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Dr. Monty Pal and Dr. Vamsi Velcheti discuss the evolving treatment landscape in EGFR-mutated non-small cell lung cancer, including landmark trials like FLAURA2, novel drug therapies, and the growing importance of ctDNA and MRD testing. TRANSCRIPT Dr. Monty Pal: Hello, and welcome to the ASCO Daily News Podcast. I'm your host, Dr. Monty Pal. I'm a medical oncologist and professor and vice chair of academic affairs at the City of Hope Comprehensive Cancer Center in Los Angeles. Today, I'm truly delighted to introduce Dr. Vamsi Velcheti, who's a professor of medicine and the chief of hematology-oncology at the Mayo Clinic in Jacksonville, Florida. We'll be discussing the expanding treatment landscape in EGFR-positive lung cancer and how to navigate the challenges of balancing treatment efficacy, toxicity, and patient quality of life in the EGFR-positive space.  Just FYI, our full disclosures are available in the transcript of this episode.  Vamsi, it's so great to have you on the podcast. Thank you so much for being here. Dr. Vamsi Velcheti: Thank you, Monty. It's a pleasure to be here with you. It's a really exciting topic and there are a lot of updates in the EGFR space. Dr. Monty Pal: So, I'm going to need your help with this because I'll be honest with you, I see very little lung cancer, if any, in my practice. I'm pretty much exclusively kidney cancer these days. I'm coming on 20 years at City of Hope now, and I still remember when trials like ECOG 1599 were presented with, you know, platinum doublets. And, of course, the field has changed a lot since then. But tell us a little bit about the first-line landscape, and I think just for the sake of time, we're going to stick with EGFR-positive disease here. What does it look like these days? Dr. Vamsi Velcheti: Monty, the foundation of care remains the third-generation EGFR inhibitors. These are selective EGFR inhibitors, like osimertinib. We've had an evolution of the development of these TKIs. Like, you know, we had the first-generation, second-generation, not-so-selective EGFR inhibitors. Now we have mutant-selective EGFR inhibitors in the clinic, and they're doing a really good job. And these are quite effective in patients who have classical activating mutations. But the reality is that these have not been transformative. These agents have fundamentally changed the response patterns, excellent CNS penetration, and very good tolerability profile. However, we don't see a lot of durability in terms of the response. So, what's different today is now there have been several trials in combination with these third-generation EGFR inhibitors that have really laid the foundation of how we kind of think about EGFR-positive disease. At the high level, there are a lot of challenges to selecting the patients for these combination-based modalities. I'm assuming we'll be talking more about these different trials and different approaches. Some of these combination-based strategies have really moved the needle in terms of improving overall survival and really improving long-term outcomes and durability in our patients. Dr. Monty Pal: And we are going to get into the weeds on this in just a moment. But I did kick off this podcast talking about chemotherapy, ECOG 1599. It does seem as though chemotherapy is still a component of management in advanced non-small cell lung cancer. So, can you tell us about, perhaps first, you mentioned osimertinib, you know, some of these next-generation EGFR inhibitors. Tell us about the role of chemo plus osimertinib. Dr. Vamsi Velcheti: That's exactly where I was going with the combination-based strategies. You know, we first started off with our earlier trials in the EGFR space evaluating the question of, are targeted therapies, are these highly effective, third-generation, EGFR-selective inhibitors, superior to platinum-doublet chemotherapy? And we've had multiple trials demonstrating that, like the FLAURA trial and in the past with second-generation EGFR inhibitors like erlotinib and gefitinib and afatinib. So, we know that these TKIs actually perform better than platinum-doublet chemotherapy. Now, we have a large, global, phase 3 trial data from the FLAURA2 trial, which looks at the question, "Hey, you know, osimertinib is better than chemotherapy, platinum-doublet chemotherapy. Can we do even better by combining osimertinib with platinum-doublet chemotherapy?" So, FLAURA2 answered that question. This is a large, phase 3 trial, and it's a positive trial with improved durability of disease control and improving overall survival with combination with chemotherapy. So, it's a very important and landmark trial, and essentially combining osimertinib with a platinum-based chemotherapy improved responses, deepened responses, and improved overall survival and really changing the disease trajectory. And this strategy is definitely compelling, especially in patients who have certain clinical high-risk features like, you know, patients who have high disease burden or patients who are sometimes having rapid disease progression early on osimertinib, especially with patients who have a lot of visceral disease burden. So, intensifying treatments up front could alter the natural trajectory of the disease. Dr. Monty Pal: So, you sort of alluded to this in that last part there, but is that kind of how you in clinical practice select? Is it based on, you know, visceral involvement? Is it based on rapidity of disease where you think about adding chemotherapy to osimertinib? Maybe you can give us the corollary. Which patients do you just use osimertinib alone in, for instance? Dr. Vamsi Velcheti: Definitely, there are some patients who have low disease burden and they have the classical mutations, like an exon 19 deletion. And these patients, especially if they don't have a lot of disease burden, they don't have CNS involvement, there may be a subset of patients who could just do fine on osimertinib of course, with close monitoring of the disease. I guess we'll get into that later, how do we do that with either ctDNA or like closer imaging or both. So, there may be some opportunity to kind of escalate patients' treatments based on certain clinical characteristics or radiographic characteristics or certain biological characteristics informed by ctDNA or other approaches. Dr. Monty Pal: No, that's interesting. And you're right, we will chat about ctDNA in just a bit. But before we get there, I think one of the big agents that has really sort of come to the fore in advanced non-small cell lung cancer is amivantamab. I've heard a lot about this in the context of even kidney cancer because in certain subsets, I'm interested in MET-directed therapies and so forth, right? So maybe tell us a little bit about the mechanism of amivantamab first, and then maybe tell us about this pivotal MARIPOSA trial where it's combined with lazertinib. Dr. Vamsi Velcheti: So, the MARIPOSA trial compared lazertinib alone with amivantamab plus lazertinib. And this trial demonstrated overall survival advantage, and there were key differences in terms of tolerability and the safety of amivantamab, which is an EGFR and MET bispecific, and there were certain kind of unique toxicity profiles that make it a little different than the intensification approach with chemotherapy through the FLAURA2 trial. So, there's a trade-off in terms of the toxicity profile. It's a different agent and a different management protocol in terms of dermatological toxicity management that