Podcasts about t dm1

Play Episode Listen Later May 21, 2024 76:27

Featuring perspectives from Dr Adam M Brufsky, including the following topics: Review of Local Therapy (0:00) Treatment Advances for HER2 Positive Early-Stage Breast Cancer (18:34) Case: A woman in her early 60s with ER-positive, HER2-positive (IHC 3+) with infiltrating ductal carcinoma who received T-DM1 with an aromatase inhibitor (19:37) Case: A woman in her early 50s with ER-positive, HER2-positive (IHC 3+) who received TCHP followed by a mastectomy (56:36) Beyond the Guidelines Survey and HERRISK (1:02:33) Trials in Progress (1:14:24) CME information and select publications

management er positive risk progress patients trials breast cancer oncology cme recurrence localized her2 ihc love understanding neil love t dm1 tchp

ADCs in Breast Cancer: Sequencing, Resistance, and Managing Toxicity

Play Episode Listen Later Feb 15, 2024 30:14

Drs. Hope Rugo and Sara Tolaney discuss the promise of antibody-drug conjugates (ADCs) in the treatment of breast cancer, highlighting key trials that shed light on matching the right ADC to the right patient in the right setting. They also explore how combinations and sequencing of ADCs can augment their efficacy, the mechanisms of resistance, and the future potential of biomarkers to predict patient response. TRANSCRIPT Dr. Hope Rugo: Hello, I'm Dr. Hope Rugo, your guest host of the ASCO Daily News Podcast today. I'm a professor of medicine and director of breast oncology and clinical trials education at the University of California, San Francisco's Comprehensive Cancer Center. Antibody-drug conjugates, or ADCs, are rapidly changing the treatment landscape for patients with breast cancer. ADCs consist of antibodies that target tumor-specific antigens on the cell surface, chemical linkers, and cytotoxic payloads that can act powerfully to kill cancer cells. On today's episode, we'll be discussing advances in research to match the right ADC to the right patients and in the right setting. We'll also talk about the next steps, assessing how combinations and sequencing of ADCs can augment their efficacy, improve options for patients, and identify biomarkers in the future to predict how patients will respond so that we can match the right treatment to the right patient and their tumor. We need to gain a better understanding of the mechanisms of resistance that occur upfront as well as under the pressure of treatment. Joining me for this important discussion is Dr. Sara Tolaney. Dr. Tolaney is an associate professor of medicine at Harvard Medical School, associate director of the Susan Smith Center for Women's Cancer, and chief of the Division of Breast Oncology at the Dana-Farber Cancer Institute in Boston. 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. Tolaney, we're delighted to have you on the podcast today. Thanks for being here. Dr. Sara Tolaney: Thank you so much for having me. I'm looking forward to the discussion. Dr. Hope Rugo: Great! So, we'll move forward, and because we're friends and colleagues, I'm going to refer to you as Sara, and I'm Hope, since we'll dispense with formalities in our discussion. A lot of the talks that we give about ADCs start out with “a revolution in breast cancer therapy.” And indeed, this is a really exciting time with ADCs as treatment for breast cancer, and we're rapidly moving these agents into earlier disease settings. Can you tell us a little bit about the possibilities and challenges of using ADCs for the treatment of breast cancer today? Dr. Sara Tolaney: It's interesting that you say antibody-drug conjugates as revolutionizing outcomes of breast cancer, which I think is true. But on the flip side, I think it's also bringing up a lot of questions about how to use them, when to use them, and how to manage side effects. So there are a lot of good strengths for these antibody-drug conjugates, but a lot of unknowns that we're still trying to figure out. We had an older antibody-drug conjugate T-DM1 that we were all very familiar with that for years had been a treatment that we used very commonly in metastatic disease and now even use in early breast cancer, and I think has changed outcomes for patients. But over time, we've been able to develop newer antibody-drug conjugates as the technology has really evolved so that these agents now are able to deliver a lot of chemotherapy into a cancer cell. We're seeing very high drug-to-antibody ratios, and we're also seeing that these drugs can function via bystander effect, whereas T-DM1, for example, was not able to do that. But our newer ADCs, like sacituzumab govitecan or trastuzumab deruxtecan, are agents that do allow chemotherapy to get into that cancer cell, but also to get into neighboring cells. And I think the technology evolution in being able to build these so-called next-generation ADCs has allowed for really unprecedented efficacy that we've not seen before. And it's also allowed us to develop these drugs in a way that's been different. Originally, we were developing T-DM1 to turn off HER2 signaling and to deliver chemotherapy into a HER2 cell. At least that's what we thought originally. And now we're really evolving so that we can just find a tiny bit of protein on a cancer cell and use it as a target, really in a subtype-agnostic way. And I think it's just a different way of thinking about how to use these agents to really deliver a lot of chemotherapy into cancer cells and have very robust efficacy. Dr. Hope Rugo: Yes, it is fascinating that some of the suppositions that we made with the first ADC don't seem to really hold true as well. And maybe they hold true in varying levels for the different ADCs. For example, this bystander effect is thought to allow us to target cells that have very low expression of the receptor that can be internalized even lower than our ability to detect these receptors by immunohistochemistry. And maybe we'll talk about that in a little bit. But first, you mentioned already sacituzumab and trastuzumab deruxtecan, the ADCs that are currently approved for breast cancer. But can you tell us a little more about those ADCs and the key trials that have led to approval of these targeted agents? Dr. Sara Tolaney: Yes, I think when we first saw the data that came out with T-DXd and DESTINY-Breast01, I think my jaw dropped because I had never seen a waterfall plot like that. This was a single-arm study that looked at T-DXd in patients with very heavily pretreated metastatic HER2-positive breast cancer and saw very high response rates of over 60% and a clinical benefit rate of almost 98%, meaning that almost every single patient who got the drug and had a median of six prior lines of therapy had reduction in tumor size. And that's unreal. I think it was revolutionary in the sense that we had never seen that kind of activity in such a pretreated population. The agent was studied in other registration trials, DESTINY-Breast03, which looked at T-DXd and compared it head to head with T-DM1 in a predominantly second-line metastatic HER2-positive population, and here, again, unprecedented results. I've never seen a p value like that or a hazard ratio of, again unreal, of a little under 0.3 and seeing a 28-month PFS with T-DXd relative to just a little under 7 months PFS with T-DM1. We have never seen patients with metastatic HER2-positive breast cancer have a PFS that long. Even in CLEOPATRA, it's a little under 19 months in the first-line setting, where people were predominantly naïve to HER2-directed therapies. This, again, is really changing outcomes for patients. But then, I think, when we go to the next step, we studied T-DXd in patients with HER2-positive breast cancer and it had again these unprecedented results. But there was some early data suggesting that it could even work in tumors that weren't truly HER2-positive but what we call HER2-low, meaning that they weren't HER2/3+, they weren't HER2-0 but they were 1+ to 2+ and not FISH amplified. And so even with a little bit of protein there, they were seeing activity in the early phase studies and so it led to DESTINY-Breast04, which compared T-DXd to chemotherapy of physician's choice in people who had had one or two prior lines of chemotherapy in the metastatic setting. It was predominantly geared to look at outcomes in hormone receptor-positive breast cancer. But there was a small group of 58 patients with triple-negative disease that were also included in that trial. And here again, a very unprecedented outcome seeing a response rate of about 50%, which, again, we never see in pretreated hormone receptor-positive disease. And a PFS of 10 months, and again, these are people who already had one or two prior lines of chemotherapy. So it's, again, really changing outcomes. And so now I think it leads us to a lot of other questions that we are addressing in trials - can this drug work even if the tumor has maybe no HER2 expression, what about HER2-0, what about HER2-ultra low, meaning a little bit of staining but not quite 1+. And so these are questions that I think we will need to address and there are studies that will help us address that. On the flip side, we saw sacituzumab govitecan get developed in breast cancer. Initially, we saw very impressive results from a single arm study of sacituzumab in metastatic triple-negative disease where we saw response rates of a little over 30%. These are patients who were very heavily pretreated with metastatic triple negative breast cancer where, unfortunately, response rates end up being in a 5% range so it was a home run in that setting. So that led to the ASCENT trial, which compared sacituzumab govitecan to treatment of physician's choice therapy and that study really enrolled people who were, in essence, second line and beyond in the metastatic triple-negative setting and showed almost triple progression free survival, in essence, doubled overall survival. So again, very robust efficacy leading to confirming its approval. And then we saw data from TROPiCS-02, which looked at sacituzumab in metastatic hormone receptor-positive disease and also showed improvements in both progression free and overall survival. And this was in pre-treated populations of 2 to 4 prior lines of chemotherapy. These agents, again, have established robust efficacy, and so now the idea is can we move these drugs earlier in development into earlier line settings and can we even move these agents into the early disease setting and potentially cure more patients? So hopefully, we'll figure out ways to make that happen. Dr. Hope Rugo: Yeah, that was a great summary of this exciting data. And I think we really got an idea of what waterfall plots could tell us from DESTINY-Breast01 where you could count the number of patients whose cancers grew with therapy on one hand. It's been a huge advance. I think it's where we get this “revolution” even in patients with a median of 4 lines of prior chemo, and, in the ASCENT trial, we were able to see this improvement and survival in the hardest-treated subset of metastatic breast cancer triple negative disease. And then the remarkable data in HER2-positive and HER2-low breast cancer hormone receptor positive disease. We're really covering all of the subset of breast cancers. When we introduce new therapies though, and of course, our interest is moving them earlier as lines of therapy in the metastatic setting, we really have to think about the adverse events and how those are going to affect their patients, and balancing the risk benefit ratio. Obviously when the benefit is so huge, we're more thinking about how do we proactively manage these side effects, educate our patients, use prophylaxis when possible. Can you share with us some of your insights on management strategies for toxicities? Dr. Sara Tolaney: You bring up a very good point, and I will say the ADCs were designed with the idea being that we could deliver a ton of chemotherapy into a cancer cell. So obviously, my hope had been that we weren't going to see a lot of chemotherapy-like side effects because the goal was to try to spare normal cells of these side effects. But unfortunately, we do see that these agents do have real toxicities, and I think that is an important message. So, for example, with sacituzumab, for people who have hair going into it, they will lose their hair during the course of treatment, and so that's important to make patients aware of. It can lower blood counts, and about 50% of patients who are on sacituzumab will end up needing growth factor support while they're on treatment. So, that is again something that needs to be monitored and managed. But usually, we're pretty good at managing neutropenia, and with the growth factor support, I find that it actually works really well. Another thing with sacituzumab is the potential risk of diarrhea, but most of the diarrhea is low-grade diarrhea. It's rare that you get someone who has high-grade diarrhea with sacituzumab. Usually, I find it works to just instruct patients to use loperamide as needed. And again, usually that works well. And certainly when needed, dose modification can also help with these side effects and so it is important to keep in mind that this is another option. With T-DXd, one thing that we do have to keep in mind as an unusual side effect is the potential risk of interstitial lung disease. We see that in about 10% to 15% of patients getting T-DXd. That is something that we do have to be very mindful of. For the most part it is low-grade ILD. But there are rare occasions where there have been deaths from ILD. And we're seeing with some of the newer trials, the death rate is usually under 1%, but it is a real potential risk. And so it is really important to counsel patients when getting T-DXd about this potential side effect, that way they are good about communicating with you if they get any new symptoms, such as shortness of breath or dry cough, to get you aware of it and can work it up and get imaging certainly if that occurs. And then I think the management for ILD is a little unique and a little different truthfully than the way we manage pneumonitis from other drugs. Normally, when I am treating patients who develop pneumonitis, even if it is mildly symptomatic, we often will hold treatment, give steroids, and rechallenge them when it gets better. But with T-DXd, if anyone develops symptomatic pneumonitis, you actually have to permanently discontinue the T-DXd per the guidelines because we just don't know the safety of being able to rechallenge that patient once that pneumonitis resolves. For grade 1 ILD, meaning someone who has, for example, ground glass changes seen on imaging but doesn't have any symptoms, you have to hold the drug and wait until those imaging findings resolve and then you can restart. I usually do treat grade 1 ILD patients with steroids with the hope being that maybe it will allow for the pneumonitis to resolve more quickly, although in truth I don't know if that's the case. I have just taken that approach because I don't like leaving patients off the drug for too long if not needed. Again, I typically treat them with steroids, reimage in three to four weeks, and see if I'm able to restart. If they resolve within 28 days, you can restart at the same dose. If it takes longer to resolve, you need to dose modify. And then I think the other big thing with T-DXd is to know that it is categorized as a highly emetogenic agent. Most of us are using three-drug prophylaxis, which I think works really well. It is also important to realize that there can be some delayed nausea, which is a little unusual with some of our other agents. And so to warn patients about that and I find that use of olanzapine or ondansetron for the delayed nausea tends to work pretty well. Hope, do you have any pearls for us? Obviously, you are very experienced in using these agents; are there any things you would recommend for the management of ADCs? Dr. Hope Rugo: Yes, it's such a great question and an important area because, particularly as we are using these agents earlier, we really need to have strategies for both how long to continue as well as manage the toxicities. I agree with the nausea, olanzapine has been really a great addition, and using a triplet as initial premedication makes a big difference for T-DXd and other deruxtecan ADCs that are in the pipeline. And then I think that the ILD issue, we're really learning more about the risk factors as well as retreatment. And hopefully, we'll have more data this year at ESMO Breast and maybe ASCO on retreatment for grade 1. We certainly now do not have any data on the safety of retreatment for grade 2, so that is really not accepted now. For sacituzumab, I think the interesting area is the metabolism and the impact. So with neutropenia, as we move the drug earlier, it's easier and easier to manage, we see less severe neutropenia. We can give growth factors, which we are all good at in oncology. But I think the question about managing diarrhea and who is at risk still exists. Understanding pharmacogenomics and UGT1A1 is an interesting area where patients who have diarrhea could be tested to see if they are poor metabolizers which affects a little under 10% of the overall population. Because in that group, you could give less drug and get the same benefit with less toxicity. So I think this is all very interesting. It is important for providers and patients to be educated so that we can manage this appropriately. And I think you gave an excellent overview. We have new agents in the pipeline also and maybe we'll talk about those next, and then we'll talk a little bit about sequencing and resistance, as well as the unmet need for brain metastases. So lots of areas to talk about. There are a number of TROP-2 ADCs that are in the pipeline, and one that has presented phase III data, datopotamab deruxtecan. But other studies are being developed with new TROP-2 ADCs as well. But then there are a huge number of ADCs there with new targets, for example, immune effector targets, and new payloads, even immunotherapy and two different payloads or bispecific antibodies. And then there is interest in combining ADCs with immunotherapy and PARP inhibitors. We saw data in bladder cancer, I think it was bladder cancer, with combined 2 different ADCs at ESMO in 2023. So a lot of new approaches. How are we going to manage this moving forward? And where do you think we are going to position some of these next sort of "me-too" drugs? Dr. Sara Tolaney: It's an excellent question, and you're right, the field is exploding with new antibody- drug conjugates. So, it's going to leave us with this conundrum of what to do. And you brought up the really interesting example of the fact that we have an approved TROP-2 ADC, we have as sacituzumab govitecan, and for example, we've recently seen some really exciting data come out from TROPION-Breast01 looking at another TROP-2 ADC, datopotamab deruxtecan or Dato-DXd where that ADC performed better than chemotherapy in a head-to-head trial in terms of progression-free survival in a hormone receptor-positive population. Then there's another TROP-2 ADC, moving forward in development moving to phase III that Merck is developing MK-2870. All three of these ADCs are targeting TROP-2 and have a TOPO 1 payload. So, it leaves you with the question of how do you think about that? Is there going to be a role for using serial TROP-2 ADCs? Could one work after the other, even when they have very similar payloads? How are we going to incorporate them? How do you pick one over the other? So, it is going to be tricky for us as we get more and more of these agents. I think we're all excited about seeing ADCs that may have different targets and different payloads, where maybe we will see that sequential utilization will have robust efficacy if we swap things out. Again, we don't have data here yet, but I think there are other agents in development. For example, you could think of like, disitamab vedotin targets HER2 and has an MMAE payload. So, could it be that someone progresses on T-DXd for HER2-low, but then could go on to disitamab vedotin? How will that work? So, we have a lot to learn, but it's really nice to have so many options. Dr. Hope Rugo: Yeah, it'll be interesting to see whether or not we select the ADC based on a rational understanding of the tumor and the patient, or whether it's simply what's easier to give and has the right toxicity for that patient. So, that sort of brings us to our next topic, which is how are we going to sequence these agents? How are we going to understand the mechanisms of ADC resistance? At San Antonio in 2023, we saw a presentation where there was a top-alteration, and the patient had a really long response to a top-directed ADC, or an agent that carried a topoisomerase inhibitor. And that really struck me that we're going to see these alterations. There was a fresh autopsy study that suggested that the alterations may be different in different organ sites of disease. How are we going to figure this out? Dr. Sara Tolaney: Yeah, I also was really puzzled to see those data from San Antonio where we've sort of simplified ADC resistance in our heads to say, well, maybe someone becomes resistant because they lose target expression, or maybe someone becomes resistant because they've developed resistance to the payload, kind of like the way we think of someone developing resistance to getting chemotherapy. But obviously, it's probably far more complex than that. With these ADCs, they need to be able to internalize the ADC and could there be mechanisms of resistance related to the internalization process? So, I think there are lots of potential areas where resistance could be occurring. I think, we don't understand it very well. We've seen patients, for example, who have responded. This is just anecdotal, but we have data, for example looking at, Dato-DXd in the phase 1 triple-negative study where there were some patients who responded despite having progressed on sacituzumab. Well, why is that? You would think if it's target resistance or payload resistance, it would be the same target and a very similar payload. So, why would those drugs work one after the other? And that's why I think we just don't understand this well enough at this point in time. So, it's clearly an area where more research is needed because it does have significant implications on how we think about using these drugs sequentially. We will need to understand these resistance mechanisms because there do seem to be some rare patients who benefit from these sequencing strategies and then others who don't. So, it would be nice to be able to figure this out and hopefully in the future, we'll be able to test patients and know what drugs to give them. But I think we're far off from that, unfortunately, right now. Dr. Hope Rugo: Yeah, it does seem to be a relatively elusive approach, and I think, in part, it's due to the heterogeneity of cancer. And maybe, as we're better and better at analyzing tumor cells in the blood, which are a rare group, and ctDNA, which, of course, we do now to look for mutations, maybe that'll be an approach that we'll be able to take. And also, of course, moving the drugs earlier into the disease setting with less heterogeneity and mechanisms of resistance might help as well. I was fascinated by the fact that although the PFS to the first ADC seems to be overall much greater than the PFS to the second ADC, when you sequence them, there are a few patients who have a longer PFS with the second, even if these are just sacituzumab T-DXd sequencing in various directions. So, it's clearly very complex. And right now, I think we're just sequencing and we don't really know how to do it. We just choose what we think is best for that patient first and go on to the next one later, which is interesting. And one of the choices might be treating brain metastases, which of course remains a huge unmet need. And if we could find effective treatment for brain metastases, maybe we could also prevent them in some patients more. What do we know about the central nervous system (CNS) penetration of ADCs and the clinical results? Dr. Sara Tolaney: At first, we were not optimistic that these drugs would have activity in the brain because we thought that these were very large agents that probably couldn't penetrate into the blood-brain barrier. But in fact, I think we were all very excited to see that there is actually data suggesting that these drugs can actually have robust efficacy in the CNS in patients who have active brain metastases. And so what we've seen so far is data with trastuzumab deruxtecan or T-DXd, there have been some trials that have been done, including studies like DEBRA and TUXEDO, which have looked at T-DXd in patients who have active brain metastases and are showing very robust response rates within the CNS. So, we're seeing intracranial response rates on the order of 40% to 50%. And clinically, this is what we're seeing as well. These are smaller studies and there's a larger trial, DESTINY-Breast12, which will hopefully validate the robust efficacy in the CNS with T-DXd. So, again, it's really nice to see this. To your point, though, one area that I'm curious about, as you were alluding to, is will these drugs be able to prevent CNS disease? And I think that is a very different question because here the blood-brain barrier is not intact when patients have progressive brain metastases, and so these ADCs are causing robust activity. But if you look, for example, and I'll be curious to see what happens, DESTINY-Breast05 is looking at T-DXd in the post preoperative setting for patients who have residual disease and comparing it to T-DM1. And unfortunately, we saw that T-DM1 was not able to prevent brain metastases when looking at data from KATHERINE, where in fact, rates of CNS as the first site of recurrence were similar with T-DM1 and trastuzumab. So, now we'll be interested to see, will it be any different with T-DXd? Will T-DXd be able to have any role in prevention? I think we haven't seen anything like that with ADCs to date, so that would be a paradigm shift in our way of thinking. Right now, there are strategies being taken from a prevention standpoint of trying to add a tyrosine kinase inhibitor in that early-stage setting, such as what is being done in the COMPASS-RD trying to add tucatinib to T-DM1 to see if that would do it. But again, we really need to understand, again, how these drugs work, particularly when the blood-brain barrier may not be intact. But again, very exciting data with T-DXd in an ongoing trial, actually through SWOG looking at sacituzumab for patients with CNS disease. And we've seen some preliminary data with sacituzumab showing that it actually does penetrate into the brain when they've looked at drug levels in the tumor in the brain, comparing it to plasma, it actually looks similar. So, we know it's getting in there and we'll have more robust efficacy data, hopefully coming soon. Dr. Hope Rugo: Yeah, that was a great summary of that data. It's been exciting also to see some responses in patients with leptomeningeal disease as well, where we've really been struggling with anything that works for more than a few weeks or months at the most. So I'm holding out great hope that we're going to see a big difference because even though TDM-1 had some efficacy, it was nothing like what we're seeing with T-DXd. So we'll see. And the same with sacituzumab with triple negative disease, where sometimes brain metastases can be an isolated site of recurrence, even in patients who have a pathologic complete response. So it has been a big challenge. So I think that what we've learned from you is a lot about the mechanisms and the data about these new ADCs, the tremendous hope that these are bringing to our patients, but also the really exciting new approaches with new payloads, new targets of drugs that are in development, as well as potentially some different ADCs that have the same target and similar mechanisms of action of this payload. Really fascinating to hear about this, the future work on sequencing, on mechanisms of resistance, and on brain metastases. We have, of course, 2 prospective trials that we'll be looking at sequencing, one with T-DXd and Dato-DXd, and one registry trial with T-DXd and sacituzumab govitecan in the US. So that's also going to, I think, provide us with some important information. We could talk for a long time about this, but I just wonder if you have any closing comments to sum up your thoughts. Dr. Sara Tolaney: I think you did a great job leading us through thinking about ADCs, and I think it'll be really interesting to see what happens in the future. While again, these agents have become a standard for us for patients with metastatic disease, I'm going to be curious to see how everything evolves and to see if we'll be able to substitute chemotherapy with ADCs in early disease settings and change outcomes. Will we be able to have novel combinations? Will we be able to sequence these drugs one after another? Will we actually have biomarker predictors to help us sort out which drug to give when? So, still a lot to learn, but clearly a very exciting field right now. Dr. Hope Rugo: Indeed. Sara, thank you for sharing your valuable insights with us today on the ASCO Daily News Podcast on your great work to develop novel therapies for breast cancer. It's always a pleasure to talk to you, and even greater to work with you on the future progress of treatment for breast cancer. Dr. Sara Tolaney: Thank you so much, Hope. Again, really nice to always discuss these data with you. I always learn a lot, so thank you. Dr. Hope Rugo: Thank you. And thank you to our listeners for joining us today. You'll find a link to all of the studies 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 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 a product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers: Dr. Hope Rugo @hoperugo Dr. Sara Tolaney @stolaney1 Follow ASCO on social media: @ASCO on Twitter ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. Hope Rugo: Consulting or Advisory Role: Napo Pharmaceuticals, Puma Biotechnology, Mylan, Eisai, Daiichi Sankyo Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Genentech, Merck, Daiichi Sankyo, Sermonix Pharmaceuticals, AstraZeneca, Gilead Sciences, Astellas Pharma, Talho Oncology, Veru, GlaxoSmithKline, Hoffmann-LaRoche AG/Genentech, Inc, Stemline Therapeutics Travel, Accommodations, Expenses: Merck, AstraZeneca Dr. Sara Tolaney: Consulting or Advisory Role: Novartis, Pfizer, Merck, AstraZeneca, Genentech, Eisai, Sanofi, Bristol-Myers Squibb, Seattle Genetics, CytomX Therapeutics, Daiichi Sankyo, Immunomedics/Gilead, BeyondSpring Pharmaceuticals, OncXerna Therapeutics, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics, Umoja Biopharma, Menarini/Stemline, Aadi Bio, Artio Biopharmaceuticals, Incyte Corp, Zetagen, Bayer, Infinity Therapeutics, Jazz Pharmaceuticals, Natera, Tango Therapeutics, Systimmune, eFFECTOR Therapeutics, Hengrui Pharmaceutical (USA), Sumitovant Biopharma Research Funding (Inst.): Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Bristol-Myers Squibb, Eisai, AstraZeneca, NanoString Technologies, Seattle Genetics, OncoPep, Gilead Travel, Accommodations, Expenses: Eli Lilly, Sanofi, Gilead Sciences

