanny, what is the key takeaway message from this study? Dr. Jeanny Aragon-Ching: The key takeaway from this ICECaP analysis is that this information would be very important to augment a signal-seeking endpoint, especially for clinical trial development, so that we can develop further strategies to de-escalate for those who don't need systemic intensification or therapy intensification versus escalation for those who really do. Dr. Neeraj Agarwal: So, my radiation oncology colleagues need to watch out for those patients who do not achieve a PSA of less than 0.1 nanogram per ml within the first six months of finishing radiation therapy. Very interesting data.  Dr. Jeanny Aragon-Ching: Yes, absolutely. So. Neeraj another important abstract for our fellow clinicians, switching gears a little bit now, is Abstract 5011, which is titled “Do Bone Scans Overstage Disease Compared to PSMA PET?” This was an international, multicenter retrospective study with blinded, independent readers. Can you tell us more about this abstract? Dr. Neeraj Agarwal: Yes, a relatively small retrospective study, but still pertinent to our practice. So I'll summarize it. This study by Dr. Wolfgang Fendler and colleagues evaluated the ability of bone scans to detect osseous metastasis using PSMA PET scan as a reference standard. So in this multicenter retrospective study, 167 patients were included, of which 77 patients were at the initial staging of prostate cancer, 60 had biochemical recurrence after definitive therapy, and 30 patients had CRPC or castor-resistant disease.  These patients had been imaged with a bone scan and a PSMA PET scan within 100 days. And in all patients, the positive predictive value, negative predictive value and specificity for bone scan were evaluated at different time points. They had bone scan and PSMA PET scan and both were compared. And what they found was interesting. All these three values - positive predictive value, negative predictive value, and specificity for bone scan were 0.73, 0.82 and 0.82 in all patients, and in initial staging, it was even lower at 0.43 and 0.94 and 0.80.  So, without getting into too much detail regarding these numbers, I want to highlight the most important part of the study, that at the initial staging, 57% patients who had a positive bone scan had false positive bone scans. The interreader agreement for bone disease was actually moderate for bone scans and quite substantial for the PSMA PET scan.  Dr. Jeanny Aragon-Ching: So, Neeraj, what do you think is the key takeaway message here for our audience?   Dr. Neeraj Agarwal: The key takeaway message is that positive predictive value of bone scan was low in prostate cancer patients at initial staging, with the majority of positive bone scans being false positive. This suggests that a large proportion of patients which we consider to have low-volume metastatic disease by bone scan actually have localized disease. So in the newly diagnosed patients with prostate cancer, patients should ideally have a PSMA PET scan to rule out metastatic disease.   So, let's move on to another abstract I would like to discuss, which has important implications in treatment, especially now that lutetium 177 is approved, but frankly not available widely. Dr. Jeanny Aragon-Ching: Yeah, that's actually very timely. So the abstract you're referring to is 5045, which is being presented by Dr. Yu Yang Sun and colleagues entitled “Effects of Lutetium PSMA 617 on Overall Survival in TheraP Versus VISION Randomized Trials: An Exploratory Analysis.” So, Neeraj, can you tell us more about the relevance of this exploratory analysis? Dr. Neeraj Agarwal: Definitely. In this abstract, Dr. Yang Sun and colleagues assess the effect of lutetium PSMA on overall survival in two different trials, TheraP and VISION trials. So, just for our listeners' recollection, the phase 2 TheraP trial compared lutetium PSMA and cabazitaxel in patients with mCRPC who had progression on docetaxel and had significant PSMA avidity on gallium PSMA pet scan, which was defined as a minimum uptake of SUV max of 20 at least one site of disease and SUV max of more than 10 at all sites of measurable disease.  In this trial, 20 of 101 patients in the cabazitaxel arm crossed over to lutetium PSMA, and 32 of 99 patients in the lutetium PSMA arm crossed over to cabazitaxel. In the VISION trial, patients with mCRPC who previously progressed on at least one ARPI and one taxane-based therapy and had a positive gallium PSMA scan, and here, positivity was not stringently pre-specified as it was done in the context of TheraP trial. So, positive gallium pet scans were randomly assigned in two to one fashion to receive either lutetium PSMA plus best supportive care or standard of care versus standard of care.  