clinicians need to be comfortable with. And also, there are certain unique issues in terms of amivantamab; there's a higher rate of infusion-related reactions, there's an increased risk for edema and VTEs because of amivantamab. Certainly a different toxicity profile, different management paradigm there in terms of longitudinal care of these patients requiring dermatological care and like, you know, close monitoring and prophylaxis VTEs. But having said that, definitely it's a different strategy, and it kind of changes the biology and the natural history of the cancers, and we do see some durability of responses that we see with the MARIPOSA. So, it's certainly a great alternative, at least for some patients. Dr. Monty Pal: That was a great overview of MARIPOSA. Now comes the really difficult question, which is, how do you choose between the two? You have these two great options, right, for EGFR-positive patients. You've already highlighted some of the distinctions in terms of toxicity. I think the audience is well aware of the side effects of chemo-doublet, perhaps even the EGFR-based therapies. Amivantamab is quite new. Give us a sense of how you in clinical practice decide between the two potential options here. Dr. Vamsi Velcheti: Yeah, I think that's the big challenge. I think these are two independent strategies that have evolved through the phase 3, and both of them have demonstrated overall survival benefit. So, the way I think about this is in three dimensions, right? Like, the disease biology, the patient priorities, and feasibility of care delivery. So, when I talk about the disease biology, you know, the mechanism is very different, and MET is a very dominant driver of disease in EGFR-altered patients and it's a significant mechanism of resistance, acquired resistance to TKIs. So, certainly I think there's a patient population that could benefit from a MET-directed therapy up front. However, we don't have great data to kind of really demonstrate how using amivantamab in the front line is going to change that. And are there like perhaps like some patients who we could identify who would benefit from such a strategy? Very recently, there have been some approvals in the second-line setting in lung cancer, not in the EGFR space, but like in generally in lung cancer, with the MET ADCs, and those drugs are approved with a companion diagnostic, which requires MET IHC testing. So, what has happened, at least in large academic practices and also I think in the community now, they have been checking for MET IHC expression more routinely in lung cancer. What we have been doing in our institution is we have been doing MET IHC as a reflex for all patients with EGFR, not just EGFR, but all non-small cell lung cancer patients. What that has done is now, like, we have been increasingly testing patients with EGFR for MET. And there's clearly a subset of patients who have de novo MET expression and a high MET expression. And those patients, I've been kind of like preferentially treating them with the MARIPOSA regimen. But again, I have to caution the audience that we still don't have data that MET IHC is going to help us make those decisions, whether it's better than like a FLAURA2 regimen. But however, in the second-line setting in the CHRYSALIS trial, we know that MET is a very powerful predictor of response to amivantamab. We really need more data there, but that's what I have been doing in my practice. But also, there's a lot of patient preference here. Like, there are some patients who don't want chemotherapy, and they want a non-chemotherapy approach. So, certainly there are some patients who prefer to have amivantamab. And now with the amivantamab, the subcutaneous version, the infusion reactions and the logistics of actual administration of amivantamab are more favorable with the subcutaneous approval. So, those are some of the elements that we need to take into account. Dr. Monty Pal: Well, I want to hone in on that because this subcutaneous administration route has been a big debate that I've seen on social media. Tell us, how much easier does it actually make the amivantamab experience? Does it cut down on the rash? Is it just infusion reactions? What's been your clinical experience? Vamsi Velcheti, MD: So, the subcutaneous administration of amivantamab has definitely improved the infusion reaction issue. Very rarely patients have infusion reaction now with the subcutaneous injections. And also, the infusion time is much, much shorter. Like we don't need a lot of infusion time, which is sometimes a challenge in busy infusion clinics. We need to take that into account. As far as the impact of the subcutaneous formulation on dermatological toxicity, we haven't really seen significant difference in terms of the intensity or rates of dermatological toxicity with subcutaneous. The benefits are really with the infusion reaction, the ease of administration. And interestingly, in the PALOMA trial, it also seems to be, even though this was not the primary endpoint of the study, there seems to be some suggestion that the subcutaneous amivantamab seems to have improved OS compared to the IV amivantamab. We don't really understand why, but that's a finding from the trial that's very intriguing. Dr. Monty Pal: That is really fascinating. I'm kind of curious to see how that's going to pan out. I'm going to shift gears a little bit here. And, you know, as we sort of close, I wanted to talk a little bit about biomarkers. I mean, this is obviously not a lung cancer-specific issue. It's something we think about across the board. But what I will say is that there are certain commonalities, and in bladder cancer, we think a lot now about ctDNA. But you've been way ahead of the game in lung cancer. Tell us how you guys use ctDNA, maybe both from the standpoint of monitoring for mutational status, but if you can, maybe offer some insights into some of these new MRD tests that are available too. Dr. Vamsi Velcheti: Yeah, it's rapidly evolving. Certainly, I think in the lung cancer space, you know, this has really kicked off in the lung cancer space with incorporating ctDNA into the workflow. Of course, you know, like baseline evaluation, we still kind of heavily rely on tissue genomic sequencing. But as you know, with targeted therapy, a lot of these patients have disease that evolves over time, and changes in terms of mutational pattern driving acquired resistance is a major issue across different molecular subtypes. And especially so in EGFR, when there are certain actionable opportunities associated with that transformation. So, we need to kind of have like a longitudinal snapshot of how we monitor these patients. So, the ctDNA has come to be like a tool that has now come to the forefront of clinical workflow, and almost all my patients who are having disease progression have ctDNA for kind of evaluating for resistance and informing treatment decisions, especially in EGFR. But having said that, there are a lot of challenges in terms of using ctDNA as a tool for monitoring. There are a lot of different types of assays and different platforms, and being able to use this as a quantitative tool that would be used along with the CT scans that we routinely use in clinical practice has been a challenge. And I think I would love to hear your perspectives as well, Monty, about how you're thinking about that in bladder and other disease contexts. But having said that, I think there's a lot of opportunity to incorporate ctDNA and MRD assays into clinical decision-making. Right