SABCS 2023 HER2+ Breast Cancer Highlights – APHINITY Sub-analysis, KATHERINE update, HER2CLIMB-02

Oncology Brothers

Play Episode Listen Later Jan 11, 2024 14:34

In discussion with Dr. Daniel G. Stover, covering the San Antonio Breast Cancer Symposium 2023 Highlights from Community Oncology perspective. We covered 3 important practice informing studies in HER2+ disease with Dr. Stover: - APHINITY Sub-analysis: Benefit of Adj Pertuzumab and Trastuzumab According to ER and HER2 Expression - KATHERINE Update: Phase III Study of Adjuvant TDM-1 vs Trastuzumab for Residual Invasive HER2-positive Early Breast Cancer After Neoadj Chemo: Final IDFS and Updated OS analysis - HER2CLIMB-02: Randomized, Double-blind Phase 3 Trial of Tucatinib and TDM1 for Previously Treated HER2-positive Metastatic Breast Cancer

er trial phase benefit breast cancer randomized her2 metastatic breast cancer trastuzumab san antonio breast cancer symposium community oncology t dm1

Systemic Treatment of Patients with Metastatic Breast Cancer Resource-Stratified Guideline

Oncology Peer Review On-The-Go

Play Episode Listen Later Jan 10, 2024 19:03

Dr. Banu Arun and Dr. Sana Al Sukhun share recommendations from the newest ASCO resource-stratified guideline on systemic treatment for patients with metastatic breast cancer. They describe the importance of this new guideline, the four-tier resource setting approach, key recommendations, and implementation considerations. Recommendations are discussed for systemic therapy for HER2-positive, triple-negative, and hormone receptor-positive metastatic breast cancer, across Basic, Limited, and Enhanced resource settings. Drs. Arun and Al Sukhun highlight the importance of this guideline for clinicians and patients in regions with limited resources to optimize cancer care. Read the full guideline “Systemic Treatment of Patients with Metastatic Breast Cancer: ASCO Resource-Stratified Guideline” at www.asco.org/resource-stratified-guidelines." TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/resource-stratified-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest disclosures in the JCO Global Oncology, https://ascopubs.org/doi/10.1200/GO.23.00285 Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one at asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Banu Arun from the University of Texas MD Anderson Cancer Center in Houston, Texas, and Dr. Sana Al Sukhun from Al Hayat Oncology Practice in Amman, Jordan, co-chairs on “Systemic Treatment of Patients with Metastatic Breast Cancer: ASCO Resource-Stratified Guideline.” Thank you for being here, Dr. Arun and Dr. Al Sukhun. Dr. Banu Arun: Thank you for having us. Dr. Sana Al Sukhun: Thank you. Pleasure to join you. Brittany Harvey: And before we discuss this guideline, I'd just like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including the guests who have joined us today on this episode, are available online with the publication of the guideline in the JCO Global Oncology, which is linked in the show notes. Then, to jump into the content of this guideline, Dr. Al Sukhun, can you first provide an overview of the scope and the purpose of this guideline? Dr. Sana Al Sukhun: Sure. And again, thank you, Brittany. Pleasure to join you. This guideline is really interesting and very important. It addresses the care and treatment of the most common cancer worldwide, particularly metastatic breast cancer, taking into consideration different availability of resources, particularly in countries with limited resources. As you know, most of us are aware of the importance of clinical practice guidelines improving outcomes for patients in medicine, not only in oncology, but most of those guidelines are developed in countries that are highly resourced. So their applicability in countries of limited resources that lack infrastructure and resources is definitely limited because they cannot really adopt and adapt to those guidelines, which makes resource adapted or resource stratified guidelines quite important and helpful. First, to clinicians caring for patients so that they can properly allocate resources, prioritize how to use therapy for patients, but also even policymakers to allocate resources and plan graduated implementation of science to improve outcomes for their patients according to the progressive availability of resources. So we're talking about breast cancer, the most common cancer worldwide. And not only is it the most common cancer worldwide, but also more than two-thirds of new cases are diagnosed in countries of limited resources. Unfortunately, they also carry the burden of more than 70% of the mortality attributed to breast cancer. Another challenge is that the median age for the patients affected with breast cancer in countries of limited resources is indeed at least a decade younger than Western societies, which adds to the burden, not only the social, but also the economic burden of cancer. And unfortunately, presentation in these countries is mostly locally advanced, metastatic breast cancer, therefore comes the focus on helping our colleagues in countries of limited resources to care for patients according to the resources available, not only in countries of limited resources, even colleagues practicing in less fortunate areas within countries that are highly resourced. Brittany Harvey: Excellent. Thank you for providing that background information for this guideline. So then you've just described how many countries and areas have different resources. So, Dr. Arun, could you describe the four-tier resource setting approach that this expert panel used? Dr. Banu Arun: Yeah, Brittany, that's a good question. I think it's important to know where we started and what infrastructure we used. So for developing resource stratified guidelines, ASCO has adopted its framework from the four-tier resource setting approach, which was actually developed by the Breast Health Global Initiative, and we employed modifications to that framework based on the disease control priorities. What this framework emphasizes is also that variations can be present not only between countries, but actually within countries with disparities, for example, differences between rural and urban areas within one country. So the four settings are obviously basic, limited, enhanced, and maximal settings. The basic setting includes core resources or fundamental services that are really absolutely necessary for any public health, primary health care system to function at all. These include services that are typically applied in a single clinical interaction. For example, vaccination is feasible for highest need populations. The next tier would be the limited setting. That includes countries or settings with second-tier resources or services that are intended to produce major improvements in outcomes, such as incidences and cost effectiveness. Unlike the basic setting, it can involve single or multiple interactions with providers or healthcare services. Then the third tier is the enhanced setting, where the services are optional but important, and these services should ideally produce further improvements in outcome and increase the number of quality of options and also individual choices, maybe countries having the ability to track patients and links to registries. And then the last one is of course, the maximal setting that includes high-level, state-of-art resources and services that are available in some high-resource countries. Brittany Harvey: Thank you for describing that framework and the approach that the panel used. So then I'd like to move on and talk about the key high-level recommendations of this guideline for systemic therapy for metastatic breast cancer across those three lower tiered resource settings - the basic, limited, and enhanced resource settings. So, Dr. Al Sukhun, could you start with the recommendations across these settings focusing on HER2-positive breast cancer? Dr. Sana Al Sukhun: Sure. You know, HER2-positive metastatic breast cancer is one of the most aggressive subtypes of breast cancer. However, its outcome has been transformed with the introduction of HER2-targeted therapy. So, apart from patients who suffer from congestive heart failure or limited compromised ejection fraction, which can be evaluated on a case-by-case basis, patients are candidates for HER2 targeted therapy. When we made the recommendations according to the availability of resources, we started in a gradual approach. So, in a maximal setting, you treat patients with HER2-positive metastatic breast cancer in the frontline setting using the combination of trastuzumab, pertuzumab, and taxanes or endocrine therapy if patients have limited disease burden, or if they have the recurrence after a long disease-free interval. Usually, the combination of trastuzumab and pertuzumab with taxane is used. But then again, clinicians can use navelbine, considering good data from the HERNATA trial about its efficacy as compared to taxanes and even also, we recommended platinum therapy according to availability. However, if pertuzumab is not available, you go to the next level where we recommend offering, again, chemotherapy, be it taxane, navelbine, platinum, with trastuzumab, or even without trastuzumab if trastuzumab is not available. So, something to keep in mind, chemotherapy is not without efficacy in this aggressive subtype. It is not as good as when you use the combination with HER2-targeted therapy, but it still works. Patients and clinicians in this era of biologic therapy immunotherapy tend to think only pricey medications are the ones that can be used for treatment and improving outcome. However, definitely adding help with targeted therapy is great whenever it's available. But if it's not available, chemotherapy still could be used in a sequential manner. We listed all possible chemotherapeutic options starting with taxanes, navelbine, platinums, even CMF, capecitabine. When it comes to second-line therapy, including those patients who relapse within 12 months of adjuvant therapy, the optimal line of treatment would be trastuzumab deruxtecan. However, if it's not available, we recommend to be offered with successive or progressive preference, if it's not available, T-DM1 could be used. If it's not available, capecitabine and lapatinib could be used. If it's not available, trastuzumab with chemotherapy could be used. If it's not available, we go back to the sequential use of chemotherapy, including adriamycin, taxanes, platinums, capecitabine, or even CMF. Brittany Harvey: I appreciate you reviewing those recommendations for HER2-positive breast cancer. So then, moving along, Dr. Arun, what are the recommendations for patients with metastatic triple-negative breast cancer? Dr. Banu Arun: Thank you, Brittany. Triple-negative breast cancer, of course, is one of the serious subgroups of breast cancer. About 10 to 15% of patients have triple-negative breast cancer. What I will do is I will divide it into the three-tier settings as well as first-, second-, and third-line therapies. For patients with triple-negative PD-L-negative metastatic breast cancer in the limited settings and even enhanced settings, single-agent chemotherapy rather than combination chemotherapy should be recommended as the first-line. However, if patients are symptomatic or have immediate life-threatening disease, combination chemotherapy can be offered. For patients with triple-negative breast cancer that are PD-L1 positive, they may be offered in addition to chemotherapy, an immune checkpoint inhibitor, as first-line therapy, most probably in enhanced settings and in basic and limited, of course, chemotherapy. When you move on to the second-line for metastatic breast cancer in patients with or without previous PD-L1 checkpoint inhibitors, clinicians can offer palliative or best supportive care in the basic setting. In the limited setting, chemotherapy with anthracyclines, taxanes, platinums are options. And in the enhanced setting if sacituzumab govitecan is not available, chemotherapy would be an option. Now, when we move on to the third-line setting for triple-negative breast cancer, clinicians can actually offer chemotherapy and/or palliative care, depending really on the status of the patient. Brittany Harvey: Excellent. Thank you for providing those recommendations for triple-negative breast cancer. As you mentioned, it's one of the rarer forms of breast cancer. So then, Dr. Al Sukhun, I'd like to move into the last section of patients, actually the most common, but hormone receptor-positive breast cancer. What are those recommendations? Dr. Sana Al Sukhun: Thank you, Brittany. As you mentioned, it's the most common subtype worldwide. The rule of the thumb is sequential hormonal therapy, depending on availability. So, whatever you have hormonal therapy, sequential hormonal therapy unless pending visceral crisis or symptomatic disease, it's recommended that you offer sequential single-agent chemotherapy, unless it's a real visceral crisis, where we recommend combination chemotherapy. That's a classic in all our guidelines. When considering frontline hormonal therapy, again, I will start from the maximal level and gradually recommend according to availability. So in enhanced levels in many countries now, we have generic CDK4/6 inhibitors, which increase their availability. So we do recommend hormonal therapy with CDK4/6 inhibitors. Upon progression or when they are not available, on progression, you move to the second line of hormonal therapy. If you have liquid biopsy, check for PIK3CA mutation. Sometimes you do have the liquid biopsy, but you do not have alpelisib to offer to your patients with hormonal therapy, then it's okay, you still can move to second-line fulvestrant with everolimus. Sequentially, you can move forward to fulvestrant by itself if you do not have everolimus. And even you can sequence tamoxifen until your patient stops responding to hormonal therapy then you can offer sequential single-agent chemotherapy. Brittany Harvey: Thank you, Dr. Al Sukhun for providing those recommendations. So then, Dr. Arun, what should clinicians do when we do not have access to receptor assessment? What is recommended for best practices for management of those patients? Dr. Banu Arun: So, Brittany, that's an important question. There are some basic settings where unfortunately, immunohistochemistry for ER/PR HER2neu determination is not available. Our group really recommends in these cases that clinicians may presume hormonal receptor positivity and offer tamoxifen in most cases. It is expected that IHC would be available in limited and, of course, enhanced settings. Brittany Harvey: Great. Thank you for providing that information. So further, what else should clinicians know as they implement these recommendations, Dr. Arun? Dr. Banu Arun: It's very important that we, all healthcare provider clinicians, really know the data. I think reading the guidelines or knowing about first and second line therapies is obviously important, but the devil is in the details. And I think knowing the publications and subgroup analyses, if needed, because every patient is different and sometimes the recommendations cannot go by the books. You really need to do an assessment of the patient and see in which setting you are and then make the most of the guidelines that are recommended. It's to guide. The name is guidelines. It's to guide. And ultimately, it's the clinician's responsibility to find the best available therapy for the patient. And sometimes that includes no treatment and supportive care. Dr. Sana Al Sukhun: Totally agree with Dr. Arun. They are there to support the clinician decision. After all, the clinician is the one who sees the patient, who can evaluate the patient from all aspects — social aspect, physical aspect, the tumor aspect. So it's not just about the tumor, it's about the patient and the environment where the clinician is treating the patient. However, I believe there is support to the clinician not only in treating the patient, but also on addressing priorities for research to improve outcomes for patients in different resource settings. There is also support for the clinicians to help them advocate for improving care for patients in a strategic way, where they prioritize resource allocation. So they are there to support the clinician at all levels, not only when treating patients, but when advocating for patients, when helping patients to make decisions, when they're discussing with their health officials and policymakers. Brittany Harvey: Absolutely. Those are excellent points that you both made about individualizing patient care for the specific person in front of you. So then, finally, Dr. Al Sukhun, how will these guideline recommendations impact patients with metastatic breast cancer globally? Dr. Sana Al Sukhun: The ultimate goal for anything we do, including guidelines, is to improve outcomes for patients worldwide. They are there to support clinician decisions, empower clinicians to optimize care for their patients, to advocate for improving outcomes for patients by strategically allocating resources according to the most impactful strategy. They help clinicians to identify areas for research that are needed according to the resources available to them. They are there to guide policymakers, again, also implementing strategies to implement science that could improve outcomes in an efficient way for their societies. So hopefully, all these, with our research, with our advocacy, with our health policy, with our treatment decisions, hopefully all these will improve outcomes for breast cancer patients and ultimately reduce mortality, particularly in less fortunate, limited resource settings for patients everywhere. Brittany Harvey: Absolutely. We hope that these guidelines improve outcomes and quality of life for patients worldwide. So I want to thank you both so much for your work to develop this guideline. There's certainly a large amount of recommendations, so I encourage our listeners to read the full guideline, which is linked in the show notes. And I want to thank you so much for your time today, Dr. Al Sukhun and Dr. Arun. Dr. Sana Al Sukhun: Thank you for having us. Dr. Banu Arun: Thank you, Brittany. Brittany Harvey: And thank you to all of our listeners for tuning into the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/resource-stratified-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

S1 Ep91: HER2CLIMB-02 Trial Shows ‘Interesting Data' in HER2+ Breast Cancer

Play Episode Listen Later Jan 9, 2024 12:33

In a recent conversation with CancerNetwork®, Sara A. Hurvitz, MD, FACP, senior vice president and director of the Clinical Research Division at Fred Hutch Cancer Center and head of the Division of Hematology and Oncology at the University of Washington Department of Medicine, discussed new treatment options for patients with metastatic HER2-positive breast cancer. In the discussion, Hurvitz highlighted findings from the phase 3 HER2CLIMB-02 trial (NCT03975647), which assessed the efficacy and safety of tucatinib (Tukysa) plus ado-trastuzumab emtansine (Kadcyla; T-DM1) in patients with HER2-positive breast cancer, specifically those with brain metastases. Patients enrolled in this trial experienced a significant improvement in progression-free survival (PFS) with the tucatinib-based regimen. Data presented at the 2023 San Antonio Breast Cancer Symposium (SABCS) highlighted that the median time to disease progression or death was 9.5 months (95% CI, 7.4-10.9) and 7.4 months (95% CI, 5.6-8.1 in the experimental arm and placebo arm, respectively (HR, 0.76; 95% CI, 0.61-0.95; P = .0163). In patients with brain metastases, the median time to disease progression or death was 7.8 months (95% CI, 6.7-10.0) and 5.7 months (95% CI, 4.6-7.5) in the experimental arm and placebo arm, respectively (HR, 0.64; 95% CI, 0.46-0.89). Investigators reported that toxicity in the experimental arm was generally manageable and reversible. “This was a study that only enrolled patients who were naive to trastuzumab deruxtecan [T-DXd; Enhertu],” Huvitz said. “We know that T-DXd has substantial improvements in PFS and survival, so having so many patients receive this [agent] after progression is certainly going to impact our ability to observe survival differences. About 15% of patients in each arm also went on to receive tucatinib. These are pretty exciting results for our patients, especially those with brain metastases. This study did enroll, as I said, patients with brain metastases, who comprised 44% or so of the entire population enrolled in this study. These are interesting data, and we'll see if this regimen is ultimately approved.” Reference Hurvitz SA, Loi S, O'Shaughnessy J, et al. HER2CLIMB-02: randomized, double-blind phase 3 trial of tucatinib and trastuzumab emtansine for previously treated HER2-positive metastatic breast cancer. Presented at the 2023 San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio, TX. Session GS01-10.

university data medicine trial patients md tx san antonio breast cancer investigators oncology hematology her2 pfs washington department san antonio breast cancer symposium enhertu t dxd t dm1 clinical research division kadcyla