And I'd like to highlight that the standard of care comprised ARPIs and bone protecting agents and these patients were not allowed to have cytotoxic chemotherapy such as cabazitaxel in the standard of care arm. Now, overall survival was similar in the lutetium PSMA group regardless of whether they got lutetium PSMA in the VISION trial or TheraP trial. There was no difference in overall survival with lutetium in the lutetium arms of VISION and TheraP trial with a hazard ratio of 0.92. And there was no difference in the overall survival between the lutetium PSMA and the cabazitaxel group in the TheraP trial if you use counterfactual analysis, assuming crossover had not occurred. So, quite interesting in my view. Dr. Jeanny Aragon-Ching: Yeah, thanks Neeraj for that wonderful synopsis and discussion. So, what is the key take home message then? Dr. Neeraj Agarwal: The main message in this new exploratory analysis, which combined both the TheraP and VISION trials, is that lutetium PSMA and cabazitaxel seem to be associated with similar overall survival benefit in these highly selected patients with PSMA positivity. Additionally, the difference in the observed effect of lutetium PSMA and overall survival in the TheraP and VISION trials may be actually better explained by the use of different treatments in the respective control arms of these trials. And these results, in my view, are quite pertinent for those patients and providers who do not have access to lutetium-177 therapy.  Let's go to another abstract that is currently relevant to our practice, given many patients with advanced prostate cancer who have concurrent diabetes; I'm talking about Abstract 5066. Jeanny, can you please tell us more about this abstract?  Dr. Jeanny Aragon-Ching: Certainly, Neeraj. So this abstract will be presented by Dr. Amy Shaver and colleagues. So it's also very relevant, since many men who are diagnosed with prostate cancer frequently also have a concomitant diagnosis of type 2 diabetes mellitus. So, this was a SEER-Medicare population database analysis that looked at men who were treated with either abiraterone or enzalutamide and also had concomitant diagnosis of type 2 diabetes mellitus (DM). And they were identified using ICD-9 and ICD-10 codes and they were all tied in to acute care utilization. So they looked at CMS research data codes and ER hospitalization visits six months after treatment initiation was recorded. So all in all, they took a sample of 11,163 men, of whom close to 62% were treated with abiraterone and about 38% were treated with enzalutamide.  So, of these, about 27% of them had type 2 DM, of whom 59% received abiraterone and about 41% had enzalutamide. So, the bottom line is, compared to those without diabetes mellitus, those who had type 2 diabetes had worse acute care utilization, which was 43% higher than those who got abiraterone compared to enzalutamide, and also had higher overall mortality. Therefore, the bottom line is, having type 2 diabetes mellitus, unfortunately, portends worse outcomes in men with prostate cancer, so careful attention needs to be paid to those who are starting out already with such comorbidities. So Neeraj, any final thoughts you have regarding this abstract and overall before we wrap up on the podcast today?  Dr. Neeraj Agarwal: Absolutely. So it looks like, based on this very important pertinent Abstract 5066, which talks about the impact of diabetes on our patients, I think we need to be very watchful regarding the impact of diabetes on our patients who are being treated with abiraterone or enzalutamide, especially drugs which are known to make the metabolic syndrome and diabetes worse. I think close monitoring and close attention to control of diabetes is very important. So with that, I would urge the listeners to come and join us at the Annual Meeting, not only to celebrate these successes but also to help disseminate this cutting-edge data to practitioners and maximize the benefit to our patients across the globe.   And thank you to our listeners for joining us today. You will find links to the abstracts we discussed today on the transcript of this episode. Finally, if you value the insights that you hear on our 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. Neeraj Agarwal @neerajaiims Dr. Jeanny Aragon-Ching Follow ASCO on social media:   @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn     Disclosures:  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. Jeanny Aragon-Ching: Honoraria: Bristol-Myers Squibb, EMD Serono, Astellas Scientific and Medical Affairs Inc., Pfizer/EMD Serono Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant,  Exelixis, Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb, Astellas/Seattle Genetics.