now, in terms of clinical trials and clinical development, there have been some very interesting trials that are currently ongoing, especially in the EGFR space. We know that patients who clear ctDNA, based on some retrospective data and also like some retrospective-prospective data from trials that have already read out, that patients who clear ctDNA early with target therapy tend to do much better. They have a longer durability of response. There may be a subset of patients who have, even though they're having radiographic response, they have persistent ctDNA after a certain time point of initiation of targeted therapy. Those patients may require escalation of therapy. We don't yet know. I can't recommend that as a standard right now because we don't have clinical evidence to support that. But however, some of the clinical trials, like the ELIOS trial that's being done right now, that's actually completed enrollment, we'll hopefully see the results very soon. So, there is an emerging thought that instead of intensifying treatment for all patients with EGFR, there may be a population that may be just fine with frontline osimertinib monotherapy and introducing the intensification strategy at the time of emergence of MRD or progression on ctDNA before radiographic progression. So, there are a lot of adaptive molecular response criteria that we are kind of exploring in clinical trials that could inform how the future is going to look like for EGFR and other perhaps targeted therapies as well. So, it's fascinating, and I think there's a lot of opportunity there. Dr. Monty Pal: You know, you asked for my perspective. I actually think that what you highlighted there is the most interesting opportunity for ctDNA: the ability to de-escalate therapy. In terms of drug development, we've done so much to bring new therapies to patients, and now it's a bit of an embarrassment of riches, but the downside is that I feel like we tend to overtreat a lot of patients in the clinic. So, I definitely view MRD, you know, some of these other ctDNA techniques with methylation and so forth that may not be sort of tumor-dependent or bespoke could be incredibly, incredibly helpful. You touched on sort of the future, right, in this last section here with biomarkers. But give us a sense now in terms of novel drug therapies in the EGFR space. What are you most excited about moving forward in 2026 and beyond? Dr. Vamsi Velcheti: Yeah, I think there's a lot going on in this space, and not just this space, but across lung cancer and others as well. Like looking at the next generation of targets for ADCs. And I think a lot of these have to do with…so far in the drug development space, as you know, the improvements in clinical outcomes has been very incremental. So, we really need to make that big leap. And I think the big leap is not going to come from, in my opinion, from the next ADC, but it's going to come from how we tailor treatments and how we monitor disease better and how do we kind of incorporate the next treatment earlier and not wait for the radiographic progression. So, there's a lot of opportunity there to integrate biomarkers and dynamic biomarkers into clinical trial design and incorporating the recent advances in terms of drug design. You know, we have a lot of assets in the EGFR space, the next-generation EGFR inhibitors that are kind of designed with resistance in mind and rational combination, knowing when to introduce those combinations is also equally important. So, there's a lot going on, really exciting times to be in drug development. The one thing that I really hope will come to the forefront in drug development, not just for lung cancer, but all disease groups, is to kind of really be thoughtful about how we incorporate these really cool molecular monitoring tools and creating a composite score with imaging to be able to like really design the next generation of clinical trials. Dr. Monty Pal: You're so spot-on with that. I definitely think that we're getting to this point where, you know, we could think about the next BiTE, the next CAR-T, the next ADC. But, you know, maybe it's time for us to start really honing in on appropriate applications of these drugs, honing in on the right dose and what have you, because I definitely see some issues there.  Vamsi, this has just been terrific. I really want to thank you so much for sharing your fantastic insights with us today on the ASCO Daily News Podcast, and I really appreciate all your efforts to move the field of lung cancer forward. Dr. Vamsi Velcheti: Thanks, Monty. I really enjoyed the conversation. Dr. Monty Pal: Yeah, this was terrific.  And thanks to our listeners as well. If you value the insights that you hear from 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. Monty Pal   @montypal  Dr. Vamsi Velcheti @VamsiVelcheti Follow ASCO on social media:          ASCO on X    ASCO on Bluesky         ASCO on Facebook          ASCO on LinkedIn          Disclosures:       Dr. Monty Pal:      Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview     Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical     Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis   Dr. Vamsi Velcheti:   Honoraria: Galvanize Therapeutics  Consulting or Advisory Role: Bristol-Myers Squibb, Merck, AstraZeneca/MedImmune, GSK, Amgen, Taiho Oncology, Novocure, Regeneron, Takeda, Janssen Oncology, Picture Health Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline

This interview is brought to you in partnership with Eisai and is part of the Journey to Diagnosis series.Eisai: https://www.eisai.com/index.htmlJourney to Diagnosis: https://beingpatient.com/journey-to-diagnosis/Andrew Reid was 56 when he was diagnosed with early-onset Alzheimer's after unexplained changes that affected his work, driving, and daily functioning. He lives with a rare form of the disease called Posterior Cortical Atrophy (PCA), which primarily affects visual processing. Before his diagnosis, Andrew built a career in management and leadership as the founder and CEO of Big Fish Interactive, a leadership training firm focused on guiding organizations through positive change. He's also a gold medalist in the European Dragon Boat Championships. Andrew and his wife, Karina, are committed to sharing their story to educate others about early-onset Alzheimer's, reduce stigma, and amplify the voices of young families facing the disease. Andrew has found strength in an improv acting group and has become a passionate advocate for others living with young-onset Alzheimer's.In this conversation with Being Patient's Mark Niu, Andrew and Karina describe the emotional toll of uncertainty and the importance of getting the right diagnosis. They discuss the realities of living with PCA and strategies to make daily life safer and more manageable, from visual cues in the home to finding new forms of connection through humor, community, and creative outlets like improv. Together, they exemplify how resilience and support can help families keep moving forward even as the disease changes everyday life.------If you loved watching this Live Talk, visit our website to find more of our Alzheimer's coverage and subscribe to our newsletter: https://www.beingpatient.com/Follow Being Patient: Twitter: https://twitter.com/Being_Patient_Instagram: https://www.instagram.com/beingpatientvoices/Facebook: https://www.facebook.com/beingpatientalzheimersLinkedIn: https://www.linkedin.com/company/being-patientBeing Patient is an editorially independent journalism outlet for news and reporting about brain health, cognitive science, and neurodegenerative diseases. In our Live Talk series on Facebook, former Wall Street Journal Editor and founder of Being Patient, Deborah Kan, interviews brain health experts and people living with dementia. Check out our latest Live Talks: https://beingpatient.com/live-talks/