SONIA, NATALEE, and Other Advances in Breast Cancer at ASCO23

Play Episode Listen Later Jun 21, 2023 25:11

Drs. Allison Zibelli and Arielle Heeke discuss the NATALEE trial's novel approach to high-risk HR+ breast cancer, the potential of delaying CDK4/6 inhibitors in HR+, HER2-negative mBC to decrease toxicities and costs in the SONIA trial, and de-escalation strategies in HER2+ early-stage breast cancer. TRANSCRIPT Dr. Allison Zibelli: Hello. I'm Dr. Allison Zibelli, your guest host for the ASCO Daily News Podcast today. I'm an associate professor of medicine and a breast medical oncologist at the Sidney Kimmel Cancer Center at Jefferson Health in Philadelphia. My guest today is Dr. Arielle Heeke, a breast medical oncologist at the Levine Cancer Institute at Atrium Health in North Carolina. Today, we'll be discussing practice-changing studies and other key advances in breast cancer that were 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 transcripts at asco.org/DNpod. Arielle, it's great to speak with you today. Dr. Arielle Heeke: Thank you so much for having me. Dr. Allison Zibelli: Let's start with LBA500. This was the NATALEE trial of ribociclib and endocrine therapy as adjuvant treatment in patients with hormone receptor-positive HER2-negative early breast cancer. What are your key takeaways from the study, and how do you think this changes our approach to high-risk ER-positive breast cancer? Dr. Arielle Heeke: Yeah, this was definitely the study for which many of us were waiting to see the results. It was exciting to see the results come through so quickly. As you mentioned, the NATALEE trial was a phase 3 study that evaluated three years of adjuvant ribociclib at a dose of 400 milligrams, which is a little different than what we're used to in the metastatic space at 600 milligrams. But essentially, it randomized patients to receive this 400-milligram dose with their adjuvant aromatase inhibitor therapy versus just the standard of care adjuvant endocrine therapy in patients that are high risk with early-stage breast cancer. What made NATALEE somewhat unique is they defined high risk a little bit more broadly than we've seen in previous studies, such as monarchE. So, what I mean by that is NATALEE enrolled patients with stage 2 and 3 early-stage breast cancer. And notably, they allowed for patients that were lymph node-negative but had some other high-risk features, such as a grade 3 tumor or a grade 2 tumor with high-risk genomics, such as oncotype or a high Ki-67. So, by broadening who was eligible, NATALEE captured more patients at risk for recurrence. Of course, we know that recurrence is not specific for patients with lymph node-positive disease. We can see recurrence even with stage 1, but certainly, we start to see more recurrence risk as patients drift into stage 2 and stage 3. In the NATALEE study, the majority of these patients did receive prior chemotherapy, which I also think is interesting. We've kind of seen in the metastatic space that sometimes chemotherapy can augment patients' responsiveness to CDK4/6 inhibitors. But specifically in NATALEE, 88% of patients had received prior chemotherapy, and ultimately, about a third of the patients were lymph node-negative. So, diving into some of the results with this first analysis that we saw at ASCO, with the median follow-up for invasive disease-free survival of just 27.7 months, they were able to show that the risk for invasive disease was reduced by 25.2% with the addition of ribociclib plus endocrine therapy compared to endocrine therapy alone. And this three-year invasive disease-free survival rate was 90.4% for the combination therapy compared to 87.1% for endocrine therapy alone, which is an absolute difference of 3.3%. Additionally, patients treated with ribociclib and endocrine therapy had a 26.1% reduced risk for distant disease-free survival compared with endocrine therapy alone, and this was a rate of 90.8% for ribociclib with endocrine therapy compared to 88.6% with endocrine therapy alone, which correlates to an absolute benefit of 2.2%. They did show results for overall survival as well, but again, follow-up was just a median of 27.7 months. So, data was essentially immature to show any true overall survival benefit from this approach. And in fact, only 20% of patients had completed three years of ribociclib at this data cutoff. And as a reminder, again, NATALEE involved ribociclib for three years compared to two years, which we've seen with other studies in this space. Also, what was encouraging from NATALEE were the readouts for toxicities. Neutropenia is definitely a concern with this class of medication, and they were able to show that rates of neutropenia were overall lower than what we've seen in the pooled data in the metastatic space. And also that problematic QTc prolongation for which we have to get EKGs baseline two weeks and four weeks. They also showed that the likelihood of having QTc prolongation on this therapy was significantly less at that 400-milligram dose compared to 600. I think the key takeaway is yes, this drug is effective as adjuvant therapy, which is perhaps not surprising since we've seen such promising results in the metastatic space, but numerically not as striking as what we have at this point with adjuvant abemaciclib, but of course, this is a newer study. We hope to see that continued separation of the curves as we were fortunate enough to see with the abemaciclib data, but obviously we'll be looking for additional analyses from NATALEE. And then how this will change practice, of course, we'll have to wait to see if the therapy is approved for use in the adjuvant setting for early-stage hormone receptor-positive breast cancer, but it certainly will be a nice option for patients that struggle with GI toxicity kind of at baseline. But also, if they were previously on abemaciclib and were not able to tolerate due to the GI toxicity, this would be an option for them. Also, as mentioned, it's a broader patient population, so we can consider this perhaps for a patient with lymph node-negative disease. Although we will have to ask ourselves that just because someone meets eligibility for the NATALEE study, and if the therapy is ultimately approved, is it appropriate to give it to all those patients? Or do we need to still kind of think of this in the setting of the highest-risk patient, not just any patient with stage 2 plus disease? There was a lot of talk at the meeting, certainly about biomarkers and potentially using ctDNA to try to find these predictors of benefit from CDK4/6 inhibitor therapy, but obviously, still a long way to go before we can use that type of technology in this space. Dr. Allison Zibelli: Thank you. Staying on the topic of CDK4/6 inhibitors, everybody was excited about the SONIA trial, which was LBA1000, and this trial was asking if we can delay using CDK4/6 inhibitors for newly diagnosed ER-positive HER2-negative metastatic breast cancer as a way to decrease both toxicity and cost. Tell us about this study. Dr. Arielle Heeke: The SONIA trial was such a cool study to see, and the presenter reported findings in such a thought-provoking way. Really great to see this sort of work being done because I think we all wonder deep down in our gut, if more is more, or if we do need to kind of be a little bit more thoughtful about how we introduce these therapies certainly from a patient perspective. Patients that participate at ASCO [meetings] have been saying for years how important it is to consider the toxicities in terms of side effects, but also, of course, financial toxicities. So, it was great to see the SONIA trial at center stage. Essentially, as you mentioned, it was a study that randomized patients in the first-line setting with metastatic hormone receptor-positive breast cancer to receive either first-line CDK4/6 inhibitor therapy or second-line CDK4/6 inhibitor therapy. So basically, there was a mandated crossover, so patients that received the CDK4/6 inhibitor first-line did not receive a second line and vice versa. Patients that were randomized to receive their endocrine therapy as monotherapy first line went on to receive CDK4/6 inhibitor at second-line. And the second-line endocrine therapy was fulvestrant in both of those situations. We kind of run into this problem with patients now where we have so many therapies available to us that we don't typically run out of treatment options, but rather we run up against treatment toxicity or ultimate failure of the human body to keep up with the demands of ongoing therapy. So, again, while it's maybe somewhat attractive to start treatments earlier using things first-line rather than second-line or longer, just kind of post-CDK4/6 inhibitor progression, you know using this CDK4/6 inhibitor again with a different endocrine therapy backbone is probably not offering a meaningful benefit to that many patients. So this type of study is so necessary to really try to help us frame who needs those therapies sooner and longer or perhaps is there a substantial portion of patients that we don't need to put them through that sort of toxicity. So that's the SONIA trial. Some things to note about the patient population, these patients were a bit older than what we've seen in some of our metastatic CDK4/6 inhibitor trials. There was a median age of 64 and 87% were postmenopausal. Additionally, just 40% had received prior chemotherapy. And as is true for most of our studies, 91% have received palbociclib on study with just 8% receiving ribociclib. And the choice of the CDK4/6 inhibitor was per the treating provider, and at the time of the of study globally, palbociclib was the more commonly prescribed CDK4/6 inhibitor. But over the last year or so, data has certainly emerged favoring ribociclib in the metastatic setting. On the SONIA trial, patients were monitored for a median of 37.3 months. And looking at the primary endpoint of the second progression-free survival, which is defined as the time for random assignment to the second objective disease progression or death, for those patients who received first-line CDK4/6 inhibition, had a PFS2 of 31 months compared to 26.8 months with second-line CDK4/6 inhibitor use. And this slight difference was non-statistically significant. So the conclusion was that time to second progression was not impacted by whether or not a patient received first-line CDK4/6 inhibition or second-line CDK4/6 inhibition. Additionally, there were no differences in overall survival between the 2 arms with a median overall survival of 45.9 months with first-line CDK4/6 inhibitor use versus 53.7 months in second-line CDK4/6 inhibitor use. And that actually equates to significant differences in time on drug. The median duration of CDK4/6 inhibitor use with first-line therapy was 24.6 months compared to 8.1 months with second-line use. And by being on therapy for an additional 16.5 months if you use CDK4/6 inhibitor first-line, this, of course, leads to increased toxicity and certainly increased financial burden. And it was estimated that for each patient that receives this therapy first-line, there is an additional $200,000 spent on getting them the CDK4/6 inhibitor first-line, whereas the results from SONIA suggested that whether you use it first-line or second-line, the outcomes are essentially exactly the same. And then specific for the SONIA trial, by conducting the study, they saved approximately €25 million on drug expenditure during the conduct of the trial. It's just amazing when you take it to that scale. And then lastly just to mention, they looked at quality of life assessments as well and there were no differences in the two arms whether they got first-line or second-line CDK4/6 inhibition. Dr. Allison Zibelli: I thought this study was remarkable, and it got a long ovation when it was presented at the meeting. I'm certainly going to use this strategy and prioritize who needs upfront CDK4/6 inhibitor therapy. I think that we have to think of not just drug toxicity for our patients, but financial toxicity. A lot of these drugs have very high copays and the number one cause of bankruptcy in the United States is medical costs. So that's something we really have to keep in mind. I also thought it was very interesting that the study was designed in cooperation with the patient advocacy group and patients themselves were very enthusiastic about this study and helped design it and helped recruit to it. So all in all, I thought this was a remarkable study. So moving on, LBA1013 was the TORCHLIGHT study of toripalimab versus placebo in combination with nab-paclitaxel for patients with metastatic or recurrent triple-negative breast cancer. Many of us are not familiar with toripalimab. Can you tell us about the drug and how it was used in this study? Dr. Arielle Heeke: Yes, toripalimab is essentially an immunotherapy agent. It's an IgG4K monoclonal antibody that targets PD-1. In this study, TORCHLIGHT, patients were randomized to receive toripalimab versus placebo in combination with nab-paclitaxel in newly metastatic triple-negative breast cancer. The patients on study were randomized two to one to receive drug or placebo. The drug is given on day 1 of a 3-week cycle at 240 milligrams and then patients of course also receive nab-paclitaxel on a day 1 and day 8 schedule of a 21-day cycle. They did look at outcomes on the study based on PD-L1 positivity status and they assessed for PD-L1 with an IHC assay JS311 antibody that ultimately generated a combined positive score. And PD-L1 positivity was defined as a CPS of greater than or equal to one based off of this assay. In the study population, about a third of patients were- patients' tumors were CPS negative, a third had a CPS of 1 to 10 and about a quarter had a CPS of greater than or equal to 10. And then approximately 7% of the tumors had an unknown status. And then getting right into the results, we were provided results in the PD-L1 positive subgroup as well as the whole patient population. Looking at the primary endpoint of PFS, there were significant improvements seen in median PFS with the addition of toripalimab to nab-paclitaxel, again in the first line setting with a median PFS of 8.4 months with the addition of the immunotherapy agent versus 5.6 months with placebo. And this was statistically significant. And then in the intent to treat population, there were some numeric improvements, in median, progression-free survival at 8.4 months with the addition of toripalimab versus 6.9 months with placebo. We also got some results with overall survival that were quite intriguing, although this initial analysis was not designed to necessarily prove statistically significant differences in overall survival. But again, there were some promising trends. Looking first at the PD-L1 positive subgroup, the median overall survival was 32.8 months with the addition of toripalimab versus 19.5 months with placebo. Breaking it down a little bit further based on CPS values, for a CPS of 1 to 10, median overall survival was 32.8 months versus 19.5 months. And then for those very high CPS or greater than or equal to ten, median overall survival was not reached in this group versus 18.3 months with placebo. Also, looking in the intent-to-treat population, there were also improvements in overall survival with the addition of toripalimab with a median overall survival of 33.1 months with the addition of immunotherapy versus 23.5 months with nab-paclitaxel alone. So potentially, depending on next steps of this study, we would potentially have an option to add immunotherapy that is not biomarker specific, meaning we can potentially provide toripalimab to all patients regardless of their PD-L1 status. Dr. Allison Zibelli: Very interesting new drug to look forward to. So, one of the major themes of this year's meeting was de-escalation strategies. For example, LBA506 reported the three-year invasive disease-free survival of the PHERGain trial, which looked at eliminating chemotherapy for HER2-positive patients getting neoadjuvant therapy. Tell us about the design of this study and how will it impact the care of these patients? Dr. Arielle Heeke: The design was very complicated. I had to look at it a few times to really make sure I got my head around it. But I think once you do figure it out, you can see how there might be a path forward in clinical practice. Although I think for all of this work, it's maybe not ready yet for primetime, but certainly thought-provoking. But the PHERGain clinical trial, I feel like we've heard about this study for a little while and this concept of de-escalation really kind of started in the HER2-positive space. But this study was a randomized study of chemotherapy de-escalation and early HER2-positive breast cancer using PET/CT as a marker of response to therapies that don't involve chemotherapy. Patients were eligible for the study if they had stage 1 to 3a HER2-positive breast cancer with no prior therapy for breast cancer, and ultimately 356 patients were enrolled in a 1 to 4 randomization scheme with the majority of patients ultimately enrolled into the experimental group, which is called Group B. So, to break down Group A and Group B, Group A essentially were patients that receive typical standard of care, which at this point is TCHP for six cycles, neoadjuvantly or prior to surgery. Once they complete those cycles they move into surgery and then Herceptin-PERJETA adjuvantly for additional twelve cycles. I should also note that this study was conducted prior to results of the KATHERINE trial that showed benefit of switching to adjuvant T-DM1 if there's residual disease. So, patients in Group A as well as Group B did not receive T-DM1 at any point. So, again, Group A is kind of your standard of care. Group B was the “experimental arm.” And so, what they did in this arm to assess potential de-escalation strategies, patients first received Herceptin-PERJETA alone for two cycles with or without endocrine therapy, if they were also hormone receptor-positive. But after those two cycles, they underwent a PET/CT, and then if a response was garnered, they would continue with Herceptin-PERJETA and again plus or minus endocrine therapy to complete six cycles total before proceeding on with surgery. Then if they were fortunate enough to achieve complete response at the time of surgery, then they just continued with Herceptin-PERJETA maintenance, whereas if they did not achieve a complete response at the time of surgery, then they actually received TCHP 6 times adjuvantly. So, the chemotherapy was introduced after surgery. And then going back to that PET/CT time point, if patients did not achieve a response at that check-in point, after 2 cycles of Herceptin-PERJETA, at that point they were transitioned to chemotherapy with TCHP, again, for six cycles. So, either they could kind of ride all the way through if they got that complete response at the time of surgery with Herceptin-PERJETA only, or if at surgery there was residual disease, they went on to receive TCHP after surgery, or if they did not have a response on that interim PET/CT after 2 cycles of HP then they would go on to receive TCHP neoadjuvantly. So, looking at the results, they actually had 2 primary endpoints. The first primary endpoint was rates of a complete response at the time of surgery in patients that had a PET response. So, PET responses were actually seen in nearly 80% of all the patients treated with Herceptin-PERJETA without chemotherapy. And in those PET responders, a complete response rate at the time of surgery was seen in approximately 38% of patients. So, 37.9% of PET responders actually achieved a complete response when they went to surgery after receiving Herceptin-PERJETA alone, which is pretty amazing. I mean, we're used to seeing higher complete response rates with neoadjuvant therapy for HER2-positive disease, but again, this is a chemo-free regimen so that is encouraging for that 38% of patients that really didn't need chemotherapy. And then the second primary endpoint, and this was what we saw basically for the first time with the 2023 ASCO Meeting, was results for the 3-year invasive disease-free survival in Group B or this experimental de-escalation group. And ultimately it was shown that the three-year invasive disease-free survival and the intent to treat group B population was 95.4%, which met its statistical endpoint, or, basically the null hypothesis was rejected. They just needed some sort of outcome that was not worse in terms of the 3-year invasive disease-free survival of 89%. And then looking actually at the patients that kind of did the best. So, the patients that were PET responders and achieved a complete response at the time of surgery and therefore really only ever received Herceptin-PERJETA, their three-year invasive disease-free survival was 98.8%. So, really very good. Additional endpoints they looked at in Group A and Group B were favorable in terms of three-year invasive disease-free survival in Group A, and then three-year distant disease-free survival and three-year overall survival in both groups, all approximately 98%. So, very favorable. So, ultimately, these findings reflect a potential role for a chemotherapy-free treatment approach for some patients with early-stage HER2-positive breast cancer. And this particular study, they used PET/CT to influence chemotherapy decision-making, which potentially identified 1 in 3 patients who can omit chemotherapy. With that, 80% of patients receiving the response with a PET/CT, and then of that, 80%, again, 38% actually having that complete response. And ongoing work is also being done to look at other mechanisms to assess for an opportunity to de-escalate with MRI imaging or HER2DX testing to again try to identify patients who can potentially defer chemotherapy in this setting. I did not see from the results what proportion of patients were hormone receptor-positive, which I think is also interesting when thinking about chemotherapy de-escalation, can you lean a little bit more heavily on endocrine therapy? Perhaps we'll get that data in the future. Dr. Allison Zibelli: That's a very important point. I would like to thank you, Dr. Heeke, for coming on the podcast today and sharing your valuable insights with us. We really appreciate it. Dr. Arielle Heeke: Absolutely. It was a great meeting to dive into. It's always exciting to see what comes out of ASCO in the breast space. We're usually well represented there, and I hope that these studies will lead to further exploration. Dr. Allison Zibelli: And thank you to our listeners for joining us today. You'll find links to all 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. Follow today's speakers:  Dr. Allison Zibelli  Dr. Arielle Heeke @HeekeMD   Follow ASCO on social media:   @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn    Disclosures:   Dr. Allison Zibelli:   None Disclosed  Dr. Arielle Heeke: Honoraria: Merck Consulting or Advisory Role: Jazz Pharmaceuticals, Caris Life Sciences, Amgen, Daiichi Sankyo/Astra Zeneca, Pfizer, AstraZeneca, Menarini, Genome Insight Speakers' Bureau: Daiichi Sankyo/Astra Zeneca  

united states philadelphia speaker er north carolina staying patients consulting pfizer breast cancer hp gi drs advances mri astrazeneca pd cps immunotherapy asco group b amgen disclosures mbc torchlight her2 pfs atrium health pd l1 ihc pet ct jefferson health neutropenia ekgs asco annual meeting cdk4 ctdna qtc levine cancer institute menarini sidney kimmel cancer center t dm1 transcript dr tchp

HER2 Testing in Breast Cancer: ASCO-CAP Guideline Update

Play Episode Listen Later Jun 7, 2023 24:56

Dr. Antonio Wolff and Dr. Kim Allison discuss the latest ASCO-CAP guideline update on HER2 testing in breast cancer. This guideline update affirms previous recommendations, and provides commentary based on data from the DESTINY-Breast04 trial. Dr. Wolff and Dr. Allison review the questions from the oncology and pathology community raised by these results, and provide commentary on patients with HER2 IHC 1+ and 2+ and ISH-negative metastatic breast cancer. Read the guideline update, "Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: ASCO-CAP Guideline Update" at www.asco.org/breast-cancer-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/breast-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest disclosures in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.22.02864 Brittany Harvey: Hello and welcome to the ASCO Guidelines Podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I am interviewing Dr. Antonio Wolff from Johns Hopkins Sidney Kimmel Comprehensive Cancer Center and Dr. Kim Allison from Stanford University School of Medicine, co-chairs on ‘Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: ASCO-CAP Guideline Update'. Thank you for being here, Dr. Wolff and Dr. Allison. Dr. Antonio Wolff: Thank you. Dr. Kim Allison: Thanks for having us. Brittany Harvey: Then, before we discuss this guideline, I'd like to note that ASCO takes great care in developing its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the full guideline panel, including our guests on this episode today, are available online with the publication of the guideline and the Journal of Clinical Oncology, linked in the show notes. So now jumping into the content, to start us off, Dr. Wolff, what prompted the update expert panel to revisit the 2018 ASCO-CAP recommendations on HER2 testing and breast cancer, and what is the scope of this update? Dr. Antonio Wolff: Thank you, Brittany. We appreciate the opportunity of being with you today, and it's great to be here with my colleague, Dr. Kim Allison, as well. What triggered this informatory update was the release from data in trial DESTINY-Breast04, which tested the antibody-drug conjugate trastuzumab deruxtecan in patients who in the past would have been considered to have HER2-negative disease. This ADC, trastuzumab deruxtecan, has a topoisomerase inhibitor payload that is linked to the antibody trastuzumab. And in the past, from all the previous data we had, trastuzumab alone, or in combination with chemotherapy, or as part of another antibody-drug conjugate T-DM1 was essentially active in patients with HER2-positive disease, which is traditionally defined as having overexpression of the HER2 protein, which almost by default is a result of gene amplification of the HER2 gene. And what data from initial studies appear to suggest is that patients who would not be traditionally considered HER2-overexpressed or HER2-amplified were potentially benefiting or having evidence of clinical activity against this disease in the study of metastatic disease. And this was a randomized clinical trial for patients with metastatic breast cancer whose tumors were centrally determined to have IHC 1+ or IHC 2+ expression and would not have been called HER2-positive, would not have been called HER2-overexpressed. And for the tumors that were HER2 2+, they also had to have absence of gene amplification by an in-situ hybridization assay. And what was very interesting is that there was a meaningful, clinically significant improvement in survival for that patient population. And that has some clinicians to begin asking whether there is a different subset of patients who would have in the past been called as having HER2-negative disease that now could potentially be a candidate for this drug. And is there a difference between these patients and patients who, in the past, would have been called as HER2-negative on the basis of IHC 0? And so what complicated things for us a little bit is that patients with IHC 0 were not eligible for this trial. And what is left unanswered by this clinical trial is whether all patients who don't have HER2 protein overexpression or HER2 gene amplification would potentially have benefited from this drug. Kim? Dr. Kim Allison: Yeah, agree. I think the main impetus for the update was the exciting results from the DESTINY-Breast04 trial and the questions then that the pathology community and the oncology community had about whether this should change HER2 testing guidelines. Brittany Harvey: I appreciate that background on what prompted the panel to revisit this guideline. So then, Dr. Allison, how did the panel come to the conclusion that the previous recommendations are current and valid? Dr. Kim Allison: Right. So, as Antonio mentioned, the whole reason HER2 testing was first initiated was HER2-targeted therapies that showed response in the overexpressed or amplified tested population. And so guidelines have really been fine-tuned and crafted around distinguishing the HER2-positive for over-expression and amplification from negative. And this trial really questioned that in that maybe we can target lower levels of the HER2 protein, but this assay really wasn't designed for that. So we looked at the data from the trial and some of the limited other data that's out there and really came to the conclusion that, look, everyone in DESTINY-Breast04 benefited. The whole population benefited, whether you were 1+ or 2+. And because 0s were excluded from the trial, we don't know if they benefited. So we thought it was premature to create a new category, a new result category, and change our current reporting to a HER2-low category, mainly because we don't know that there's a new predictive threshold for response to treatment. So essentially, what we've got is a trial that showed great benefit but didn't create a new biomarker that is predictive or prognostic. Instead, it repurposed this older test as a trial entry criteria. And so now we're kind of stuck with 1+ or 2+ ISH negative as their trial entry criteria that gives you eligibility for trastuzumab deruxtecan. So essentially, we reaffirmed our prior recommendations with acknowledgment that what these categories: positive, equivocal, and negative, refer to is for protein overexpression or gene amplification and that we should continue to use the same scoring criteria, 1+, 2+, 0, and interpretation as were used in DESTINY-Breast04 for their clinical trial criteria. But awareness is important. Dr. Antonio Wolff: Yeah, the other thing that I would add, Brittany, I think we need to go back to what was the purpose of HER2 testing back in 1998 when we identified the survival benefit from trastuzumab in metastatic disease. And then, in 2005, when we had evidence of adjuvant benefit in improving disease-free and then overall survival for patients with early-stage disease. And the immunochemistry assays at that time were developed to differentiate between patients who had HER2 overexpressing disease or HER2 gene amplified disease versus not. At that moment, it was clearly identified that patients were considered as having HER2-positive disease that defined a biological entity, a tumor subtype, a group of patients who had worse prognoses in the absence of therapy. But then when they were treated with, for instance, chemotherapy with anthracyclines at that time, but then with HER2 targeted therapies with antibodies, these patients that otherwise would have a poor prognosis now were having an improved outcome. HER2 was a marker of poor prognosis but also a marker of a good chance of deriving clinical benefit, so there was a predictive benefit. And everything else, IHC 0, 1 or 2+, ISH-negative, there has been no evidence that targeting the HER2 pathway was clinically important. Or even more meaningful, there was no evidence that these patients have– within the subset of patients that don't have HER2 positive or overexpressing disease - there has been no evidence that those patients have a different outcome based on low levels of expression of HER2. A couple of years ago, in terms of trastuzumab, the NSABP reported findings in the data from NSABP B-47 where the antibody trastuzumab was added to chemotherapy to patients who were considered to have low levels of IHC expression, and in that case, was IHC 1+ or IHC 2+ gene non-amplified. And that settled the issue for sure, that there was absolutely no benefit in the adjuvant setting from the addition of trastuzumab. So we know that there's something different going on here. We know that if you now combine trastuzumab with a specific payload, in this case, the drug deruxtecan, which is a topoisomerase inhibitor, we are potentially targeting the HER2 protein. But these are tumors that are not considered HER2 addicted. These are not tumors whose biology is dependent on the HER2 pathway, so this is simply a better drug delivery. And in this sense, data and evidence from Michael Press, a pathologist at USC that has done some seminal work with HER2 and HER2 testing, he once proposed that the vast majority of breast cancers have some level of HER2 present. And a lot of what is considered IHC 0 is an artifact related to suppression of the detection of the HER2 protein. So there's a chance that the tumors that are truly HER2 negative or HER2 0 are going to be a very small proportion. And IHC assays were never optimized to measure very low levels of HER2. They just don't have the dynamic range for that. And then, from a clinical standpoint, there is no evidence that different levels of HER2 when, in the absence of overexpression, identify groups of patients that have disease that have a different biologic behavior. And I think, as Dr. Allison just mentioned, we don't have any evidence from the DESTINY-Breast04 trial that there is a differential benefit between IHC 1+ versus IHC 2+, ISH-negative. Those patients appear to equally benefit from therapy. Brittany Harvey: Understood. That context is helpful in understanding this updated guideline. So then you've both mentioned the category of patients who are HER2 IHC 1+ and 2+, and ISH-negative. So, Dr. Allison, this article includes a special commentary on those patients, those with HER2 IHC 1+ or 2+, and ISH-negative metastatic breast cancer. What are the essential points of this commentary? Dr. Kim Allison: Yeah. So some of them we've brought up already that this test for HER2 IHC wasn't really designed to detect the low levels of protein expression that may be present in some breast cancers, including the all-important issue that the IHC 0s may not be truly null for HER2, that we may just not be sensitive enough to detect it, or there may be fixation and ischemia, time issues that are very subtle and create a false negative result, essentially by IHC that, and that in addition to not being necessarily predictive or prognostic, the 0 versus 1+ threshold, which really is a threshold that hasn't been tested yet. But since eligibility for trastuzumab deruxtecan essentially now hinges around that 0 versus 1+ threshold, since these were clinical trial entry criteria, what can pathologists do to make best practice efforts to distinguish 0 from 1+? Because we felt like we should make some helpful recommendations, at least since this does appear to be a current status point that pathologists are going to be struggling with in practice. So the points we come up with in that commentary are to follow best practices, like making sure you're using the standardized ASCO-CAP Guidelines criteria. Making sure you pay attention to pre-analytic conditions of the tissue sample and that you're using controls with a range of protein expression, including 1+, to help ensure you've got an assay that's really looking at the right limit of detection since that has shifted somewhat in this instance. And then for interpretation side, for pathologists to be sure to look on high power, so discriminating at 40x when you're trying to score a 0 versus 1+ stain since that's now relevant, you're going to need to go on high power and really distinguish from those two. And then, consider a second pathologist review in borderline or challenging cases or perhaps using additional tools. There's some additional tools online. There are learning sets that are out there to help with that distinction. Dr. Antonio Wolff: What I would add to that is that I think, and Kim, I'm thinking of the pathologist now getting phone calls from oncologists saying, “Hey, Doctor Pathologist, you report this cancer as being IHC 0, and are you sure that this is truly IHC 0?” And I think we need to be careful not to put pathologists in an unfair situation. And I think we also need to be careful based on our behavior as oncologists that we could almost cause the extinction of the diagnosis of IHC 0 if pathologists feel somehow compelled to “try to help the oncologists” and potentially call a tumor that they would otherwise have called IHC 0, that they call that tumor IHC 1+. And I think the reason for being cautious, as Kim mentioned, is these assays were not optimized for the ability to truly distinguish between IHC 0 and 1+. And we do not know if tumors that are IHC 0 clinically behave differently from tumors IHC 1+. Right now, that does not appear to be the case. And I think to a degree, we are being forced, based on the decision by the study sponsors to launch a study that excluded patients of IHC 0. We are left, I often say, twisting ourselves into pretzels, trying to come up with a way to discriminate between IHC 0 and 1+ simply because of the eligibility of the clinical trial and now the resulting FDA label for the study. Because it is plausible that what if patients who had tumors that were IHC 0 had been included in this clinical trial? And what if we had determined that those patients also benefited from this new exciting antibody-drug conjugate? In that case, we would not be talking about creating new categories of HER2 low versus HER2 “ultra-low” and HER2 0, HER2 null. Because essentially, we would have identified a new clinical use for this exciting antibody-drug conjugate for patients who have tumors that are HER2 not overexpressed and HER2 not amplified. So, in fact, it is entirely plausible that the population of patients that could benefit from this antibody may go well above the original intent of DESTINY-Breast04. We just don't have the evidence at this point to say that those patients who would be called IHC 0 don't benefit. It's just that they were not included in the clinical trial. Brittany Harvey: Well, your points there from both of you lead nicely into my next question, in that you've talked a little bit about how this impacts both oncologists and pathologists. So, Dr. Wolff, what does this guideline and commentary mean for both clinicians and patients with breast cancer? Dr. Antonio Wolff: So I think what I would try to reassure oncologists, pathologists, and also patients and their caregivers and loved ones, over the last 20 years, I think we have seen a meaningful improvement in the quality of HER2 testing. And I think pathologists and oncologists recognize that breast cancer biomarkers, in general, in the past, were used purely for prognostic reasons or to complement anatomic pathology from a diagnostic standpoint. But now, many of these assays, especially ER and HER2, are used as the sole determinant of therapy selection in a binary fashion. If you are positive for ER, you can be a candidate for ER-targeted therapy. If you're positive for HER2, you may be a candidate for HER2-targeted therapy. And I think even though the current generation of IHCs were not equipped to make a differentiation between very low levels of HER2 expression from potentially no levels of HER2 expression, with all the limitations we just said, I think pathologists are today doing a very good job. They understand the importance of the work they do in helping us clinicians take care of patients in the clinic. As I often joke, pathologists are wearing the stethoscope with us. So I think we need to be kind to pathologists and not put them under the microscope, if you will, pun intended, or putting a lot of pressure on them. And I think I tend to trust the quality of the work they do. I think there are two things that I would like to see happening. Number one, I would love to see the study sponsor allowing investigators to use a new generation of assays that are more quantitative to be able to back on DESTINY-Breast04 and test specimens of the patients that were triggered on the trial and see if there is a differential benefit in the observed outcomes of patients treated with trastuzumab deruxtecan according to levels of HER2, but that can be measured using a truly quantitative assay. And there are a lot of new assays out there. And I think the sponsors, they do have an obligation to all the patients who are participating in the trial to allow those things to happen. And the second piece is obviously to develop assays that are more quantitative than a traditional IHC. And Kim, along these lines, a question that often comes up is what to do with patients who may have had a previous test that was IHC 0. And what should we, I guess, recommend to clinicians that they do with this situation? Dr. Kim Allison: Yeah, I think this is a common question, and because of the unreliability of a 0 versus 1+ result, and we do see them change when you look at metastatic, or core versus primary surgical excision, 0 versus 1+ results shift around much more so than you'd expect if this was a true biologic difference. So I would look at a spectrum of samples across the metastatic progression. So if any of them are not 0, I think that's a result worth looking at. And considering that either there's heterogeneity there potentially or the 0s were false negatives and not consistent over time, so I would test the metastatic sample again. If you have a new sample, if that's 0, I would still consider treating based on a prior 1+ result or a different sample that's metastatic. Dr. Antonio Wolff: Yeah, the one thing that I haven't done yet is actually for patients who have had– Let's say, that I have a primary term that was IHC 0, and then, they had, unfortunately, metastatic disease, and the diagnostic tissue that confirmed that they had metastatic disease also tested IHC 0. And now they are– unfortunately, disease has progressed after first or second-line therapy, be it anti-estrogen if they had ER-positive disease or chemotherapy if they had ER-negative disease. What I have not done is to request a new biopsy exclusively for the purpose of doing another HER2 test because in case the tumor had changed expression from 0 to 1+. Because what we don't know because of the variability, etc., Dr. Allison was just describing whether that change is real or not. Again, it's really unfortunate that patients who were IHC 0 were not allowed for this study. There are other studies taking place right now looking at tumors that are more than IHC 0 and less than IHC 1+; that's DESTINY-Breast06. And those patients are being called by the study sponsor as “ultra-low”. Although I am not a pathologist, but I have no idea how a pathologist can truly try using immunohistochemistry today; really reliably differentiate between it's not 0, it's not 1+, it's in between. I am just concerned that I think we may be asking or putting pathologists in a hard spot, asking them to do something with an assay that was not designed to perform that way. Dr. Kim Allison: Even if we could get the interpretation perfect, to have digital tools to help us with interpretation, I think at that low level, IHC is just really sensitive to pre-analytics and analytic factors that are subtle. Even having a slide that's been sitting unstained for a week or so might change a 1+ to a 0 result. So it really is sensitive, maybe too sensitive, to those kinds of factors. Brittany Harvey: Absolutely. Well, thank you both for those insights on what's facing clinicians and patients and the commonly asked questions today. So then we've spent a lot of time talking about what's happened recently in this field. But, Dr. Allison, what are the ongoing developments and outstanding questions you're all facing regarding HER2 testing and breast cancer? Dr. Kim Allison: Yeah. I mean, I think we've covered some of those. Is IHC 0 truly 0? Would it be responsive to T-DXd or other antibody-drug conjugates targeting HER2? And so if that is relevant, then there's a lot of work looking at maybe more sensitive or quantitative assays that are really designed to detect those lower levels of expression, unlike the current assays. And then digital image analysis to standardize interpretation if they are leading to differences. And then new standards to help us calibrate. Brittany Harvey: Great. Well, I want to thank you both so much for all of your work to review and update this guideline on HER2 testing in breast cancer. And thank you for your time today, Dr. Wolff and Dr. Allison. Dr. Kim Allison: Thanks for having us. Dr. Antonio Wolff: Our pleasure. It's fun. Thank you. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline update, go to www.asco.org/breast-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe, so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

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Lo mejor de SABCS 2022

ScienceLink

Play Episode Listen Later Jan 5, 2023 25:26

El Dr. Efraín Salas, oncólogo médico adscrito al Centro Médico Nacional de Occidente, IMSS en Guadalajara, Jalisco, México, nos habla sobre los estudios más relevantes presentados durante el Simposio de Cáncer de mama de San Antonio 2022 (SABCS, por sus siglas en inglés). Cáncer de mama en estadio temprano: monarchE: Estudio fase III, aleatorizado y abierto, que evaluó abemaciclib combinado con terapia endocrina adyuvante estándar vs. terapia endocrina adyuvante estándar sola en pacientes con cáncer de mama de alto riesgo, ganglios positivos, en estadio temprano, RH+/HER2-. Los datos actualizados se enfocaron en el análisis de supervivencia global provisional, así como en la supervivencia libre de enfermedad invasiva y la supervivencia libre de recaída a distancia. POSITIVE: Estudio internacional, prospectivo y de un solo brazo, que evaluó los resultados del embarazo y la seguridad de interrumpir la terapia endocrina para mujeres jóvenes con cáncer de mama sensible al sistema endocrino que desean quedar embarazadas. Cáncer de mama avanzado RH+: EMERALD: Estudio fase III, aleatorizado, multicéntrico, abierto y controlado con tratamiento activo, que evaluó elacestrant como monoterapia vs. el estándar de atención para el tratamiento de pacientes con cáncer de mama avanzado RE+/HER2- después del tratamiento con un iCDK4/6. RIGHT Choice: Estudio fase II, aleatorizado, multicéntrico y abierto, que evaluó la combinación de ribociclib + acetato de goserelina con terapia hormonal vs. la quimioterapia (QT) de elección médica (docetaxel/capecitabina o paclitaxel/gemcitabina o capecitabina/vinorelbina), en pacientes premenopáusicas o perimenopáusicas con cáncer de mama localmente avanzado o metastásico inoperable con RH+/HER2-. TROPiCS-02: Estudio fase III, aleatorizado, multicéntrico y abierto, que evaluó sacituzumab govitecán (IMMU-132) vs. el tratamiento de elección del médico, en pacientes con cáncer de mama metastásico RH+/HER2- que hayan fracasado al menos a dos regímenes de QT previos. Cáncer de mama HER2+: DESTINY-Breast02: Estudio fase III, aleatorizado, multicéntrico, abierto y controlado, que evaluó trastuzumab deruxtecan (DS-8201a) vs. el tratamiento elegido por el investigador para pacientes con cáncer de mama HER2+, irresecable y/o metastásico previamente tratadas con trastuzumab emtansina (T-DM1). DESTINY-Breast03: Estudio fase III, aleatorizado, multicéntrico, abierto y controlado, que evaluó trastuzumab deruxtecan (DS-8201a) vs. trastuzumab emtansina (T-DM1) para pacientes con cáncer de mama HER2+, irresecable y/o metastásico previamente tratadas con trastuzumab y QT con taxanos. Videograbado: 4 de diciembre de 2023 Todos los comentarios emitidos por los participantes son a título personal y no reflejan la opinión de ScienceLink u otros. Se deberá revisar las indicaciones aprobadas en el país para cada uno de los tratamientos y medicamentos comentados. Las opiniones vertidas en este programa son responsabilidad de los participantes o entrevistados, ScienceLink las ha incluido con fines educativos. Este material está dirigido a profesionales de la salud exclusivamente.

san antonio nacional lo mejor ds estudio guadalajara salas jalisco occidente qt tropics efra imss her2 centro m simposio immu t dm1

Enhertu Offers Better Overall Survival Than Kadcyla for Metastatic HER2-Positive Breast Cancer

Breastcancer.org Podcast

Play Episode Listen Later Dec 9, 2022 8:59

2021 results from the DESTINY-Breast03 study showed that Enhertu (chemical name: fam-trastuzumab-deruxtecan-nxki) more than doubled the 12-month progression-free survival rate compared to Kadcyla (chemical name: T-DM1 or ado-trastuzumab emtansine) in people diagnosed with metastatic HER2-positive breast cancer that had been previously treated. At the 2022 San Antonio Breast Cancer Symposium, Dr. Sara Hurvitz presented new overall survival results, showing that Enhertu also improves overall survival compared to Kadcyla. Listen to the episode to hear Dr. Hurvitz explain: overall survival and progression-free survival results severe side effects of Enhertu how the researchers managed any severe lung problems that developed in people receiving Enhertu

positive survival offers breast cancer metastatic her2 san antonio breast cancer symposium enhertu sara hurvitz t dm1 kadcyla

TILs, Olutasidenib, T-DXd

OncoPharm

Play Episode Listen Later Dec 8, 2022 17:52

Tumor-Infiltrating Lymphocytes (TILs) getting closer to entering practice. Updated survival results published from DESTINY-Breast03 (T-DXd vs. T-DM1). A new IDH1 inhibitor, olutasidenib, is FDA-approved for relapsed or refractory AML.

fda aml tils idh1 t dm1

Breast Cancer | Meet The Professor: Optimizing the Management of HER2-Positive Breast Cancer — Part 2

Play Episode Listen Later Oct 21, 2022 63:36

Featuring perspectives from Dr Nancy Lin, including the following topics: Introduction: Journal Club with Nancy U Lin, MD (0:00) Case: A woman in her late 60s with ER-positive, HER2-positive breast cancer who has significant neuropathy and develops liver metastases after adjuvant docetaxel/carboplatin/trastuzumab — Laurie Matt-Amaral, MD, MPH (15:30) Case: A woman in her late 80s with weakly ER-positive, PR-negative, HER2-positive, gBRCA2 mutation-positive T2N1M0 breast cancer after neoadjuvant paclitaxel/trastuzumab — Zanetta S Lamar, MD (20:16) Case: A woman in her early 50s with ER/PR-negative, HER2-positive metastatic breast cancer (mBC) with progressive brain metastases after T-DM1 and whole braid radiation therapy — Justin Peter Favaro, MD, PhD (31:06) Case: A woman in her late 40s with triple-positive breast cancer after resection of brain metastasis — Shaachi Gupta, MD, MPH (37:26) Case: A woman in her mid 60s with ER/PR-positive, HER2-low mBC after endocrine therapy-based treatments, capecitabine — Vignesh Narayanan, MD (46:44) Case: A woman in her early 60s with progressive triple-positive mBC receiving T-DXd — Joseph Martins, MD (54:36) CME information and select publications

pr phd professor management er positive md optimizing breast cancer mph cme mbc her2 t dm1

Breast Cancer | Oncology Today with Dr Neil Love: Recent Updates in the Management of HER2-Low Breast Cancer

Play Episode Listen Later Aug 2, 2022 24:58

Efficacy data with T-DXd from the DESTINY-Breast04 trial for patients with HER2-low breast cancer; incidence and biologic relevance of HER2 mutations in breast cancer (0:00) Current and potential clinical roles for liquid biopsy in breast cancer; cardiac toxicity with T-DXd in the DESTINY-Breast04 trial (6:10) Safety profile of T-DXd from the DESTINY-Breast04 trial (11:09) Incidence and management of interstitial lung disease caused by T-DXd (14:54) Disease- and patient-specific factors and other considerations in the sequencing of chemotherapy, antibody-drug conjugates, tyrosine kinase inhibitors, SERDs (selective estrogen receptor degraders) and CDK4/6 inhibitors for breast cancer (21:45) Case: A woman in her early 60s with new lobular Stage II breast cancer 20 years after previous breast cancer on the same side (28:39) Case: A woman in her late 20s with a right breast lump and a strong family history of breast cancer (36:12) Case: A woman in her late 30s presenting with right axillary pain who experiences disease progression on T-DM1 and then receives T-DXd (46:09) Future of novel antibody-drug conjugates alone and in combination with immunotherapy for breast cancer (52:35) CME information and select publications

future management safety current disease breast cancer oncology efficacy cme incidence her2 stage ii cdk4 neil love t dxd t dm1 serds