Dr. Pedro Barata and Dr. Kathryn Schmitz discuss evidence-based exercise oncology programs, how to incorporate exercise into cancer care and connect the right patient to the right program, and ultimately build a culture of exercise in oncology. TRANSCRIPT Dr. Pedro Barata: Hello, and welcome to By the Book, a podcast series from ASCO that features compelling perspectives from authors and editors of the ASCO Educational Book. I'm Dr. Pedro Barata. I'm a medical oncologist and a clinical trialist at the University Hospital Seidman Cancer Center and an associate professor of medicine at Case Western Reserve University in Cleveland, Ohio. I'm also happy to serve as a deputy editor for the ASCO Educational Book. Today, we'll be talking about exercise. We have plenty of evidence that exercise benefits symptoms, improves the quality of life of patients, and actually has been shown to reduce risk of recurrence of cancer but also improve survival. And I think that's increasingly clear as data emerges. Today, I'm delighted to be speaking to Dr. Kathryn Schmitz. She's a leading expert on integrating exercise into cancer care. Dr. Schmitz serves as the deputy director of the University of Pittsburgh Hillman Cancer Center and also a professor of hematology-oncology at University of Pittsburgh Medical School. She's the senior author of a fantastic article in the ASCO Educational Book that's titled "Implementation Science as the Secret Sauce for Integrating Exercise Screening and Triage Pathways in Oncology." She also led a really compelling piece that just got published in JCO titled "If Exercise Were a Pill, We'd All Prescribe It to Patients With Cancer. But It's Not" So I'm thrilled to have Dr. Schmitz joining us today and helping us explore evidence-based exercise oncology programs, how to incorporate exercise into cancer care, and also how to connect the right patient to the right program.  So with that, welcome, Dr. Schmitz. Thank you so much for taking the time to chat with us. Dr. Kathryn Schmitz: Thank you for the opportunity. Dr. Pedro Barata: One of the highlights of ASCO last year and practice changing, in my opinion, data out of The New England [Journal of Medicine] is called the CHALLENGE trial. It did provide high level evidence that a structured, supervised exercise program could improve both disease-free survival and overall survival. This is a study in the GI world, but I think it got a lot of attraction and attention beyond the GI world, across solid tumors, really. Could you give us a little brief recap of that trial and what have you seen as being the impact in practices around oncology? Dr. Kathryn Schmitz: So, CHALLENGE was very exciting. Prior to CHALLENGE, there were any number of observational studies that indicated that there was a relationship between being more physically active and reduced recurrence and improved overall survival for colon cancer in particular. You know, notably, in 2006, Jeff Meyerhardt published two papers in the same journal, of the same issue of JCO, showing very, very similar data from two very large studies. And those were studies number five and six in this area. You know, there's a lot of evidence observationally, but we don't generally change clinical practice on the basis of observational data. So, we were all waiting very impatiently for the results of the CHALLENGE trial. And it was very exciting to be in the front row when the results were reported out and to be part of the group with a standing ovation for the authors when it was presented. To summarize, 889 colon cancer patients, stage II and III, were randomized into either a structured exercise program or a health education control comparison group and followed for an average of 7.9 years. And the structured exercise group had a 27% reduced risk of recurrence and a 38% improvement in overall survival. One of the things that's really notable about this is that what we typically expect is that when we go from the observational literature to the clinical trial literature, that we expect effects to go down. We expect to see a larger effect in the observational than in the RCT land, and that did not happen here. We actually see an effect that matches what we've seen in observational literature, which is really, really exciting.  And, you know, one of the reasons why this has been so exciting across not just GI but other cancers is the notable finding of a reduced risk of second primaries. So, they only observed two breast cancer second primaries in the treatment group and 12 in the comparison group. And overall, they reduced the second primaries occurrence, hazard ratio was 0.5, a 50% reduction of second primaries, which is just remarkable. It really got everybody very, very excited. And now the big question, of course, is, all right, how do I do this? How do I make this happen?  The thing to note is that what they did in CHALLENGE is probably not doable in your clinic tomorrow. It's a heavy intervention. The number of touchpoints from staff is extensive, and the amount of time needed from staff for the coaching and supervised exercise is extensive as well. The criteria for getting people into the program required that people go through a series of blood tests and imaging tests that would just simply not be possible for the average community oncologist. So I'm guessing that you're going to ask me some questions about how we do this. Dr. Pedro Barata: Right. That's a fantastic segue. That's exactly right. Walk us through maybe starting by, what does that mean? Dr. Kathryn Schmitz: The first thing to say is I have to go back to the observational literature. And the observational literature shows really compellingly that we have a strong reduction of breast cancer recurrence and mortality from being more physically active, prostate cancer recurrence and mortality, and colon cancer recurrence and mortality. I find it very difficult to believe in this day and age, in our current environment, if you will, that we are ever going to have the equivalent of CHALLENGE for prostate or for breast cancer. There is an ongoing study in prostate that's led by some Australian researchers, but I just don't think that it's likely that we're going to mount something similar for another tumor site. We have tremendous correlative data that indicates that there are a number of biomarkers and biological pathways through which breast, colon, and prostate cancer would be reduced in recurrence if people were more physically active. And so, there is really, from my thinking, very little to state that it would be just a colon cancer effect. And so this is something we probably can enact in more than just the colon cancer community, overall, which is great news, and it makes it easier for us to be able to enact this type of programming. Dr. Pedro Barata: One of the things that comes up perhaps often is, if I were the leader of the cancer center and were to incentivize the different care teams to implement an exercise program at each level: GI team, GU, breast, thoracic, etc. How do we do that? Dr. Kathryn Schmitz: So, I want to give you an analogy. You're a medical oncologist, and you prescribe your patients chemotherapy. Now, just imagine, if you will, what would happen and how likely it would be for your patients to get chemotherapy if there was no chemoinfusion suite. If the chemoinfusion suite disappeared tomorrow and you were to tell your patients, "Go get some chemotherapy," what proportion of those patients do you think would go find all of the equipment necessary and all of the drugs necessary and understand how to dose the chemotherapy for themselves and get that all done? Very few people would do it. So with exercise, why would we be surprised then that our patients don't actually do a whole lot if we just simply tell them to go get some exercise? Exercise is a medicine. It is effective like a medicine. We've shown this through the CHALLENGE trial and many other correlative studies and an ocean of observational data as well. So the question is, how do we build the infrastructure that is necessary in order for your patients to do this? So the very first thing that has to happen is that somebody has to tell the patient to exercise. We currently do not have a culture of exercise in oncology. We do in heart disease. If you ask the average person on the street, "Is exercise good for your heart?" Anybody with an eighth-grade education is going to say, "Yes, of course," because the American Heart Association has done an amazing job telling everybody that exercise is good for your heart. But what has ASCO done, frankly? Can I be that bold? What has ASCO done to tell patients that they should be exercising during and after their cancer treatment? I'm not sure that I know more than a guideline. There is a guideline, and that's great. And the guideline is very helpful, but I'm not sure that patients know that there's a guideline. In fact, I can tell you that patients don't know that there is a guideline. So, you know, making sure that there's a paradigm shift in the country that says exercise is good for patients during and after their cancer treatment is the first step. The second step is getting a medical professional to say something to the patient about the exercise. And I'm very careful with the two words that I just chose: medical professional. I do understand medical oncologists are very busy. I understand that there's a whole lot to say in that 15 minutes when you're with the patient. And so maybe it isn't the medical oncologist. Ideally, it would be, but I get it that there's limited time. So it could be a nurse practitioner, it could be a nurse, there could be a social worker, it could be somebody else on the team that says, "Hey, you know, we want you to do an exercise program. We want to connect you to an exercise program." And then there's what is the program itself? You know, I'm very interested in this happening across the entire country. And so I've been working with the leadership of the Commission on Cancer on the question of, well, how would you do this in community oncology? You know, it's not enough to do it in academic medicine, but how do you do this in community oncology? And you can't expect that every community hospital is going to build a gym for their cancer patients. That is just not reasonable to do. So, we start to try to figure out some phone counseling. Could we give people Fitbits and follow them? Could we use technology to help us? Are there telehealth opportunities for us to do? Are there apps that have been built? In fact, there is a [free] app called Cancer Exercise that's on, you know, all of the platforms and available to patients. So there are programs. I've developed a directory of over 2,000 programs that exist across the country for exercise oncology that patients can find, medical oncologists can find.  So there are a lot of people trying to figure out how best to get the information to medical oncologists and other medical professionals so that they can have an 'easy button' to be able to connect their patients to existing programming so that you don't feel like you have to build a whole new program. Dr. Pedro Barata: If I don't have the resources around me, what would be your advice for the care team or for the providers that might not have that available at their site? Where do they start? Who do they reach out to? Who should they be looking at to get more information on how to set it up? Dr. Kathryn Schmitz: I lead an international consortium called Moving Through Cancer. You can find us at movingthroughcancer.org. That's where you'll find the map of all of the programs across the country and the directory. We actually have a triage tool that sits at the front of the directory that allows people to discern what type of exercise they're safe to do. We do recognize that, you know, the 80-year-old that fell last week doesn't need the same program as the 35-year-old that was playing pickleball the day before diagnosis. So, you know, there are different kinds of programs for people at different levels of acuity. We're happy to be helpful to folks to help them set up programs.  But the number one thing is to really be very aware of the power of saying something about doing exercise, just simply the power of saying, "I want you to be moving." Because frankly, I don't think anybody listening to this would disagree, no one benefits from sitting on the couch all day, no one. No one, no one. It doesn't matter how acute their medical issues are. We get people out of bed. We try to move people even when they're in the hospital. So I think saying something is huge. And then, if you can, applying a triage tool, if you can get something embedded within your clinical flow so that you can understand who it is that needs to go to physical therapy as opposed to who's ready for an exercise program. Those are the two things. So triage and referral is kind of step one. And if you can get that done, the rest will fall into place. Dr. Pedro Barata: This is really powerful message, where one, awareness of the care teams. Number two, bring it up to the patient. And then working on the referral, triage and referral process. That's fantastic. Another aspect that comes up quite a bit is like, "Look, this is great, but we have a system that relies on payers to make things happen, or at least to get them approved." And that can be very different or heterogeneous. The coverage can be different. Sometimes already going through a system programs for interventions, therapeutic interventions, let alone probably the insurance is not going to cover that. Is that true? Is it not true? How do you walk through the different insurance supports, perhaps, depending on where you're practicing? Dr. Kathryn Schmitz: You've just hit on the hot button. I've been working on this issue for about nine years now, trying to figure out using efforts to talk to CMS and see if we can get third party payer coverage going. We were making good progress there, and there was a change of administration and a new focus on "Make America Healthy Again," the MAHA movement. And, you know, CMS is really no longer interested in one-off national coverage determination. They instead, they want to know, "How do we make exercise happen for every American over 65?" And my question is, "Well, wait a minute, cancer patients are not just older patients. There's a lot going on there. They need something special." So I've been working on that. It's been working with accrediting bodies for policy with a little p. Very proud of the work that I've done in collaboration with the National Accreditation Program for Breast Centers, trying to get standards to get exercise referrals for breast patients. And I'm currently holding my breath to see whether the CoC is going to try to make some forward motion in this area as well, crossing all period appendages, waiting for news there. So it's not paid for unless it's done by a physical therapist. And, you know, there's published evidence and I have plenty of evidence from UPMC as well, that people don't really want to go to the physical therapist for this. I'm not saying physical therapists aren't great. Physical therapists are great, and there are people who really need to go to physical therapy, and we try hard to get those patients connected. But for the patients that are ready for something more than physical therapy, we really have an uphill battle to try to figure out what insurers are willing to pay for and what the return on investment is.  