DESTINY-Breast04 and Other Key Breast Cancer Studies at ASCO22

Play Episode Listen Later Jun 21, 2022 31:01

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

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Systemic Therapy for Advanced HER2-Positive Breast Cancer Guideline Update

Play Episode Listen Later May 31, 2022 13:34

An interview with Dr. Sharon Giordano from the University of Texas MD Anderson Cancer Center in Houston, TX, and Dr. Nancy Davidson from Fred Hutchinson Cancer Research Center and the University of Washington in Seattle, WA, co-chairs on "Systemic Therapy for Advanced HER2-Positive Breast Cancer: ASCO Guideline Update." This guideline updates recommendations on systemic therapies for advanced HER2-positive breast cancer, focusing on second-line, third-line, and greater treatment. Read the full guideline. TRANSCRIPT Brittany Harvey: Hello and welcome to the ASCO Guidelines Podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one at asco.org/podcasts. My name is Brittany Harvey and today I'm interviewing Dr. Sharon Giordano from the University of Texas MD Anderson Cancer Center in Houston, Texas, and Dr. Nancy Davidson from Fred Hutchinson Cancer Research Center and the University of Washington in Seattle, Washington, co-chairs on 'Systemic Therapy for Advanced Human Epidermal Growth Factor Receptor 2 Positive Breast Cancer: ASCO Guideline Update'. Thank you for being here. Dr. Giordano and Dr. Davidson. Dr. Sharon Giordano: Thank you. Dr. Nancy Davidson: Thank you for having us. Brittany Harvey: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Giordano, do you have any relevant disclosures that are directly related to this guideline topic? Dr. Sharon Giordano: No, I do not. Brittany Harvey: Thank you. And Dr. Davidson, do you have any relevant disclosures that are directly related to this guideline topic? Dr. Nancy Davidson: No, I do not. Brittany Harvey: Thank you. Let's talk about the content of this guideline update. So first, Dr. Giordano, what prompted an update to this guideline on the systemic therapy for advanced HER2-positive breast cancer, and what is the focus of this update? Dr. Sharon Giordano: So, we were prompted to update the guidelines for HER2-positive metastatic breast cancer because several new studies have been presented and published, which are really changing our standard of care approaches. We have new therapies and new combinations that have resulted in improvements in progression-free survival and in overall survival for this patient population. Given the clinical importance of these new studies, we felt that an update of the treatment guidelines was clearly needed. Overall, the focus of our update is really in the title, so, it's systemic therapies for advanced HER2-positive breast cancer. And specifically, what we're focusing on is updating the recommendation for second-line therapy, and then adding multiple new options for systemic therapies for third-line and greater treatment. Brittany Harvey: Great. Thank you for that overview. So, then I'd like to review the updated recommendations of this guideline for our listeners. Starting with, Dr. Davidson, what is recommended for first-line therapy for patients with advanced HER2-positive breast cancer? Dr. Nancy Davidson: So, that was the part of this guideline that really did not change. In the previous iteration and in the current iteration, we felt that the evidence suggested that a combination of trastuzumab and a taxane should be the first-line treatment for individuals with metastatic HER2-positive breast cancer unless they have some sort of contraindication to the taxanes. Now, the evidence supporting that is very strong. The trial that supported this continues to be updated and continues to show benefit. So, that's a very high level of evidence and our recommendation on this was extremely strong. Brittany Harvey: Great. And then following those first-line recommendations, Dr. Giordano, what is recommended for second-line treatment for these patients? Dr. Sharon Giordano: So, we did change our recommendation for second-line treatment for HER2-positive patients. The current new recommendation is, and I quote from our guideline, “If a patient's HER2-positive, advanced breast cancer has progressed during or after first-line HER2 targeted therapy, and the patient has not received trastuzumab deruxtecan, clinicians should recommend trastuzumab deruxtecan as a second-line treatment.” So, as I said before, this recommendation is a change from our prior second-line recommendation. Previously, we had recommended T-DM1. So, this change was really, I think, one of the most important changes to the guidelines with this update. We made the recommendation based on the initial presentation of the results of the Destiny-Breast03 trial, really given the magnitude of the benefit that was seen in the study. And the manuscript I would note was published this month in the New England Journal of Medicine. Overall, the study showed statistically significant and highly clinically meaningful reduction in progression-free survival. So, just to give you some of these numbers, to kind of give you a sense of how big the impact was, so 76% of patients who were treated with trastuzumab deruxtecan versus 34% of patients treated with trastuzumab emtansine were alive and without disease progression at a year, with a hazard ratio of 0.28. The response rates are also quite impressive with 80% versus 34% response rates. And the overall survival data are still immature but do favor treatment with trastuzumab deruxtecan and that hazard was 0.55. So, I will note though, that toxicity was a bit higher with the new drug, with trastuzumab deruxtecan. So, any grade adverse events were 98% versus 87%. And then if you look at grade three and four drug-related adverse events, it was 45% versus 40%. I think of note, rather than just kind of the overall numbers, though, one thing that clinicians need to be aware of is the risk of interstitial lung disease with this new drug. And this occurred in about 10% of treated patients in this study, although only 1%, or I think it was two patients, who had grade three or higher pulmonary toxicity. So, this is a toxicity that is specific to this drug that clinicians do need to be aware of. Dr. Nancy Davidson: I think the other thing on that, Sharon, is that the incidence was lower in the Destiny Breast03 trial than it had been in some of the really early studies of this agent, so, that should be reassuring to us. Although, of course, it doesn't mean that the side effect doesn't happen, you have to take note of it. Dr. Sharon Giordano: That's a great point. It definitely was lower than we'd seen before. So, a little bit of a relief, but still there. Brittany Harvey: Great, thank you both for reviewing that data. I appreciate the overview. So then, following those recommendations for second-line treatment, Dr. Davidson, what are the recommended options for third-line therapy for patients with HER2-positive advanced breast cancer that has progressed on second-line or greater HER2 targeted therapy? Dr. Nancy Davidson: Well, of course, this is the area where there has been considerable change as well. And that's because of the wealth of new anti-HER2 agents that Dr. Giordano talked about earlier. So, we had a variety of recommendations for clinicians and patients to make decisions about how to proceed. I think certainly one of them, is that if the patient did not receive trastuzumab emtansine (T-DM1) in the second line, as we just talked about, our new recommendation would be that they would not, that they would receive trastuzumab deruxtecan, so you put off for T-DM1 in that [third-line] setting. And that's a new recommendation for us. And the strength of the recommendation is quite high. Another agent that's come along that's very exciting is tucatinib, one of the small molecule inhibitors. And we think that that is also an alternative, that tucatinib in combination with trastuzumab and capecitabine, again, nice activity and pretty strong recommendation based on analyzed critical trials. And then finally, if for some reason the patient didn't receive the trastuzumab deruxtecan in a second-line setting and you're now in the third-line setting, that would be a very reasonable agent for them as well. Those are all pretty strong recommendations. And I think the choice of which to proceed will depend a little bit on the decision making between the patient and the doctor about the mode of administration, your side effect profile, what seems the most appropriate, and it might be more one of the order of the recommendation. As opposed to saying, 'This one, but not that one', it might be, 'Pick this one next and know that you will be able to return to some of these in the future.' Now, there are a lot of other possibilities here. We already had available to us neratinib and capecitabine, that continues to be part of the portfolio. And we also had lapatinib and capecitabine, also part of the portfolio. Other combinations of chemotherapy, trastuzumab could be considered, a new agent called margetuximab with chemotherapy, which has also come on to the market. And of course, there's the possibility of thinking about the anti-HER2 agents in the context of endocrine therapy for those patients who have estrogen receptor-positive breast cancer as well. And new information suggesting that you might, in some cases, even think about one with CDK 4/6 inhibitors in the context of trastuzumab and fulvestrant. So, lots of possibilities here that patients and doctors can weigh, and again think about order of administration as opposed to selecting for or against the other. I do think that the leading contenders at the beginning are going to be T-DM1 or trastuzumab deruxtecan, if that hasn't been used, or tucatinib in combination, those would be my personal preferences. Brittany Harvey: Great. Thank you for reviewing those options and describing where a patient might receive these during their treatment. Dr. Nancy Davidson: I'd like to hear Dr. Giordano's thoughts on that, how would you stack those up? Dr. Sharon Giordano: Yeah, well, as you said, I think it does depend on what the patient's been treated with previously. I mean, certainly, T-DM1 or trastuzumab deruxtecan, if they haven't had those agents. Otherwise, I think the data from the tucatinib trastuzumab capecitabine regimen is pretty impressive as it did show an overall survival benefit. And as you know, I think that regimen is also really interesting, because it does seem to have some efficacy for patients with brain metastases. That actually has a very nice advantage. Then the other ones, I think it just sort of depends on what they've seen previously, what side effects they may be experiencing, and kind of other quality of life issues. I don't see that there's a clear way to sequence the other ones since most of them haven't really been directly compared head-to-head against each other. Brittany Harvey: It seems like it may be an individual discussion between clinicians and patients at that level. So, then, Dr. Giordano following that, how will this guideline impact clinicians and what should they know as they implement these updated recommendations? Dr. Sharon Giordano: I think the bottom line is really the clinicians are now going to have more options for the treatment of HER2-positive advanced breast cancer which is fantastic news to have all these different choices and options for our patients. To me, I think probably the most important changes and recommendations, again, are the addition of trastuzumab deruxtecan in the second-line setting just given the very impressive clinical benefit that's seen with that drug, or, as Nancy mentioned in the third-line setting if patients, for some reason haven't received it previously. And then I also think, as we talked about, the tucatinib combination is really an exciting new combination that does seem to have significant clinical benefit. I think the clinicians will need to be aware that that might be an option for patients with CNS metastases that are progressing. And also, just to be aware, as we mentioned before, about the risk of the interstitial lung disease with trastuzumab deruxtecan but it's really encouraging to me to have such a long list of drugs and combinations that we can use to treat our patients. Brittany Harvey: Excellent. Those are great points. So, then finally, to wrap us up, Dr. Davidson, in your view, how will these guideline recommendations impact patients with advanced HER2-positive breast cancer? Dr. Nancy Davidson: Well, Brittany, I think one thing we hope, of course, is that those patients will cumulatively have a longer survival, and a better survival as a consequence of all of these new insights that we've been able to make. I can imagine it would be maybe a little confusing to patients that there are so many things that they might potentially be able to choose from, but this is one where I think that the larger the panel of agents that you have available to you, the happier it is. So, I hope that patients are going to look at this as an opportunity for partnership with their oncologists to try to figure out of all these possibilities, what's the best one for me now, and they're going to have the comfort of knowing that there'll be other things that they can fall back on in the future, and that, hopefully, these things will improve outcomes. And again, without excessive toxicity. This last thing I'm going to hope that clinicians and physicians will remember is that we've made a lot of headway here, but that our results are not perfect. And so, right now, we're able to change guidelines, these guidelines today because of clinical trials that have been put together in the last several years and successfully implemented. And I hope that we're going to continue to do that because until we get to a point where survival from HER2-positive breast cancer is 100%, we've got work to do. So, they're going to be other new clinical research strategies, and I hope that doctors and patients will take advantage of those whenever possible. Brittany Harvey: Absolutely, both hoping for longer survival and better quality of life and looking forward to more clinical trials to give clearer answers. I want to thank you both so much for your time today and for all of your work on updating these guideline recommendations, Dr. Davidson and Dr. Giordano. Dr. Nancy Davidson: Thanks, Brittany. Dr. Sharon Giordano: Thank you so much. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guideline Podcast Series. To read the full guideline go to www.asco.org/breast-cancer-guidelines. There's a companion guideline update on the management of advanced HER2-positive breast cancer and brain metastases also just published in the Journal of Clinical Oncology and on asco.org. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines App available in iTunes or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast expressed 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.

university texas starting washington seattle medicine positive journal tx wa guidelines breast cancer davidson google play store cns new england journal giordano asco her2 clinical oncology cdk texas md anderson cancer center fred hutchinson cancer research center systemic therapy t dm1 asco podcast network asco guidelines podcast

Management of Advanced HER2-Positive Breast Cancer and Brain Metastases Guideline Update

Behind The Knife: The Surgery Podcast

Play Episode Listen Later May 31, 2022 14:18

An interview with Dr. Naren Ramakrishna from Orlando Health Cancer Institute in Orlando, FL, and Dr. Carey Anders from Duke University in Durham, NC, co-chairs on "Management of Advanced Human Epidermal Growth Factor Receptor 2 Positive Breast Cancer and Brain Metastases: ASCO Guideline Update." This guideline reviews evidence in both the local therapy management and systemic therapy management for patients with HER2-positive breast cancer and brain metastasis, and provides updated recommendations for these patients. Read the full guideline at www.asco.org/breast-cancer-guidelines. TRANSCRIPT Brittany Harvey: Hello and welcome to the ASCO Guidelines Podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows including this one at asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Naren Ramakrishna from Orlando Health Cancer Institute in Orlando, Florida. And Dr. Carey Anders from Duke University in Durham, North Carolina, co-chairs on 'Management of Advanced Human Epidermal Growth Factor Receptor 2 Positive Breast Cancer and Brain Metastases: ASCO Guideline Update'. Thank you for being here. Dr. Ramakrishna and Dr. Anders. Dr. Carey Anders: Thank you. Dr. Naren Ramakrishna: Thank you. Brittany Harvey: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Ramakrishna, do you have any relevant disclosures that are directly related to this guideline topic? Dr. Naren Ramakrishna: No. Brittany Harvey: And Dr. Anders, do you have any relevant disclosures that are directly related to this guideline topic? Dr. Carey Anders: I do. I would just like to disclose that I receive research funding, compensated consulting roles, and royalties from several of our industry partners who are developing brain permeable compounds. Brittany Harvey: Thank you. Let's talk about the content of this guideline. So, Dr. Anders, what prompted an update to this guideline? And what is the scope of this guideline update? Dr. Carey Anders: Thank you for that question, Brittany. Our previous guideline in the management of HER2-positive breast cancer brain metastasis was published in 2018. And since that time, we've seen significant progress in both the local therapy management and systemic therapy management for our patients with HER2-positive breast cancer and brain metastasis. I think collectively, this body of work really prompted the panel to think through the changes that we could make to improve the care of our patients taking these updates into account. I'd love to hear Dr. Ramakrishna's take on the rationale for the update as he was also involved in the 2018 guideline. Dr. Naren Ramakrishna: Thank you, Carey. Well, it's really an exciting time right now for breast cancer brain metastasis treatment. And the recent data that Dr. Anders referred to has really opened up a whole new era in terms of therapeutic possibilities for breast cancer brain metastasis patients. In the past, we've relied on traditional methods of treatment like whole-brain radiotherapy, surgery, and stereotactic radiosurgery as mainstays of treatment. But this exciting data that Dr. Anders referred to, has resulted in the possibility of avoiding certain of the local therapy options in select patients, which has the potential to increase patient survival and quality of life, and is a major advancement. Brittany Harvey: Excellent. It's great to hear about those advancements. So, then next, I'd like to start by reviewing the guideline recommendations for our listeners. Dr. Ramakrishna, what are the key recommendations for local therapy for patients with HER2-positive breast cancer and brain metastases? Dr. Naren Ramakrishna: Since the 2018 updated guidelines, we've continued with our stratification of patients by prognosis by the number of metastases, size of metastases, and also whether they are symptomatic or asymptomatic. Overall, the changes include the offering of systemic therapy for patients after multidisciplinary review for asymptomatic metastases, particularly those less than two centimeters in size. In select cases, one might also offer it for patients with metastases larger than that. The other major change that we see in this update is an increasing reliance on stereotactic radiosurgery rather than whole-brain treatment as a local therapy option, both in the post-operative setting and for single or multiple metastases, for which surgery is not recommended. Finally, we see a significant change in the application of whole brain radiation, where whole-brain radiation is recommended typically for extensive disease, either with multiple, very large metastases, or many, many small metastases. We recommend whole brain treatment to always be administered with a neuroprotectant, and where possible, with what's called hippocampal sparing, which is thought to reduce the neurocognitive negative effects of whole-brain radiation treatment. Brittany Harvey: Understood, I appreciate those recommendations for local therapy and that overview that you provided. So then Dr. Anders, in addition to those recommendations, what are the key recommendations for systemic therapy for these patients? Dr. Carey Andres: Sure, Brittany, happy to review. I think some of the general principles from the 2018 guidelines remain in place. So, for instance, our patients who have progressive disease in the brain, are eligible for local therapy and have controlled extracranial disease, we still recommend continuing the current HER2-directed therapy along with the same algorithm for the treatment of patients with HER2-positive metastatic breast cancer. There are some interesting and exciting changes to the guidelines with the advent of several of the promising systemic therapies that Dr. Ramakrishna outlines such that we do have the option of leading with systemic therapy for our patients with small asymptomatic lesions in the brain predominantly based on the HER2CLIMB clinical trial which established tucatinib, capecitabine and trastuzumab in this setting. So, in concert with our local therapist, we have the consideration for moving to the HER2CLIMB regimen in the setting of active asymptomatic brain metastasis in concert with our local therapist. So, that's one key change from the 2018 guidelines. Another is the introduction of the compound trastuzumab deruxtecan, an antibody-drug conjugate, which has been shown in second line in the setting of metastatic HER2-positive breast cancer to be superior to our traditional T-DM1 therapy in this setting. In the study, the Destiny-Breast03 study that illustrated the superiority of trastuzumab deruxtecan patients with stable brain metastasis were included and illustrated in this compound, illustrated significant benefit for patients with stable brain metastasis. So, in addition to the HER2CLIMB regimen in the setting of stable brain metastasis, we also have the option of trastuzumab deruxtecan in this setting. And that was an update in our 2022 guidelines. So, we essentially have more systemic therapy tools in our toolkit to consider in concert with local therapy. And I just want to emphasize the importance of communication between the systemic therapy team and the local therapy teams, particularly when we're making the decision to move forward with the systemic therapy in the setting of progressive or stable brain metastasis. Brittany Harvey: Thank you. Yes, that multidisciplinary care is key, and I appreciate your reviewing those updates. So then, in addition to those what is recommended regarding screening for the development of brain metastases for patients with HER2-positive breast cancer? Dr. Carey Andres: So, this is a very active conversation. And in fact, I had this very conversation with two patients in the clinic just yesterday. So, should we be screening our patients with advanced HER2-positive breast cancer with brain MRIs in the absence of symptoms? I think the bottom line is we just don't have the data yet. I think we will have the data and in fact, there are ongoing prospective studies trying to determine whether or not screening brain MRIs in the absence of symptoms in this setting will improve our patient survival, and also improve our patients' quality of life. Until we have that data because we do have these new tools in the toolkit for systemic therapy treatment, the panel loosens the guidelines a bit to say that it's not that we no longer recommend screening in the asymptomatic state, but there's not enough data for or against. And I think this really will help the physician and patients as they're making decisions about their screening and restaging studies in a personalized manner. In addition to the lack of data, we also strongly recommend that clinicians and patients have a very low threshold to obtain a brain MRI in the presence of symptoms and this is really important with regards to communication about symptoms as subtle as they may be. I'd love to hear Dr. Ramakrishna's take on this challenging space where we clearly need more data. Dr. Naren Ramakrishna: Yes, Carey, I completely agree that it's quite challenging and the practice patterns are quite diverse throughout the country. It's also a source of a great deal of apprehension and anxiety for patients who automatically typically would assume that more frequent screening is better, especially when they do develop brain metastasis if that's to occur. So, we do look forward to better data for guidance. And it certainly is an area that should undergo multidisciplinary reviewing recommendations for any particular patient. Brittany Harvey: Understood, thank you both for reviewing the evidence as it states now and we'll look forward to that emerging data for perhaps a future guideline update. So then, Dr. Ramakrishna, what in your view is the importance of this guideline update and what does it mean for clinicians? Dr. Naren Ramakrishna: Well, this is a practice-changing update. I mean, I don't think that's an overstatement. Because for the first time, upfront therapy is going to include the possibility of systemic therapy. And this also means that there has to be multidisciplinary and multimodality discussions regarding local versus systemic therapy for a large proportion of HER2-positive breast cancer brain metastasis patients. So, practice patterns are going to shift as a result of the incorporation of systemic therapy into the treatment paradigm. And finally, the other very important, practice-changing local therapy change is that the use of whole-brain treatment will be reduced relative to stereotactic radiosurgery, but in some cases, also as a result of the use of systemic therapy, and when it is employed, it must be utilized with a neuroprotectant and/or hippocampal sparing. Brittany Harvey: Great and then finally, how will these guideline recommendations affect patients with HER2-positive metastatic breast cancer and brain metastases? Dr. Carey Andres: So, I would just echo Dr. Ramakrishna's comments about the advances that we've seen and the importance of multidisciplinary care. I think from a systemic therapy perspective, we have the wonderful problem of having multiple agents to consider in this space. And as we've seen, really an explosion of HER2-directed therapies that are now approved and available to patients. One of our challenges has been how to sequence these therapies. And so, we were hopeful that these guidelines will help clinicians and patients determine when to pick individual regimens that best fit the patient's scenario, whether or not their brain metastases are stable at that decision tree, or whether or not they're progressive at that decision tree. I would also point the listeners to the updated guidelines in the management of patients with HER2-positive metastatic breast cancer, as these guidelines will certainly complement the decision-making and systemic therapy, incorporating the presence or absence of brain metastasis. Brittany Harvey: Great, and yes, thank you for highlighting that companion guideline. Both are available at asco.org/breast-cancer-guidelines and in the Journal of Clinical Oncology. So, I want to thank you both so much for your work on these guidelines and for taking the time to speak with me today, Dr. Anders and Dr. Ramakrishna. Dr. Naren Ramakrishna: Thank you very much, Brittany. Dr. Carey Andres: Thank you! Thanks for the opportunity. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast series. To read the full guideline go to www.asco.org/breast-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines App available in iTunes or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.