One of the challenges with the return on investment is that the timeline, time course for return on investment for American insurers is about one year. And I'll remind you that the time course for return on investment for CHALLENGE was 7.9 years. So we have a mismatch there. So we're trying to figure out if we can produce the evidence to show that there is an improvement in unplanned health care utilization. We have documented that for breast cancer. We're working on it for other cancers. If we can document that it is worthwhile to the insurer to pay for these programs, then I believe that they will pay for them. You know, my conversations are very positive with UPMC, which is a very large insurer and a large health plan. We're slowly working our way towards the middle, where there's a program that they can pay for and a program that is efficacious. That's the puzzle we're trying to solve for right now. Dr. Pedro Barata: This has been wonderful and super helpful. Before we wrap it up, is there anything else you would like to share with our listeners? Dr. Kathryn Schmitz: I want to make sure that your audience is aware that there are a variety of ways that exercise oncology is practiced. The program that most oncologists will be familiar with is LIVESTRONG, which is a program at the YMCA. It's a free program. At one point, there were over 800 locations across the U.S. They have contracted since COVID, probably because of COVID. So they still do exist but imagine, if you will, telling your patients that chemo is only available Tuesdays and Thursdays at 7:00 p.m. It would be difficult for patients to get there and get the chemotherapy. The same thing is true for the LIVESTRONG program. It's a fantastic, fantastic program for people who are able to get there, but that's one option. Another option for patients is there are a variety of online opportunities. I'll call out 2Unstoppable for women's cancers. It's literally the number 2Unstoppable.org. It's a free program available to women with cancer to have live, small group training programs. And they're based in Virginia, but they have programs all over the country. And then finally, I just want to overemphasize the app, the Cancer Exercise app. It's literally called Cancer Exercise in the app store. And that is a super duper easy button, very comprehensive, developed by a nurse scientist, Anna Schwartz. And then there are a variety of books. I wrote a book called Moving Through Cancer. There's a new book out [MyExerciseMedicine for Cancer] by Dr. Rob Newton as well, who's an Australian author. And there are certifications for exercise professionals that folks can look into as well through the American College of Sports Medicine. Dr. Pedro Barata: Dr. Schmitz, this is fantastic. Thank you for sharing those great insights with us. Super, super helpful. Thank you for taking the time. Dr. Kathryn Schmitz: Thank you so much. Dr. Pedro Barata: Thank you to our listeners for your time today. Remember, you'll find links to Dr. Schmitz's fantastic Educational Book as well as the JCO articles in the transcript of this episode. I'll invite all of you to go and read. And we'll also include a link to Dr. Schmitz's book titled Moving Through Cancer: An Exercise and Strength Program for the Fight of Your Life, which empowers patients and caregivers in simple five steps.  So with that, please join us again next month on By the Book for more insights on key advances and innovations that are shaping modern oncology. Thank you very much for your attention. 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. Pedro Barata    @PBarataMD     Dr. Kathryn Schmitz @fitaftercancer Follow ASCO on social media:           @ASCO on X (formerly Twitter)           ASCO on Bluesky          ASCO on Facebook           ASCO on LinkedIn           Disclosures:        Dr. Pedro Barata:    Stock and Other Ownership Interests: Luminate Medical    Honoraria: UroToday    Consulting or Advisory Role: Bayer, BMS, Pfizer, EMD Serono, Eisai, Caris Life Sciences, AstraZeneca, Exelixis, AVEO, Merck, Ipson, Astellas Medivation, Novartis, Dendreon    Speakers' Bureau: AstraZeneca, Merck, Caris Life Sciences, Bayer, Pfizer/Astellas    Research Funding (Inst.): Exelixis, Blue Earth, AVEO, Pfizer, Merck     Dr. Kathryn Schmitz: Patents, Royalties, Other Intellectual Property: Fees from the educational program developed by Dr. Schmitz that is now offered through Klose Training and Consulting.

Dr. Aly-Khan Lalani and Dr. Christopher Wallis also highlight Canadian-led innovation in the GUNS trial and early data from the PAnTHA study, and discuss how Prostate Cancer Working Group 4 may redefine trial design. Episode 35 is the first of three ASCO GU recap episodes, so don't miss Episode 36 on bladder cancer and Episode 37 on kidney cancer!The View on GU with Lalani & Wallis integrates key clinical data from major conferences and high impact publications, sharing meaningful take home messages for practising clinicians in the field of genitourinary (GU) cancers. Learn more about The View on GU: theviewongu.caThis podcast has been made possible through unrestricted financial support by Pfizer, Tolmar, AbbVie, Astellas, Eisai, Ipsen, Merck, Bayer, TerSera.

Dr. Aly-Khan Lalani and Dr. Christopher Wallis discuss practice-changing data in non-muscle invasive and muscle-invasive bladder cancer, including perioperative strategies,bladder-sparing approaches, and emerging targeted therapies. Don't forget to watch or listen to Episode 35 and Episode 37 for updates on prostate and kidney cancer!The View on GU with Lalani & Wallis integrates key clinicaldata from major conferences and high impact publications, sharing meaningful take home messages for practising clinicians in the field of genitourinary (GU) cancers. Learn more about The View on GU: theviewongu.caThis podcast has been made possible through unrestricted financial support by Pfizer, Tolmar, AbbVie, Astellas, Eisai, Ipsen, Merck, Bayer, TerSera.

Dr. Aly-Khan Lalani and Dr. Christopher Wallis also discuss the RAMPART trial, LITESPARK-011, and the K-COMPASS model. This final recap episode highlights how evolving adjuvant strategies and combination sequencing are reshaping the kidney cancer landscape. Be sure to listen to Episodes 35 and 36 for the full ASCO GU recap, covering key updates in prostate and bladder cancer!The View on GU with Lalani & Wallis integrates key clinical data from major conferences and high impact publications, sharing meaningful take home messages for practising clinicians in the field of genitourinary (GU) cancers. Learn more about The View on GU: theviewongu.caThis podcast has been made possible through unrestricted financial support by Pfizer, Tolmar, AbbVie, Astellas, Eisai, Ipsen, Merck, Bayer, TerSera.

This interview is brought to you in partnership with Eisai and is part of the Journey to Diagnosis series.Eisai: https://www.eisai.com/index.htmlJourney to Diagnosis: https://beingpatient.com/journey-to-diagnosis/Ben Draper was just 47 when he was diagnosed with early-onset Alzheimer's. In the years leading up to that diagnosis, he and his wife, Robin, began noticing changes. Ben struggled with everyday tasks that used to come easily, such as sending text messages, using a phone or computer, managing time, and doing simple math. While running his construction business, he realized he could no longer read a tape measure. Even following GPS while driving became difficult.Early testing revealed significant cognitive impairment, followed by an extensive medical workup that included an MRI and a spinal tap. The results showed amyloid plaque, and, with a strong family history of Alzheimer's, Ben later learned he also carries a genetic link to the disease.Today, Ben and Robin are focused on living each day to the fullest. They document their experiences on TikTok (@draperfamilylife) to help others feel less alone and to raise awareness about early-onset Alzheimer's.In this conversation with Being Patient's founder Deborah Kan, Ben and Robin describe the emotional whiplash of fearing a rapidly fatal diagnosis like Creutzfeldt-Jakob disease before receiving clarity, and the unexpected relief that can come with finally having the early-onset Alzheimer's diagnosis. They talk candidly about Ben's symptoms and how financial and care gaps can leave younger families scrambling for disability coverage, insurance, and support. Above all, they return to a guiding mindset, focus on what Ben can still do, lean on community, and make each day count.----Visit Being Patient for more Alzheimer's and brain health coverage: https://www.beingpatient.com/Follow Being PatientTwitter: https://twitter.com/Being_PatientInstagram: https://www.instagram.com/beingpatientvoices/Facebook: https://www.facebook.com/beingpatientalzheimersLinkedIn: https://www.linkedin.com/company/being-patientBeing Patient is an editorially independent journalism outlet covering brain health, cognitive science, and neurodegenerative diseases. Our Live Talk series features interviews with experts and people living with dementia.Watch more Live Talks: https://beingpatient.com/live-talks/

This interview is brought to you in partnership with Eisai and is part of the Journey to Diagnosis series.Eisai: https://www.eisai.com/index.htmlJourney to Diagnosis: https://beingpatient.com/journey-to-diagnosis/ What are the early signs of primary progressive aphasia (PPA)?In this Being Patient Live Talk, Samuel Valverde and his wife, Heather, share their journey to a diagnosis of primary progressive aphasia, a form of cognitive impairment that affects language and communication.Samuel Valverde is a Desert Storm combat veteran and former police chief in Waelder, Texas, who built his life around discipline, service, and staying sharp under pressure. But over time, subtle changes began to appear — missed court dates, forgotten details, and increasing difficulty with focus, planning, and speech.In 2022, while being treated for PTSD, Samuel's psychologist noticed changes that seemed to go beyond trauma. After months of testing — including cognitive evaluations, speech therapy, MRIs, and a PET scan — Samuel was diagnosed at age 53 with primary progressive aphasia (PPA).In this conversation with Being Patient's Mark Niu, Samuel and Heather talk openly about:Recognizing the early warning signs of PPAThe road to diagnosisHow PPA affects speech and daily lifeThe emotional impact on the whole familyAdjusting roles as a couple after diagnosisFinding resilience, support, and hopeIf you or someone you love is living with PPA, young-onset Alzheimer's, or another form of dementia, this conversation offers insight, support, and practical perspective.Visit Being Patient for more Alzheimer's and brain health coverage: https://www.beingpatient.com/Follow Being PatientTwitter:   / being_patient  Instagram:   / beingpatientvoices  Facebook:   / beingpatientalzheimers  LinkedIn:   / being-patient  Being Patient is an editorially independent journalism outlet covering brain health, cognitive science, and neurodegenerative diseases. Our Live Talk series features interviews with experts and people living with dementia.

Dr. Monty Pal and Dr. Ari Rosenberg discuss the evolution of treatment strategies in head and neck cancers, including the challenges of treating both HPV-positive and HPV-negative disease and the emergence of blood-based biomarkers to advance personalized therapy across different subtypes. TRANSCRIPT Dr. Monty Pal: Hello and welcome to the ASCO Daily News Podcast. I'm your host, Dr. Monty Pal. I'm a medical oncologist, professor, and vice chair of academic affairs at the City of Hope Comprehensive Cancer Center in Los Angeles. Today, we're going to explore the evolving landscape of treatment strategies in head and neck cancer management, including locoregionally advanced head and neck squamous cell carcinoma, which happens to be on the rise in United States, in part due to spike in HPV-mediated oropharyngeal cancers. We're also going to discuss the emerging strategies of using blood-based biomarkers to really advance personalized therapy. Joining me for this discussion is Dr. Ari Rosenberg. He's a medical oncologist focused on head and neck cancer, and he's an associate professor – congratulations on the recent promotion – at the University of Chicago. The University of Chicago has really produced luminaries in this field, Dr. Rosenberg included. I've had the pleasure of getting to know Dr. Ezra Cohen over the years, who really had his grounding there, and of course Everett Vokes, former ASCO President. I'm really looking forward to this conversation, Ari. Thanks so much for joining us. Dr. Ari Rosenberg: Thanks, Monty. Thanks for the invitation. Dr. Monty Pal: You got it. And just a quick note for our listeners, our full disclosures are going to be in the transcript at the end of this episode. So let's start with the basics, if you don't mind. So, head and neck cancers are very diverse and they're challenging, right? In the sense that they're near vital organs, the treatments, you know, as we all saw during fellowship, if not now in clinical practice. They can really have such a major impact on vital organ function, speech, swallowing, et cetera. Can you just comment on head and neck cancers that are on the rise in the U.S.? I alluded to this briefly. Particularly, we've heard this in the context of colorectal cancer and so forth. Are you actually seeing younger adults being affected by this? Dr. Ari Rosenberg: Yeah, thanks for that. The vast majority of head and neck cancers are head and neck squamous cell carcinomas, as I'm sure many of the listeners recall as well from fellowship or their current training. And as you alluded to, the organ function, long-term and functional quality of life outcomes are quite important, particularly in the context that these develop in high value real estate, parts of our head and neck area that we use for speaking, swallowing, all sorts of other essential functions as well. As you also alluded to, we think of this in two different particular subtypes of head and neck cancer. The historical head and neck cancer from 50, 60 years ago was almost exclusively related to carcinogen exposure, tobacco, alcohol use, and that subtype of carcinogen-induced head and neck cancer has been slowly declining. However, over the last now several decades, we've been seeing an increase in primary oropharyngeal squamous cell carcinoma, mostly tonsil, base of tongue. These are attributable to HPV, human papillomavirus exposure. And that's