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Season 2 Game 19: Jeroen Debaveye

The Huddle by Tip-Off

Play Episode Listen Later Jan 9, 2022 68:49

game als heb jeroen volgende vlaanderen communicatie t dm1

Top Research Presented at the 2021 San Antonio Breast Cancer Symposium

Breastcancer.org Podcast

Play Episode Listen Later Dec 21, 2021 10:00

Dr. Sara Tolaney is chief of the Division of Breast Oncology and associate director of the Susan F. Smith Center for Women's Cancers at the Dana-Farber Cancer Institute, as well as associate professor of medicine at Harvard Medical School. The 2021 San Antonio Breast Cancer Symposium featured four days of presentations on the latest research on breast cancer. Dr. Tolaney joined us to discuss the research that is most immediately applicable to people who've been diagnosed with the disease. Listen to the episode to hear Dr. Tolaney explain: results of an early study looking at how effective the experimental medicine datopotamab deruxtecan was in treating metastatic, triple-negative breast cancer a study comparing Enhertu (chemical name: fam-trastuzumab-deruxtecan-nxki) to Kadcyla (chemical name: T-DM1 or ad-trastuzumab emtansine) for metastatic, HER2-positive breast cancer that had spread to the brain the studies that she thinks are practice-changing

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Journal Review in Breast Surgery: Management of Residual Disease After Neoadjuvant Chemotherapy

Play Episode Listen Later Dec 13, 2021 19:40

Why should a surgeon care about breast cancer chemotherapy trials? Join Drs. Michael Alvarado, Rita Mukhtar, and Alexa Glencer as they discuss the benefits of neoadjuvant chemotherapy over upfront surgery and the role of adjuvant chemotherapy for select patients who harbor residual disease at the time of surgery. Learning objectives: - Understand the benefits conferred by neoadjuvant chemotherapy compared to upfront surgery in certain patients with breast cancer - Learn about the study design and results of the CREATE-X phase 3 randomized controlled trial comparing adjuvant capecitabine to standard therapy in patients with HER2 negative invasive breast cancer with residual disease following cytotoxic neoadjuvant chemotherapy - Describe the specific benefit of adjuvant capecitabine for triple negative breast cancer patients and discuss its evolving role with recent FDA approval of neoadjuvant pembrolizumab in this group - Learn about the study design and results of the KATHERINE phase 3 randomized controlled trial comparing adjuvant T-DM1 to trastuzumab in patients with HER2+ invasive breast cancer with residual disease following cytotoxic and HER2-targeted neoadjuvant chemotherapy Journal article links: CREATE-X: https://www.nejm.org/doi/full/10.1056/NEJMoa1612645 KATHERINE: https://www.nejm.org/doi/full/10.1056/NEJMoa1814017 Please visit behindtheknife.org to access other high-yield surgical education podcasts, videos and more.

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Season 2 Game 16: Bruce Minne

The Huddle by Tip-Off

Play Episode Listen Later Dec 12, 2021 58:28

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The Clinical Playbook: Team-based Integration of ADCs in Metastatic NSCLC

ReachMD CME

Play Episode Listen Later Nov 30, 2021

CME credits: 1.00 Valid until: 29-11-2022 Claim your CME credit at https://reachmd.com/programs/cme/clinical-playbook-team-based-integration-adcs-metastatic-nsclc/12841/ One area of recent progress in the treatment of non–small cell lung cancer (NSCLC) is the development of HER2 targeted therapies for the rare, emerging genetic variant, ERBB2 (HER2) mutations. In fact, the NCCN lists ERBB2 (HER2) mutations as an emerging biomarker to identify novel therapies for patients with metastatic NSCLC. The HER2-directed antibody-drug conjugates (ADC) ado-trastuzumab emtansine (T-DM1) and fam-trastuzumab deruxtecan-nxki are now listed as available targeted agents with activity against HER2 mutations. ADCs with other targets such as Trop-2 and HER3 are now also under investigation and showing promise in NSCLC. ADCs have the potential to increase treatment choices for patients with mNSCLC. For practicing clinicians, this evolution of HER2-directed therapy and ADCs will add to the complexity of NSCLC treatment. This activity will review the emerging role and potential application of ADCs in mNSCLC, including HER2 as a target in NSCLC, biomarker testing, HER2-, HER3-, and TROP2-targeted ADCs, available clinical data on safety and efficacy, evidence-based guideline recommendations, and how newer targeted agents may fit into the treatment paradigm for patients with mNSCLC.

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The Clinical Playbook: Team-based Integration of ADCs in Metastatic NSCLC

ReachMD CME

Play Episode Listen Later Nov 30, 2021

Much-Anticipated Phase 3 DESTINY-Breast03 Trial / Phototherapy for Psoriasis and More!

Physician's Weekly Podcast

Play Episode Listen Later Oct 4, 2021 37:39

Welcome to this episode of Physician's Weekly Podcast, in collaboration with Physician's Weekly. We have 3 fantastic in-depth interviews for you this week. The European Society of Medical Oncology ended a few days ago and later in this episode, I had the opportunity to speak with Dr. Javier Cortes, in Barcelona, Spain about his Presidential Symposium late-breaking presentation held at that meeting, in which he revealed the data from the much-anticipated phase 3 DESTINY-Breast03 trial for patients with advanced breast cancer. The results of the antibody-drug conjugate trastuzumab deruxtecan compared head-to-head with the current standard, called TDM1, were practice-changing, with spectacular efficacy (I am not sure I have ever seen a P-value with 22 zeros) and excellent safety outcomes.Also in this episode, our correspondent Dylan Prentner speaks with pediatrician Umbereen Nehal, who was Chief Medical Officer and Vice President of Medical Affairs for Community Healthcare Network in New York city. In addition, Dr. Nehal led a nationwide campaign as chair of the Task Force of American Muslims for Affordable Health Care that was conducted in conjunction with the White House, where she leveraged community resources to educate and enroll American Muslims in new health coverage options. In recognition of this work, Nehal was honored by an invitation from President Barack Obama to the White House. Dr. Nehal talks with us about how to find the balance of hope and humanism in what she says is a system of perverse incentives.But first, Physician's Weekly speaks with dermatologist Dr Sophie Weatherhead from Newcastle, UK about their recently published research in phototherapy and psoriasis . Further reading:Watson N, Wilson N, Shmarov F, Zuliani P, Reynolds NJ, Weatherhead SC. The use of psoriasis biomarkers, including trajectory of clinical response, to predict clearance and remission duration to UVB phototherapy. J Eur Acad Dermatol Venereol. 2021 Jul 13. doi: 10.1111/jdv.17519. Epub ahead of print. PMID: 34255884.Let us know what you thought of this week's episode on Twitter: @physicianswkly Want to share your medical expertise, research, or unique experience in medicine on the PW podcast? Email us at editorial@physweekly.com! Thanks for listening!

Voces de la ciencia Ep 04 Temporada 2

Voces de la ciencia

Play Episode Listen Later Aug 24, 2021 3:46

Tolerabilidad y seguridad con TDM1

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4.12 Real-World Survival Outcomes for Pertuzumab and T-DM1 with Dr. Josee-Lyne Ethier

Plenary Session

Play Episode Listen Later Aug 3, 2021 35:50

Today we interview Dr. Josee-Lyne Ethier of Queen's University in Kingston, Ontario, Canada on her new paper "Practice Patterns and Outcomes of Novel Targeted Agents for the Treatment of ERBB2-Positive Metastatic Breast Cancer", out now in JAMA Oncology. We talk about the real-world survival outcomes for pertuzumab and T-DM1, comparing these outcomes to the results of pivotal clinical trials CLEOPATRA and EMILIA. Practice Patterns and Outcomes: doi.org/10.1001/jamaoncol.2021.2140 Back us on Patreon! www.patreon.com/plenarysession Check out our YouTube channel: www.youtube.com/channel/UCUibd0E2kdF9N9e-EmIbUew

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HER2-Positive Localized Breast Cancer | Oncology Today with Dr Neil Love: HER2-Positive Localized Breast Cancer

Play Episode Listen Later May 19, 2021 30:54

Featuring an interview with Dr Adam M Brufsky, including the following topics: Personalized medicine for HER2-positive early breast cancer (0:00) Case: A woman in her early 60s with ER/PR-positive, HER2-positive invasive ductal carcinoma who receives T-DM1 and neratinib (21:40) Case: A woman in her mid-40s with ER/PR-positive, HER2-positive early breast cancer (23:48) Case: A woman in her late 50s with ER/PR-negative, HER2-positive early breast cancer (26:10) CME information and select publications

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HER2-Positive Breast Cancer | Cancer Conference Update: What Happened at the 2020 San Antonio Breast Cancer Symposium® — HER2-Positive Breast Cancer (Session 2)

Play Episode Listen Later May 4, 2021 58:10

Featuring perspectives from Dr Mark D Pegram on the following topics: Case presentations and San Antonio Breast Cancer Symposium (SABCS®) review of locally advanced and high-risk HER2-positive breast cancer Introduction (0:00) Case: A 49-year-old woman who received neoadjuvant TCHP, currently awaiting surgery — Estelamari Rodriguez, MD, MPH (5:12) Case: A 55-year-old woman with Stage I HER2-positive breast cancer — Kelly Yap, MD (23:46) Case: A 45-year-old woman who received postoperative T-DM1 after neoadjuvant TCHP — Philip Glynn, MD (26:30) Case: A 39-year-old woman with localized disease and a positive cervical node on PET scan — Dr Rodriguez (32:00) Case presentations and SABCS review of metastatic HER2-positive breast cancer Case: A 70-year-old woman with a 10-cm Grade III, ER/PR-negative, HER2-positive infiltrating ductal carcinoma and pleural metastases — Alan B Astrow, MD (38:24) Case: An 87-year-old woman with pretreated HER2-positive metastatic breast cancer now with negative (low) HER2 — Yanjun Ma, MD (43:25) Case: A 60-year-old woman with malignant pericardial effusion — Dr Glynn (50:23) Case: A 43-year-old woman who develops brain metastases after prior TCHP — Dr Yap (53:09) CME information and select publications

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HER2-Positive Breast Cancer | Striving for Consensus on the Optimal Management of HER2-Positive Breast Cancer

Play Episode Listen Later Apr 6, 2021 89:38

Featuring a roundtable discussion with Drs Virginia F Borges, Sara Hurvitz and Ian E Krop, including the following topics: Introduction Impact of COVID-19 vaccinations on screening for breast cancer (0:00) Management of HER2-positive early breast cancer Case: A woman in her early 40s with ER/PR-positive, HER2-positive breast cancer achieves a pathologic complete response with docetaxel/trastuzumab/pertuzumab — Alan B Astrow, MD (6:30) Therapeutic approach for patients with HER2-positive breast cancer and residual disease after neoadjuvant therapy (10:04) Case: A woman in her early 70s with Grade III, ER/PR-negative, HER2-positive breast cancer develops shortness of breath after neoadjuvant chemotherapy — Dr Astrow (19:57) Disease-specific factors in the selection of neoadjuvant therapy for patients with HER2-positive breast cancer (28:00) Selection of HER2-targeted therapy in the adjuvant setting (33:31) Selection and sequencing of therapies for HER2-positive metastatic breast cancer Case: A woman in her early 40s with HER2-positive breast cancer and brain metastases — Yanjun Ma, MD (36:11) Case: A woman in her mid-30s with ER/PR-positive, HER2-positive breast cancer and brain metastases — Estelamari Rodriguez, MD, MPH (40:56) Case: A woman in her mid-60s who presents with a large, ulcerated breast mass and is diagnosed with HER2-positive breast cancer and liver metastases — Dr Astrow (48:38) Choice of initial therapy for patients with metastatic HER2-positive breast cancer (55:08) Management of HER2-positive breast cancer with brain metastases; intracranial activity of tucatinib in patients with metastatic HER2-positive breast cancer (1:00:00) CNS penetration and intracranial response with the antibody-drug conjugates trastuzumab deruxtecan and T-DM1; efficacy and tolerability of neratinib after disease progression on tucatinib (1:07:28) Perspective on the use of hormonal therapy for patients with ER/PR-positive, HER2-positive breast cancer (1:12:45) Efficacy of PARP inhibitors in patients with HER2-positive breast cancer and BRCA mutations; emerging data from the OlympiA trial evaluating olaparib as adjuvant therapy for patients with HER2-negative breast cancer and germline BRCA mutations (1:18:53) Benefits and risks of the novel anti-HER2 antibody margetuximab for patients with HER2-positive advanced breast cancer (1:25:10) CME information and select publications

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Breast Cancer | Oncology Today with Dr Neil Love: Newly Approved Agents in HER2-Positive Metastatic Breast Cancer

Play Episode Listen Later Mar 5, 2021 70:16

Featuring an interview with Dr Mark D Pegram on the following topics: Newly approved agents in HER2-positive metastatic breast cancer (mBC) (0:00) Clinical data with neratinib for patients with mBC and HER2 mutations (22:31) Optimal integration of margetuximab into the treatment algorithm for patients with HER2-positive mBC (26:31) Case: A woman in her late 50s receives multiple lines of HER2-directed therapies for HER2-positive mBC (29:30) Mechanism of action of a novel antibody-based construct linking trastuzumab and toll-like receptors (36:49) Case: A woman in her early 70s receives trastuzumab deruxtecan for HER2-positive mBC (40:48) Monitoring for and management of interstitial lung disease associated with trastuzumab deruxtecan (44:21) Efficacy of trastuzumab deruxtecan, tucatinib and T-DM1 in patients with HER2-positive mBC (47:45) Case: A woman in her mid-50s receives tucatinib/trastuzumab/capecitabine for HER2-positive breast cancer with metastases in the brain (56:10) Management of side effects of tucatinib/capecitabine/trastuzumab for HER2-positive mBC (1:02:36) Potential role of margetuximab in the treatment of HER2-positive breast cancer (1:05:53) CME information and select publications

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#137_Vídeo-MOC_VOL 11 Nº14 | CA Mama na Prática (Caso 02) - Manejo CA Mama HER-2 positivo localizado

MOC Brasil

Play Episode Listen Later Sep 24, 2020 3:33

Os desfechos alcançados no tratamento do câncer de mama HER-2 positivo localizado vêm em constante evolução, tanto pela inclusão de novas drogas nesse cenário, como também pela seleção mais específica de terapias contemplando não só características da doença ao diagnóstico, mas também o grau de resposta patológica apresentado após o tratamento neoadjuvante. Confira neste episódio uma discussão enriquecedora sobre os dados relevantes no tratamento do câncer de mama HER-2 positivo localizado, com apresentação do Dr. Nivaldo Farias Vieira, diretor técnico-científico da clínica ONCOHEMATOS, e moderação do Dr. Antonio C. Buzaid, editor do MOC. Assista também ao Vídeo-MOC na íntegra, com apresentação deste caso clínico e uma revisão sobre os dados do estudo KRISTINE, que avaliou o uso de quimioterapia associada ao duplo bloqueio anti-HER-2 versus T-DM1 associado a pertuzumabe como tratamento neoadjuvante na doença localizada. https://mocbrasil.com/blog/videos-moc/vol11num14/

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Breast Cancer | Oncology Grand Rounds Series: Part 1 — Breast Cancer (Webinar Proceedings)

Advances in Women's Health

Play Episode Listen Later Jul 16, 2020 83:00

Proceedings from the first in a series of 11 integrated webinars held in association with the 2020 ONS Annual Congress. Featuring perspectives from Dr Virginia Kaklamani, Ms Marissa Marti, Dr Joyce O’Shaughnessy and Mr Daniel G Pizana. Introduction (00:00) Neoadjuvant therapy for patients with localized HER2-positive breast cancer (2:20) Activity and tolerability of T-DM1 as adjuvant therapy (7:24) Clinical experience with neratinib as postadjuvant therapy for patients with HER2-positive breast cancer (11:00) Results of the KATHERINE study comparing T-DM1 to trastuzumab and the APHINITY trial evaluating pertuzumab, trastuzumab and chemotherapy as adjuvant therapy for HER2-positive early breast cancer (15:48) Benefits and risks with the novel agents trastuzumab deruxtecan and tucatinib for HER2-positive metastatic breast cancer (mBC) (26:13) Role of the immune checkpoint inhibitors atezolizumab and pembrolizumab and the novel antibody-drug conjugate sacituzumab govitecan for triple-negative breast cancer (38:49) Genomic testing for patients with breast cancer; integration of PARP inhibitors into the therapeutic algorithm for patients with mBC and germline BRCA mutations (52:59) Efficacy and tolerability of the CDK4/6 inhibitors palbociclib, abemaciclib and ribociclib for ER-positive, HER2-negative mBC (1:07:56) Activity of alpelisib in patients with ER-positive mBC and PIK3CA mutations; results of the SOLAR-1 trial evaluating alpelisib with fulvestrant (1:16:19) CNE information and select publications

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Emerging Roles for Immunotherapy in HER2+ Breast Cancer

Play Episode Listen Later Jun 30, 2020

Guest: Sara Tolaney MD, MPH What do we know now about the potential safety and tolerability of administering T-DM1 with pembrolizumab to patients with HER2+ breast cancer? Breast medical oncologist at the Dana-Farber Cancer Institute and Assistant Professor of Medicine at Harvard Medical School Dr. Sara Tolaney explains these findings from her study that was presented at the 2020 ASCO Annual Meeting.

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Emerging Roles for Immunotherapy in HER2+ Breast Cancer

Advances in Women's Health

Play Episode Listen Later Jun 30, 2020

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Dr. Neelima Denduluri Discusses Key Abstracts on Breast Cancer from the #ASCO20 Virtual Scientific Program

Play Episode Listen Later Jun 11, 2020 20:04

Dr. Neelima Denduluri, a medical oncologist at Virginia Cancer Specialists and Associate Chair of the Breast Cancer Research for the US Oncology Network, discusses key abstracts in the breast cancer field that were featured at the ASCO20 Virtual Scientific Program. Transcript ASCO Daily News: Welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. Joining me today is Dr. Neelima Denduluri, a medical oncologist at Virginia Cancer Specialists and Associate Chair of Breast Cancer Research for the US Oncology Network. Dr. Denduluri serves on the editorial board of the ASCO Daily News, and will highlight key abstracts that were featured at the ASCO20 Virtual Scientific Program. Dr. Denduluri has received institutional research funding from Amgen, Novartis, Genentech, Eli Lilly, Pfizer, Daiichi Sankyo, Seattle Genetics and Immunomedics. Full disclosures relating to all Daily News podcasts can be found on our episode pages. Dr. Denduluri, it's great to have you on the podcast today. Dr. Neelima Denduluri: Thank you, Geraldine, for asking me to participate on the podcast. ASCO Daily News: Let's start with advanced breast cancer. Can you tell us about the key abstracts that address this patient population? Dr. Neelima Denduluri: Absolutely. So this year's ASCO was filled with many rich advancements across the therapeutic, diagnostic, and symptom management spectrum, which is always wonderful when we're trying to treat our patients adequately. In advanced breast cancer, one abstract that generated significant interest is whether surgery improves outcomes in patients that present with advanced breast cancer. Generally, the paradigm in advanced breast cancer is to give systemic therapy. We've always wondered, does taking out the local site of disease or the primary tumor, in terms of the breast tumor and lymph nodes, and possibly giving radiation, does that improve outcomes in advanced breast cancer? Well, the late-breaking abstract 2 (LBA2), presented by Dr. Khan, looked at women or men who presented with stage IV de novo breast cancer. And these patients obviously started their appropriate systemic therapy based on the subtype of breast cancer. And these patients, after three to six months, were randomized to continue the systemic therapy or stop their systemic therapy for local management before resuming their systemic therapy. And what the study showed is that those patients that did receive local therapy did not have an improvement in survival compared with those patients that did not receive local therapy to their breasts and/or lymph nodes. So I think that was an excellent lesson for all of us. And how it guides our management is to say that the vast majority of our patients with advanced breast cancer do not need to undergo surgery to improve outcomes. Now, having said that, about 25% of patients that did not have any local therapy did have some progression. And so for those patients, despite no improvement in long-term quality of life, it is something that we should consider and talk about with them. Especially if that is the only site of disease that is progressing, should we go ahead and give them some palliation in terms of symptoms in the short term. The most common subtype of advanced breast cancer that we treat is hormone receptor positive, HER2 negative breast cancer. There are data that have been previously presented that show that fulvestrant, which is an injectable selective estrogen receptor downgrader, is possibly superior to aromatase inhibitors. So one trial evaluated this concept, but in the face of CDK4/6 inhibition. CDK4/6 inhibitors have become the mainstay of therapy in advanced hormone receptor positive, HER2 negative breast cancer. What abstract 1007, or the PARSIFAL trial, looked at was is fulvestrant and a CDK4/6 inhibitor superior to an aromatase inhibitor and CDK4/6 inhibitor. And what they showed is that, in advanced breast cancer, fulvestrant was not superior to an aromatase inhibitor when given in combination with CDK4/6 inhibition. And this is something that I think was reassuring to patients, especially if they have to come in to the clinic to receive an injection. What will be interesting going forward is how do selective estrogen receptor downgraders that are oral come into play, and how do they compare with fulvestrant or how do they compare with aromatase inhibitors. So that was something that was quite reassuring, that we can give aromatase inhibitors with CDK4/6 inhibitors without compromising efficacy in patients with advanced breast cancer. Another trial that generated some excitement for our patients and therapeutic options is the BYLieve trial, or abstract 1006. As I stated earlier, the mainstay of therapy for those patients with advanced breast cancer that's hormone receptor positive and HER2 negative is some type of endocrine partner, whether it be tamoxifen, fulvestrant, or an aromatase inhibitor and a CDK4/6 inhibitor. Mainly, it's an aromatase inhibitor and a CDK4/6 inhibitor. So for those patients that progress on that regimen, what do we do next is something that comes up. We know that up to 40% of patients with advanced breast cancer that's hormone receptor positive and HER2 negative have PI3-kinase mutations, and alpha-specific PI3-kinase inhibitor that has shown to improve outcomes in patients with advanced breast cancer that have PI3-kinase mutations. What the BYLieve trial looked at was how about after CDK4/6 inhibition. And what it showed is that patients that received CDK4/6 inhibition and fulvestrant and alpelisib did have about a 50% chance of not progressing at six months. And there was about a seven-month progression-free survival benefit in these patients. The toxicities that we know of with alpelisib include rash, diarrhea, and hypoglycemia. And those side effects were reported less than in the SOLAR-1 trial. So we know that, in this group of patients, we really do need to monitor their blood sugars, give them prophylactic antihistamines, and also counsel them on adequate anti-diarrheal management. So the BYLieve trial helped us with two concepts. One is, after CDK4/6 inhibition, in those patients with PI3-kinase mutations, yes, there is a role for alpelisib. And the second thing is that we're doing a better job, while we can't do cross-trial comparisons, of improving the quality of life and symptoms that arise from alpelisib, including the rash, the diarrhea, and the hypoglycemia. Another trial that was very exciting, shifting gears, is the HER2CLIMB trial. And that was abstract 1005. We knew from December that tucatinib improves outcomes when added to trastuzumab and capecitabine in patients with advanced HER2 positive breast cancer. We also knew that it does improve survival irrespective of brain metastases, and brain metastases that might have been progressing. What this analysis of the HER2CLIMB showed was that the patients that received tucatinib did have an improved survival benefit compared with trastuzumab and capecitabine of six months. Additionally, the response rate solely in the central nervous system was 41% on the tucatinib arm versus 23% on the arm that received capecitabine and trastuzumab alone. So these were really exciting data because we do know that about 50% of patients with advanced stage IV breast cancer that's HER2 positive do eventually develop brain metastases. So while we know that tucatinib, in addition to trastuzumab and capecitabine, does improve survival irrespective of brain metastases, we know now that those patients with progressing brain metastases do have an improved outcome when tucatinib is added. The side effects that we have to monitor for are diarrhea and liver function abnormalities, of course. Shifting gears a little bit more is the immunotherapy trial in triple-negative breast cancer. And that is abstract 1000. So over the past 12 to 18 months, we've seen data from the IMpassion130 trial, which showed that patients who had PD-L1 positivity in their immune cells did derive benefit when atezolizumab was added to nab-paclitaxel, and it did improve outcomes. Now, this trial, the KEYNOTE-355 trial, looked at patients that were untreated for their advanced breast cancer. And these patients were randomized to paclitaxel, nab-paclitaxel, or gemcitabine and carboplatin chemotherapy with pembrolizumab or without pembrolizumab. And what was noted is those patients that had a combined positive score of PD-L1 greater than or equal to 10 derived about a four-month progression-free survival benefit if they received pembrolizumab. Now, we have two trials, the IMpassion trial and the KEYNOTE trial, that show that patients with some element of PD-L1 expression, whether it's the immune cells, as evidenced by the IMpassion trial, or the combined positive score of PD-L1, as was evaluated in the KEYNOTE trial, did have significantly better outcomes if immunotherapy was incorporated as first-line treatment for their triple-negative breast cancer. There are questions, though, that we have to answer, in what is the optimal measurement to predict response to immunotherapy in the triple-negative breast cancer setting, and also what is the optimal cut point that we should use to say whether we should employ immunotherapy. However, it was another advancement for an unmet need, which is triple-negative breast cancer. One thing we know in advanced breast cancer, whether it's because of PI3-kinase mutations, whether it's measuring PD-L1, that we need to do testing beyond estrogen receptor, progesterone receptor, and HER2. We're increasingly utilizing genomic and germline testing to see if we can give more personalized therapy to our patients. 1002 looked at the effectiveness of patients with BRCA mutations that were somatic, as well as patients with germline mutations, including PALB2, and they found that olaparib did improve outcomes in patients with somatic BRCA mutations, as well as those patients that harbored PALB2 mutations. So I think that this is another reason for us to make sure that we are sending our patients for germline testing in the advanced breast cancer setting, as well as to make sure that we're looking for somatic mutations that we can target. ASCO Daily News: What are your key takeaways from the studies on early breast cancer? Dr. Neelima Denduluri: Thanks for asking that question. As I said earlier, there are many advancements, but one that I want to highlight is abstract 501. We know that anthracyclines have improved survival in breast cancer over the last several decades. However, we also know that HER2-targeted therapy using trastuzumab, pertuzumab, and now TDM1 has significantly improved outcomes in early breast cancer. So we've never known whether we truly need to give anthracyclines in the face of effective HER2-targeted therapy. The TRAIN-2 trial, which is abstract 501, evaluated whether anthracyclines improve outcomes when there is optimal HER2-targeted therapy. And the answer is no, it did not. So I think that's very promising. And potentially, what we'll be able to do is to decrease cardiotoxicity, as well as treatment-related leukemias and myelodysplasia, possibly, in terms of reducing the risk of those by omitting anthracyclines in the early HER2 breast cancer setting. Another abstract that I want to highlight is 507, which was looking at the role of adjuvant capecitabine in a metronomic fashion, meaning lower doses and giving it for a longer period of time, in those patients with triple-negative breast cancer. Just to give a quick historical background, we know from the CREATE-X trial that those patients that received preoperative therapy with third-generation chemotherapy and had residual disease at the time of surgery, those patients did benefit from the addition of capecitabine as part of their adjuvant treatment, compared with no adjuvant treatment. So these are further data that we have further elucidating the role of capecitabine, primarily in the triple-negative breast cancer setting. And we did see that there was an improved outcome in terms of disease-free survival in these patients with anatomic stage I to III triple-negative breast cancer, and they did benefit from the addition of capecitabine. Also, two side effects that we worry about with capecitabine are diarrhea and hand-foot syndrome. And they seem to be more manageable with this lower dose of capecitabine compared with the traditional 2,500 mgs per meter squared twice a day that was approved initially with capecitabine or that was used in CREATE-X. ASCO Daily News: Dr. Denduluri, are there any new advancements in supportive care and symptom management? Dr. Neelima Denduluri: So Geraldine, we know that a geriatric assessment is very important when we treat our patients that are elderly. Abstract 12009 performed a geriatric assessment on patients that had stage III or IV cancer and were aged 70 or older. And once they performed that geriatric assessment, they sent the treating oncologist the geriatric assessment and guided recommendations to improve their tolerance to therapy, potentially. And what they found is that it reduced clinically graded grade III to V toxicities significantly by providing this geriatric assessment. And also, it didn't lower survival. So I thought that this was really nice prospective data that shows that we should be performing a geriatric assessment, and what we find, we should make sure to support our patients better based on the findings. And this improves our patients' tolerability to therapy, and it does not decrease their survival. So I thought that that was a very uplifting trial. We have a lot of programs around the country that are saying how best do we support our geriatric population, and this was a good step in the right direction. ASCO Daily News: Absolutely. Is there anything else you'd like to add today? Any other abstracts that we should know about? Dr. Neelima Denduluri: A couple of other things that we talk about quite a bit in our clinic is disparities. And abstract 1080 found that those patients with triple-negative breast cancer were continuing to receive non-guideline-adherent care when it was compared to their Caucasian population compared with the black population. So I think that this underscores that we really need to make sure that we address the disparities in cancer care. Cancer survivorship is very important. One thing that patients complain about is insomnia. Abstract 12005 showed that yoga, cognitive behavioral therapy, and survivorship health education really improved insomnia in cancer survivors. So again, when we look at taking care of patients, we really need to look at the whole spectrum. And while we have excellent drugs and drug development that is improving outcomes, we also need to make sure that disparities, financial toxicity, survivorship are addressed. And therefore, I thought that this ASCO did a great job of looking at those issues, as well as drug development. ASCO Daily News: Absolutely. Well, thank you, Dr. Denduluri, for sharing your insights with us today on these promising new developments in the breast cancer field. Dr. Neelima Denduluri: Thank you, Geraldine. ASCO Daily News: And thanks to our listeners for joining us today. If you're enjoying the content on the podcast, please take a moment to rate and review us on Apple 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Oncotarget: Second Line Trastuzumab Emtansine Following Horizongal Dual Blockade

Oncotarget

Play Episode Listen Later Jun 3, 2020 3:55

Volume 11, Issue 22 of Oncotarget reported that despite relevant medical advancements, metastatic breast cancer remains an incurable disease. HER2 signaling conditions tumor behavior and treatment strategies of HER2 expressing breast cancer. Cancer treatment guidelines uniformly identify dual blockade with pertuzumab and trastuzumab plus a taxane as best first line and trastuzumab emtansine as a preferred second-line choice. However, there is no prospectively designed available study focusing on the sequence and outcomes of patients treated with T-DM1 following the triplet. In the following report, data concerning a wide series of patients treated in a real-life setting are presented. Results obtained in terms of response and median progression-free survival suggests a significant role for T-DM1 in disease control of metastatic HER2 expressing breast cancer. Dr. Salvatore Del Prete from the Medical Oncology Unit “San Giovanni di Dio” Hospital, Frattamaggiore as well as Dr. Liliana Montella from the Medical Oncology Unit “Santa Maria delle Grazie” Hospital said, "From the 80s, Human Epidermal Growth Factor Receptor 2 (HER2) signaling was increasingly recognized as pivotal in tumor growth of HER2 expressing breast cancer. HER2 expression is limited to a proportion (15–20%) of breast cancer; however, HER2 conditions tumor behavior and addresses treatment strategies." Currently available guidelines in metastatic HER2 positive breast cancer design a sequence of treatment with first-line double blockade with trastuzumab plus pertuzumab and a taxane according to Cleopatra trial results and second-line treatment with trastuzumab emtansine enforced by Emilia trial results and, then, lapatinib plus capecitabine. The reduced toxicity of T-DM1 in the second and later lines of treatment together and the high rates of activity and efficacy are determinant in choosing treatment for a patient candidate to a prolonged time on treatment. On February 22, 2013, the Food and Drug Administration approved T-DM1 for use as a single agent in the treatment of patients with HER2-positive metastatic breast cancer who previously received trastuzumab and a taxane. Such results induced FDA on May 3, 2019, to approve T-DM1 for the adjuvant treatment of patients with HER2-positive early breast cancer treated with neoadjuvant taxane and trastuzumab-based treatment and having a residual invasive disease in the breast or axilla at the surgery. In the present study, data coming from different centers concerning patients with HER2 positive metastatic breast cancer treated with second-line T-DM1 following trastuzumab and pertuzumab were collected and evaluated. The Del Prete/Montella Research Team concluded in their Oncotarget Research Article that despite the increased rate of survival of metastatic breast cancer patients overall, a rate of patients is lost at any line of therapy. In two different studies concerning patients series treated predominantly before 2010, 3% and 26% of patients reached the goal of third-line treatment. This evidence underscores the need to give our patients the best treatment as early as possible. Summarizing, the available evidence is substantially in favor of the choice of T-DM1 in the treatment of HER2 breast cancer at second and later lines. DOI - https://doi.org/10.18632/oncotarget.27603 Full text - https://www.oncotarget.com/article/27603/text/ Correspondence to - Salvatore Del Prete - salvatore.delprete@aslnapoli2nord.it and Liliana Montella - liliana.montella@aslnapoli2nord.it About Oncotarget Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget

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Lung Cancer | iJournal Club: Optimizing Therapy for Patients with Metastatic Squamous Cell Carcinoma of the Lung

Play Episode Listen Later Mar 18, 2020 72:28

Featuring perspectives from Dr Shirish M Gadgeel on the later-line management of metastatic squamous cell carcinoma of the lung. Recent advances in the management of advanced non-small cell lung cancer (NSCLC) (0:00) Case: A woman in her early 70s with metastatic squamous cell carcinoma (SCC) of the lung receives carboplatin/paclitaxel and pembrolizumab as first-line therapy on the KEYNOTE-021 trial (02:25) Response to pembrolizumab and chemotherapy in advanced SCC of the lung (04:34) Efficacy of pembrolizumab alone or in combination with chemotherapy for advanced NSCLC (07:41) Choice of immune checkpoint inhibitor/chemotherapy regimen as first-line therapy for metastatic SCC of the lung (12:22) Results of the Phase III CheckMate 227 trial evaluating nivolumab alone, with ipilimumab or with chemotherapy as first-line therapy for metastatic NSCLC (15:43) Interim overall survival analysis of the Phase III IMpower110 study investigating atezolizumab versus platinum-based chemotherapy for metastatic NSCLC in the first-line setting (18:32) Cancer site and adverse events induced by immune checkpoint inhibitors (20:05) Genetic alterations in patients with SCC of the lung; rationale for targeting the ERBB signaling pathway (22:18) Results of the Phase III LUX-Lung 8 trial of afatinib versus erlotinib as second-line treatment for advanced SCC of the lung (25:53) Secondary analysis of LUX-Lung 8: Association of ERBB mutations with clinical outcomes among patients with afatinib- or erlotinib-treated SCC of the lung (28:04) Role of HER2 mutations and HER2 amplification in patients with NSCLC; incidence of HER2 alterations in patients with SCC of the lung (30:14) Targeting HER2 alterations with the tyrosine kinase inhibitors afatinib and dacomitinib in patients with NSCLC (34:15) Efficacy of the antibody-drug conjugate trastuzumab deruxtecan (DS-8201) in patients with NSCLC and HER2 alterations (36:11) Activity of T-DM1 in patients with NSCLC and HER2 mutations (38:04) Management of gastrointestinal side effects associated with afatinib (40:22) Activity of afatinib in heavily pretreated ERBB2 mutation-positive advanced NSCLC (43:01) Afatinib in patients with metastatic or recurrent lung cancer with HER2 mutations (45:15) Case: A man in his early 80s develops metastases to the liver during treatment with durvalumab after chemoradiation therapy for Stage III SCC of the lung and is found to have FGFR1 amplification (47:15) FGFR signaling as a target for NSCLC therapy; outcomes with the FGFR inhibitor AZD4547 in patients with metastatic SCC of the lung and FGFR alterations (51:04) SWOG-S1400 Lung Cancer Master Protocol (Lung-MAP) — Biomarker-targeted therapy for patients with previously treated Stage IV SCC of the lung (56:02) Case: A woman in her early 50s with ALK-rearranged metastatic lung adenocarcinoma experiences a dramatic response to crizotinib on the PROFILE 1014 study (1:02:39) Response to ALK inhibitors for ALK-rearranged metastatic NSCLC (1:06:54) CME information and select publications

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Breast Cancer | Visiting Professors: Investigator Perspectives on Recently Approved and Emerging Strategies in the Management of Breast Cancer

Play Episode Listen Later Mar 12, 2020 45:18

A presentation on breast cancer featuring perspectives from Dr Sara Hurvitz. Introduction (00:00) Chemotherapy with Immunotherapy as First-Line Treatment for Metastatic Triple-Negative Breast Cancer (00:53) T-DM1 for Residual HER2-Positive Disease After Neoadjuvant Therapy (12:17) PARP Inhibitors in Metastatic Breast Cancer (19:37) PI3 Kinase Inhibitors in Hormone Receptor-Positive Metastatic Disease (26:47) Novel HER2-Directed Investigational Approaches (34:15) CME information and select publications

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HER2-Positive Breast Cancer | Data + Perspectives: Clinical Investigators Explore the Current and Future Management of HER2-Positive Breast Cancer

Play Episode Listen Later Mar 6, 2020 88:33

Proceedings from a satellite symposium during the 42nd annual San Antonio Breast Cancer Symposium. Featuring perspectives from Drs Adam M Brufsky, Lisa A Carey, Sara Hurvitz and Martine J Piccart-Gebhart. Introduction Program Overview: Dr Love (00:00) Considerations in the Care of Patients with Localized HER2-Positive Breast Cancer (BC) Receiving Neoadjuvant Systemic Therapy Case (Dr Brufsky): A woman in her mid-30s with an ER-positive, HER2-positive, node-negative IDC receives neoadjuvant TCHP and at surgery is found to have residual disease in the breast (10:40) Case (Dr Carey): A woman in her mid-80s with a large ER-positive, HER2-positive, node-positive IDC has difficulty tolerating neoadjuvant therapy and has a small amount of residual disease in the breast at surgery (13:10) Faculty Presentation: Dr Carey (16:53) Adjuvant and Extended-Adjuvant Therapy for Patients with Localized HER2-Positive BC Case (Dr Brufsky): A woman in her early 60s with a 1.5-cm, ER-positive, HER2-positive IDC and 3 positive sentinel nodes (30:51) Case (Dr Carey): A woman in her mid-40s with ER-negative, HER2-positive, node-negative BC receives adjuvant T-DM1 on the ATTEMPT trial (36:54) Faculty Presentation: Dr Piccart-Gebhart (42:11) Available Therapeutic Options for the Management of HER2-Positive Metastatic BC (mBC) Case (Dr Hurvitz): A woman in her early 60s with HER2-positive mBC to the liver achieves a complete response to THP → HP but develops CNS metastases 3 years later (52:43) Case (Dr Piccart-Gebhart): A woman in her late 30s with heavily pretreated ER-positive, HER2-positive mBC receives neratinib/letrozole (55:07) Faculty Presentation: Dr Brufsky (57:51) Novel Agents and Strategies Under Evaluation for Patients with HER2-Positive mBC Case (Dr Hurvitz): A woman in her late 40s with ER-positive, HER2-positive mBC receives trastuzumab deruxtecan on a clinical trial after disease progression on multiple lines of therapy (1:09:56) Case (Dr Piccart-Gebhart): A woman in her late 20s receives multiple lines of local and systemic therapy for ER-positive, HER2-positive mBC (1:11:29) Faculty Presentation: Dr Hurvitz (1:13:41) CME information and select publications

Breast Cancer | Charles E Geyer Jr, MD

Jornal da USP no ar: Medicina

Play Episode Listen Later Nov 4, 2019 78:18

Breast Cancer Update for Surgeons, Issue 1, 2019 — Part #1: Our interview with Dr Geyer highlights the following topics as well as cases from his practice: Case: A premenopausal woman in her mid-40s with Grade II, ER/PR-positive, HER2-negative lobular breast cancer, a 21-gene assay Recurrence Score (RS) of 10 and a deleterious CHEK2 mutation undergoes a bilateral mastectomy (00:00) Impact of gene-expression assay results on therapeutic decision-making (04:54) Results of the Phase III TAILORx trial evaluating chemoendocrine therapy versus endocrine therapy alone for patients with ER-positive, HER2-negative, node-negative breast cancer and an intermediate RS (07:00) Clinical utility of the 21-gene and 70-gene assays (12:29) Benefit with the addition of ovarian function suppression to endocrine therapy for premenopausal women with ER-positive breast cancer at high risk for recurrence (14:11) Approach to assessing the adequacy of ovarian function suppression in premenopausal patients receiving aromatase inhibition (17:01) Significance of clinical risk category in prognosis and in the prediction of chemotherapy benefit by age and RS in the TAILORx trial (19:04) Use of adjuvant bone-modifying agents to reduce the risk of aromatase inhibitor-associated bone loss and fracture (24:51) Role of the 21-gene assay RS in guiding neoadjuvant therapy decision-making for ER-positive, HER2-negative localized breast cancer (27:39) Mechanism of action, efficacy and tolerability of CDK4/6 inhibitors for ER-positive, HER2-negative metastatic breast cancer (31:33) Investigation of CDK4/6 inhibitors alone or in combination with endocrine therapy in the neoadjuvant and adjuvant settings (36:00) Case: A postmenopausal woman in her mid-50s with Grade I, ER-positive, PR-negative, HER2-negative infiltrating ductal carcinoma (IDC) with 1 positive node and a RS of 20 receives an aromatase inhibitor and denosumab (39:49) Approach to the selection of adjuvant endocrine therapy; management of aromatase inhibitor-associated arthralgias (43:33) Clinical and genomic risk to guide the use of adjuvant therapy for breast cancer (46:22) Prospective data with and ongoing evaluation of the 21-gene and 70-gene assays for patients with node-positive disease (49:23) Results from the Phase III KATHERINE study evaluating adjuvant T-DM1 versus trastuzumab for patients with HER2-positive localized breast cancer and residual disease after neoadjuvant treatment (54:20) Rationale for the design and entry criteria of the KATHERINE study (58:18) Mechanism of action, activity and tolerability of antibody-drug conjugates (1:02:46) Second opinion: Therapeutic options for a patient in her mid-40s with recurrent, locally advanced, ER/PR-positive, HER2-positive breast cancer (1:06:23) Clinical implications of the KATHERINE trial results (1:14:53) CME information and select publications

#069_ESMO 2019 | Câncer de Mama_KEYNOTE-522, KATE2 e MONARCH-2_Dra. Heather McArthur

MOC Brasil

Play Episode Listen Later Oct 29, 2019 2:25

ra. Heather McArthur destaca importantes estudos em câncer de mama: o Keynote-522 que demonstrou que a adição de pembrolizumabe à quimioterapia neoadjuvante e aumentou significativamente a taxa de resposta completa em pacientes com câncer de mama triplo-negativo em estágio inicial, o KATE2, um estudo de fase II que sugere um possível benefício de sobrevida global na adição de atezolizumabe ao T-DM1 em câncer de mama avançada HER-2 positivo, sendo necessário um estudo mais aprofundados de fase III, e o MONARCH-2 com dados de sobrevida global no tratamento com abemaciclibe + fulvestranto em pacientes com câncer de mama avançado HER-2.

mama keynote monarch mcarthur esmo t dm1

Jornal da USP no Ar – Medicina #15: Novas linhas de tratamento para asma grave e câncer agressivo de mama

Play Episode Listen Later Sep 27, 2019 32:46

No Brasil, estima-se que a prevalência de asma seja em torno de 10% da população, sendo que os casos de asma grave estão abaixo de 5% do total. Em 2008, a asma foi a terceira causa de internação hospitalar pelo SUS, com cerca de 300 mil hospitalizações ao ano. O Ministério da Saúde abriu consulta pública para avaliar a incorporação do medicamento omalizumabe. Ele é indicado para tratamento da asma alérgica grave em pacientes que não conseguiram o controle da doença, apesar do tratamento preconizado. O Jornal da USP no Ar conversou com o doutor Rafael Stelmach, da Divisão de Pneumologia do Instituto do Coração (Incor) do Hospital das Clínicas (HC) da Faculdade de Medicina (FM) da USP, chefe do Ambulatório de Asma do Incor e embaixador da Iniciativa Global para Asma (Gina) no Brasil. Stelmach esclarece que o omalizumabe já é utilizado no Brasil há mais de 15 anos. A utilização do medicamento acontece em grande parte na rede privada. Na rede pública, o remédio já foi obtido através de ações judiciais ou administrativas junto à Secretaria Estadual de Saúde de São Paulo. No Ambulatório de Asma do Incor, o omalizumabe faz parte da medicação padrão há quase seis anos, mesmo não sendo disponibilizado via SUS. Diferente do que se imagina, a morte por asma não é rara. “Nos últimos anos, temos de três a seis mortes por asma todos os dias no mundo”, destaca o embaixador da Gina no Brasil. “São mortes provocadas pelo não cuidado; o tratamento é muito eficaz, mas sem ele pode ocorrer um fechamento agudo das vias aéreas, impossibilitando a respiração do paciente.” Outro tema do episódio de hoje, o câncer é uma doença que assusta e preocupa por ter tratamentos intensos e com efeitos colaterais fortes, como a queda de cabelo. Um novo tratamento quimioterápico chamado T-DM1 para o câncer de mama agressivo apresenta menos efeitos adversos e tem comprovação de eficácia, com redução de 50% do risco de recorrência e morte em pacientes. O Jornal da USP no Ar conversa com a doutora Maria Del Pilar Estevez Diz, chefe da Oncologia Clínica do Instituto do Câncer do Estado de São Paulo (Icesp), sobre o assunto. Segundo o Instituto Nacional de Câncer (Inca), cerca de 60 mil novos casos de tumores de mama são diagnosticados por ano no Brasil. O tipo HER2-positivo é uma forma particularmente agressiva da doença – com alta taxa de proliferação, ele afeta entre 15% e 20% das mulheres. “Antes de haver um tratamento específico para esse grupo de pacientes, tínhamos uma taxa de mortalidade bastante elevada”, discorre a doutora Del Pilar, e avança: “Há mais de dez anos foi desenvolvido um anticorpo monoclonal, chamado Trastuzumab, para o tratamento do HER-2”. Com isso, além do tratamento convencional – cirurgia, quimioterapia, radioterapia –, as pacientes começaram a receber o Trastuzumab, resultando em um aumento da expectativa de vida. A Agência Nacional de Vigilância Sanitária (Anvisa) aprovou o uso do T-DM-1 em pacientes com câncer HER2-positivo, em estágio inicial, que apresentam doença residual invasiva depois de terapia prévia à cirurgia. Antes, o medicamento era exclusivo para paciente em estado de metástase. Não se esqueça, essas e outras entrevistas você acompanha de segunda a sexta, das 7h30 a 9h30, na Rádio USP 93,7 em São Paulo, e 107,9 em Ribeirão Preto e streaming. Você pode baixar o podcast e ouvir a qualquer hora, acessando jornal.usp.br ou utilizar seu agregador de podcast preferido, no Spotify, iTunes e CastBox. Apresentação e produção: Roxane Ré Edição de Som: Cido Tavares

Breast Cancer | Ian E Krop, MD, PhD

Play Episode Listen Later Sep 9, 2019 74:52

Breast Cancer Update, Issue 2, 2019 — Part 1: Our interview with Dr Krop highlights the following topics as well as cases from his practice: Case: A patient in her late 40s with ER-positive, HER2-positive, node-positive breast cancer experiences a near complete response after treatment with neoadjuvant doxorubicin, cyclophosphamide, paclitaxel, trastuzumab and pertuzumab (AC-THP) (00:00) Choice of neoadjuvant chemotherapy for patients with HER2-positive breast cancer (01:43) Pertuzumab toxicity with or without chemotherapy (05:25) Management of the axilla in patients with clinically node-positive breast cancer who achieve a pathologic complete response to neoadjuvant systemic therapy (07:42) Design and results from the Phase III KATHERINE study evaluating adjuvant T-DM1 versus trastuzumab for patients with HER2-positive early breast cancer and residual disease after neoadjuvant treatment (09:46) Perspective on the benefits and risks of T-DM1/pertuzumab versus T-DM1 alone as adjuvant therapy (13:04) Benefit of T-DM1 compared to trastuzumab irrespective of the extent of residual disease at surgery in the KATHERINE trial (14:45) Clinical implications of the KATHERINE trial results (17:48) Results from the Phase III KRISTINE study evaluating neoadjuvant docetaxel, carboplatin, trastuzumab and pertuzumab (TCHP) versus T-DM1 and pertuzumab for HER2-positive breast cancer (19:42) Use of cold caps to reduce the risk of alopecia with chemotherapy (23:53) Side-effect profile of T-DM1 in the adjuvant KATHERINE trial (25:27) Perspective on the use of neratinib in the post-(neo)adjuvant and metastatic settings (29:42) APHINITY: Phase III study evaluating adjuvant pertuzumab in combination with trastuzumab and chemotherapy for HER2-positive early breast cancer (34:08) Biomarker analysis of the APHINITY trial: Genomic correlates of response to adjuvant pertuzumab with trastuzumab for HER2-positive breast cancer (36:15) Emerging data with immune checkpoint inhibitors in combination with HER2-targeted therapy for HER2-positive breast cancer (40:22) HER2 heterogeneity as a predictor of response to neoadjuvant T-DM1 and pertuzumab: Results from a prospective clinical trial (42:09) Changes in HER2 status during disease progression (45:50) Case: A woman in her early 60s with de novo ER-positive, HER2-positive metastatic breast cancer (mBC) experiences disease progression in the brain during treatment with T-DM1 (47:35) Activity of T-DM1 in patients with brain metastases (48:58) Efficacy and tolerability of tucatinib for HER2-positive mBC; ongoing Phase II HER2CLIMB study evaluating tucatinib versus placebo, each in combination with capecitabine and trastuzumab (52:41) Emerging data with neratinib and capecitabine for patients with HER2-positive breast cancer and brain metastases (55:23) Response to CDK4/6 inhibitors in patients with ER-positive, HER2-positive mBC (58:38) Case: A woman in her early 30s with HER2-positive mBC receives trastuzumab deruxtecan on a clinical trial after experiencing disease progression on multiple lines of therapy (1:02:42) Results of a Phase I trial of trastuzumab deruxtecan for patients with advanced HER2-positive breast cancer previously treated with T-DM1 (1:05:20) Benefits and risks of trastuzumab deruxtecan for advanced HER2-positive breast cancer (1:06:31) Response to trastuzumab deruxtecan in patients with breast cancer and low HER2 expression (1:09:03) Other novel agents and approaches under evaluation for HER2-positive breast cancer (1:13:15) CME information and select publications

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Breast Cancer | Sara Hurvitz, MD

Play Episode Listen Later Sep 9, 2019 55:29

Breast Cancer Update, Issue 2, 2019 — Part 1: Our interview with Dr Hurvitz highlights the following topics as well as cases from her practice: Optimal duration of adjuvant trastuzumab; analysis of the results from the Phase III PERSEPHONE and PHARE studies (00:00) Perspective on the role of trastuzumab biosimilar agents in the management of HER2-positive breast cancer (04:43) Benefits and risks of anthracycline-containing and anthracycline-free neoadjuvant regimens for patients with HER2-positive disease (08:03) Comparison of paclitaxel/trastuzumab/pertuzumab to TCHP in the neoadjuvant setting (11:17) Activity of pertuzumab in combination with T-DM1 in the (neo)adjuvant and metastatic settings (13:21) Case: A woman in her mid-40s with ER-positive, HER2-positive breast cancer attains a good response to neoadjuvant T-DM1/pertuzumab on the KRISTINE study (16:15) KRISTINE: A Phase III study of neoadjuvant TCHP versus T-DM1/pertuzumab for HER2-positive breast cancer (19:05) Primary analysis of SOPHIA: A Phase III study of the novel anti-HER2 antibody margetuximab and chemotherapy versus trastuzumab and chemotherapy for pretreated HER2-positive mBC (22:58) Case: A woman in her late 40s with HER2-positive mBC receives trastuzumab deruxtecan on a clinical trial after experiencing disease progression on tucatinib (27:17) Ongoing Phase II HER2CLIMB study investigating tucatinib with capecitabine and trastuzumab for advanced HER2-positive breast cancer (31:06) Emerging data with trastuzumab deruxtecan for patients with advanced HER2-positive breast cancer who received prior treatment with T-DM1 (33:32) Potential clinical role of trastuzumab deruxtecan (37:10) Preemptive measures to mitigate nausea and the risk of pneumonitis associated with trastuzumab deruxtecan (38:45) Case: A woman in her early 40s with HER2-positive mBC experiences a prolonged remission with trastuzumab and lapatinib in combination with chemotherapy (41:22) Predictors of benefit with HER2-targeted therapy; risk of recurrence for patients with HER2-positive breast cancer (47:05) Role of CDK4/6 inhibitors for patients with ER-positive, HER2-positive mBC; activity of PI3K inhibitors in patients with PIK3CA mutations (50:30) Neratinib and capecitabine versus lapatinib and capecitabine for HER2-positive mBC previously treated with HER2-directed therapy: Findings from the Phase III NALA trial (52:40) CME information and select publications

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Dr. Priya Rastogi Discusses How the KATHERINE Study Will Inform Early Breast Cancer Care

Play Episode Listen Later Jul 18, 2019 7:13

Welcome to the ASCO Daily News podcast. I'm Lauren Davis. And joining me today is Dr. Priya Rastogi, who specializes in the diagnosis, treatment, and prevention of breast cancer at the Magee-Womens Hospital of the University of Pittsburgh Medical Center. And she's also the senior associate medical director for the NSABP Foundation. Today, we're discussing the topic of recurrence among patients with HER2 positive breast cancer, progress and providing more aggressive therapies in early breast cancer for those patients whose cancer is more likely to recur. Namely those with residual invasive disease following taxane and trastuzumab based treatment given before surgery is our area of focus. Dr. Rastogi, welcome to the podcast. Hi, Lauren, happy to discuss the exciting results from the KATHERINE study. We're glad you're here. So as an investigator of the KATHERINE study, I'd like to hear a little bit about some of the findings. So I understand that the study showed that T-DM1 reduced the risk of disease recurring by half compared with trastuzumab in HER2 positive early breast cancer. Yes. So in terms of background information, patients with HER2 positive early breast cancer receiving neoadjuvant treatment had favorable outcomes if they achieve a pathological complete response. But patients with residual breast cancer in the surgical specimen have a higher risk of recurrence. And so that's some of the rationale of how the KATHERINE study was set up. The KATHERINE trial was an open label study with 1,486 patients with HER2 positive early stage breast cancer who received neoadjuvant chemotherapy plus HER2 targeted therapy that included a taxane and trastuzumab followed by surgery. And then all these patients had residual invasive disease in the breast and/or actually in lymph nodes. So within 12 weeks of surgery, patients were assigned to either T-DM1 or to trastuzumab. And as you mentioned, the primary endpoint was IDFS. And so in the KATHERINE study, T-DM1 significantly reduced the risk of developing an invasive disease free survival event by three years by 50%. And this corresponds to an absolute improvement in three year invasive disease free survival of 11 percentage points. So this is really exciting. So the invasive disease free survival rate was 77% with trastuzumab, and it increased to 88.3% with T-DM1. So the KATHERINE trial demonstrates that neoadjuvant therapy can be used to identify patients at increased risk for recurrence based on less than optimal response to standard neoadjuvant therapies who can then benefit by switching to T-DM1. The overall survival analysis has not yet matured. We had a total of 98 deaths, 56 deaths with trastuzumab and 42 with T-DM1 for a hazard rate of 0.7. So clearly, this study will need more follow up. So the FDA approved T-DM1 as adjuvant treatment for this patient population. Do patients have immediate access? Yes, so this is also exciting news that the US FDA approved T-DM1 for the adjuvant treatment in patients with HER2 positive early stage breast cancer with residual invasive disease after neoadjuvant taxane trastuzumab based therapy. The results and approval form the foundation of a new standard of care in patients in this setting. And this should lead to access and availability for patients. Patients should discuss with their physicians and their insurance providers. That's exciting. So one of the things we always think about are side effects. What should specialists tell their patients? Yeah, so as you mentioned, side effects are very important. So the safety profile of T-DM1 is as expected from what has been seen in the metastatic setting in the use of T-DM1. The main adverse events in our study was a decrease in platelet counts, an increase in sensory neuropathy and liver enzymes compared to trastuzumab. Although, these side effects are mostly mild. Fatigue and nausea were also greater. But they were manageable and reversible. So the side effect profile is similar to what had been seen in the metastatic setting and the efficacy is fantastic for this drug. Oh, that's great. Were there any surprises in the results? So the analysis by the subgroups demonstrated that there was a benefit across all the key subgroups. So for example, patients with operable or inoperable cancers at presentation, hormone receptor positive or hormone receptor negative, post neoadjuvant positive or negative nodes, and even patients with very small residual disease all had a tremendous benefit from T-DM1. So this is also very exciting that all the subgroups benefited. So what do you think is on the horizon for breast cancer studies? That is also a very important question. So immunotherapy is a type of cancer treatment which also helps the immune system fight cancer. And immunotherapy has been approved in other cancers. One type of these drugs is atezolizumab, which belongs to a class of drugs known as the checkpoint inhibitors. By inhibiting the checkpoint proteins such as PD-L1 and PD-1, these drugs enhance the ability for the immune cells to attack cancer cells. So recently, the FDA approved atezolizumab in combination with chemotherapy for the initial treatment of women for advanced triple negative breast cancer with PD-L1 positive tumors. So the NSABP Foundation in collaboration with the German Breast Group is conducting a phase III study, it's NSABP B59 [INAUDIBLE], for patients with early stage high risk triple negative breast cancer. And so this trial is evaluating neoadjuvant chemotherapy with atezolizumab or a placebo followed by surgery. Patients then receive an additional six months of either atezo or placebo after surgery. And the co-primary end points are pathological complete response and event free survival. And this study will address if neoadjuvant atezolizumab in combination with neoadjuvant chemotherapy followed by adjuvant atezolizumab will improve outcomes in this high risk patient population. That's fantastic. It sounds like there's a lot of things to look forward to. Again, today, my guest has been Dr. Rastogi. Thank you so much for being on our podcast today. It has been a privilege. And thank you for inviting me to talk about the KATHERINE study. And to our listeners, thank you for tuning in to the ASCO Daily News podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple Podcast.

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Breast Cancer | Interactive Tumor Panel: Clinical Investigators Discuss Emerging Research and Actual Cases of Patients with Breast Cancer

Play Episode Listen Later Jun 28, 2019 152:18

Proceedings from a CME symposium held at the 2019 ASCO Annual Meeting. Featuring perspectives from Prof Fabrice André and Drs Virginia Kaklamani, Mark D Pegram, Hope S Rugo, Sara M Tolaney and Tiffany A Traina: Introduction Program overview: Dr Love (00:00) Available and Emerging Data Sets Shaping the Management of Localized HER2-Positive Breast Cancer (BC) Case (Dr Rugo): A woman in her mid-40s with ER/PR-negative, HER2-positive BC who received neoadjuvant TCHP and experienced a pathologic complete response (3:57) Case (Dr Rugo): A woman in her mid-50s with an ER-positive, HER2-positive infiltrating lobular carcinoma who received neoadjuvant chemotherapy/anti-HER2 therapy, had residual disease at surgery and initiated treatment with T-DM1 (6:39) Case (Dr Rugo): A woman in her early 40s with an ER-positive, HER2-positive IDC who received postadjuvant neratinib (11:42) Faculty Presentation: Dr Rugo (14:18) Use of Genomic Classifiers in Clinical Decision-Making for Patients with ER-Positive Early BC Case (Dr Kaklamani): A postmenopausal woman in her late 50s with an ER/PR-positive, HER2-negative, node-negative IDC and a 21-gene Recurrence Score® of 24 (38:46) Case (Dr Kaklamani): A postmenopausal woman in her mid-50s with an ER/PR-positive, HER2-negative IDC with 2 positive nodes and a 21-gene Recurrence Score of 21 (41:47) Faculty Presentation: Dr Kaklamani (48:39) Selection and Sequence of Therapy for ER-Positive, HER2-Negative Metastatic BC (mBC); Novel Agents and Strategies Under Evaluation in ER-Positive Disease Case (Prof André): A postmenopausal woman in her mid-50s who presented with ER/PR-positive, HER2-negative mBC approximately 2 years after the completion of adjuvant letrozole (1:07:13) Case (Prof André): A woman in her mid-70s with de novo ER/PR-positive, HER2-negative mBC with extensive liver involvement who received palbociclib/letrozole (1:10:03) Faculty Presentation: Prof André (1:11:05) Immunotherapy as a Rational Therapeutic Strategy in BC Case (Dr Tolaney): A woman in her early 60s with metastatic triple-negative BC (TNBC) who received atezolizumab/nab paclitaxel and remains NED 4 years later (1:28:14) Case (Dr Tolaney): A woman in her mid-60s with heavily pretreated TNBC who experienced a complete response to pembrolizumab but developed treatment-related diabetes and hypothyroidism (1:31:00) Faculty Presentation: Dr Tolaney (1:32:49) Protocol and Off-Protocol Decision-Making for Patients with HER2-Positive mBC Case (Dr Pegram): A woman in her mid-60s with widespread ER-negative, HER2-positive mBC who received tucatinib/capecitabine/trastuzumab on a clinical trial (1:46:01) Faculty Presentation: Dr Pegram (1:47:28) Role of PARP Inhibitors, Novel Agents in mBC; Male Breast Cancer Case (Dr Traina): A woman in her early 60s with metastatic TNBC and a germline BRCA2 mutation who received olaparib monotherapy and achieved a complete response (2:11:31) Case (Dr Traina): A woman in her early 70s with metastatic androgen receptor-positive TNBC who received an investigational antiandrogen on a clinical trial (2:13:12) Case (Dr Traina): A man in his early 60s with ER/PR-positive, HER2-negative mBC and a germline BRCA2 mutation (2:16:16) Faculty Presentation: Dr Traina (2:18:32) Select publications

Oncology Grand Rounds Series: Part 5 — Breast Cancer

Play Episode Listen Later Jun 25, 2019 117:17

Video proceedings from the fifth in a series of 6 integrated symposia held at the 2019 ONS Annual Congress. Featuring perspectives from Dr Erika Hamilton, Ms Elizabeth O'Reilly, Dr Hope S Rugo and Ms Gretchen Santos: Introduction (00:00) Program overview: Dr Love HER2-Positive Localized and Metastatic Breast Cancer (BC) (2:16) Case (Ms O'Reilly): A woman in her late 40s with ER-positive, HER2-positive Stage IIIB inflammatory BC who received neoadjuvant treatment, had significant residual disease at surgery and began adjuvant T-DM1 (9:04) Case (Ms Santos): A woman in her early 60s with ER-negative, HER2-positive BC who began 1 year of adjuvant trastuzumab/pertuzumab after mastectomy but was switched to T-DM1 (12:31) Case (Ms Santos): A woman in her early 40s with ER-positive, HER2-positive BC who received postadjuvant neratinib on the CONTROL study (38:38) Case (Ms O'Reilly): A woman in her early 60s initially diagnosed with ER-positive, HER2-negative BC presents with ER-positive, HER2-positive metastatic disease to the bone, liver and brain (43:41) ER-Positive, HER2-Negative Metastatic Disease (55:50) Case (Ms Santos): A premenopausal woman in her early 50s with widespread ER/PR-positive, HER2-negative metastatic BC to the bone who underwent ovarian ablation and received palbociclib/letrozole (1:5:38) Case (Ms O'Reilly): A woman in her early 50s with ER-positive metastatic BC who received multiple lines of systemic treatment, including abemaciclib monotherapy (1:15:53) Triple-Negative Metastatic BC (1:31:31) Case (Ms Santos): A woman in her mid-30s with metastatic triple-negative BC who experienced a good response to pembrolizumab (1:37:46) Select publications

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May Approvals, More Questions

OncoPharm

Play Episode Listen Later May 16, 2019 13:00

Running through updated FDA approvals from this month (ivosidenib, T-DM1, ramucirumab, avelumab/axitinib, & venetoclax/obinutuzumab) and how these approvals raise more questions.

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Breast | Oncology Today with Dr Neil Love: Breast Cancer Edition