now the majority of the head and neck cancers that we tend to see in our clinic. As you also alluded to, these have very different prognoses as well. HPV-related head and neck cancer has a much more favorable prognosis where much of the interest has been in can we de-intensify to optimize long-term function? But then the non-HPV-related head and neck cancer, or what we call HPV-negative head and neck cancer, continue to be very, very challenging. We only managed to cure about half of these folks, with many of these patients developing the current disease. These patients, in addition to being difficult to treat, also have major impacts both in terms of the treatments they undergo as well as their disease that can impact their function and quality of life. And you hinted at this a little bit, but we have been seeing an increase in younger patients with HPV-negative head and neck cancer as well, which is quite concerning. Younger patients, oftentimes never smokers, never drinkers, who are developing non-HPV-negative head and neck cancer. And that's been a little bit of a more recent trend that we've been seeing as well. So, definitely a lot of work to be done to optimize and improve outcomes across all of these different head and neck cancer subtypes. Dr. Monty Pal: I mean, I'm just curious, you know, in the context of colorectal cancer, one of the things that we talk about is the potential role of the microbiome driving some of these young-onset cancers with, you know, perhaps there being an impact on, for instance, inflammation and the gut and what have you. Tell me about head and neck cancer. Is this anything known as to why younger patients might be getting diagnosed with non-HPV type cancers? It's odd to me. Dr. Ari Rosenberg: Yeah, it's a great question. A lot of people are working on it. I think we folks have hypotheses, but it hasn't totally panned out exactly what's going on there. It does have a little bit more of a tendency towards women, whereas historically head and neck cancer is much more common in men than it is in women. But lots of people working on that, whether it's related to chronic inflammation, whether it's related to the microbiome. Whether it's related to dental exposure, dental work. So, a lot of folks trying to parse that out because I agree with you, it needs to be identified alongside improving treatment paradigms for these patients, the young ones and the older patients as well. Dr. Monty Pal: Interesting, interesting. You know, one of the phenomena that was sort of coming around when I was in training 25 years ago was this role of sort of induction therapy for head and neck cancers. And of course, it's really come full circle now to include checkpoint inhibitors and so forth. Tell me a little bit about this and how you apply it, maybe in an HPV-mediated context, maybe in a non-HPV context. Dr. Ari Rosenberg: Yeah, absolutely. Induction chemotherapy, as you alluded to, or neoadjuvant chemotherapy, depending on what the locoregional treatment approach is. Similar to other cancer types where systemic control early on has many potential advantages in this setting. Now, in head and neck cancer, even though induction chemotherapy is quite active in head and neck cancer, both HPV-positive and HPV-negative with pretty good response rates. A survival advantage for all comers with local regionally advanced disease remains unproven. There's been two randomized trials, both underpowered, but essentially did not show a survival advantage, showing that induction chemotherapy for all patients with locoregionally advanced and neck cancer can't be justified for a survival advantage. That being said though, there remains a number of potential advantages of giving induction or neoadjuvant chemotherapy, of course, improving systemic control and debulking the disease early on has potential advantages, and predicting the responsiveness to subsequent radiation treatment. We know for some time in head and neck cancer that the percentage of shrinkage or the response to induction chemotherapy actually predicts outcome related to radiation as a dynamic biomarker where response can be used to select patients, for example, for de-escalated radiation has been an area of active investigation, active research. And it also remains a key opportunity to evaluate predictive biomarkers and understanding pre and post treatment to better understand the biology. I'll just add to your question that recently over this past year, we also saw phase 3 data for neoadjuvant immunotherapy for a subset of head and neck cancer that is surgically resectable. And so that's reintroducing the potential benefit in the immunotherapy era of incorporating immunotherapy in the neoadjuvant or the induction setting as part of the evolving treatment paradigm for these diseases. Dr. Monty Pal: That's really interesting. And you kind of alluded to already several topics that I plan to hit on, you know, for instance, the role of immune checkpoint inhibitors, induction, chemotherapy, and so forth. And you started to touch on biomarkers. And of course, I think that's something near and dear to many of us in academic oncology. One thing that we've started talking a lot about in the context of colorectal cancer is circulating tumor DNA. How do you think this might fit in the context of head and neck cancer? Can you give us a flavor for that? Dr. Ari Rosenberg: Yeah, absolutely. In head and neck cancer, the current landscape is most developed for circulating tumor DNA for HPV-related head and neck cancer. The advantage of HPV-related head neck cancer is that you have a distinctive HPV DNA that does tend to spill out into the peripheral blood and can be detected using various different blood-based assays. And because of that advantage as a tissue agnostic approach, it turns out that a number of HPV DNA plasma assays are actually quite sensitive and quite specific. And a number of them have indeed been commercialized. Of course, not only for detecting a baseline, but also grading responsiveness during treatment and probably most importantly in the post-treatment surveillance setting, the detection of HPV DNA in the plasma remains a very important and substantial predictor of developing recurrent disease. There's been a number of trials that have been emerging looking at ctDNA and HPV-related head and neck cancer, using it, for example, as a strategy to deescalate patients. That was something we saw this past ASCO from the Dana-Farber group, and also using it to early detect recurrence and potentially intervene earlier for patients with minimal residual disease positivity. So, that remains evolving and as many folks are, I think, already using it in the clinic. But ctDNA also has a lot of potential for HPV-negative head and neck cancer. This is actually a bit more challenging to develop because you don't have that HPV DNA that you can track predictably because the tumor is an HPV- negative disease are much more heterogeneous, but there are a number of data that are coming out both for personalized assays such as Signatera or some of the other assays that require tumor. Unlike colon cancer, which you referenced, where most patients get surgery upfront, in head and neck cancer, many of the patients receive non-surgical pre-chemoradiation. So sometimes the amount of tumor available to generate a personalized assay is more limited and can be one of the challenges that we see in head neck cancer. But certainly that also seems to be emerging. And there's also further assays that are being developed for HPV-negative head neck cancers, such as methylomic signatures and others that may be tissue informed or tissue agnostic. And these are also emerging, particularly in the post-treatment surveillance setting as strong predictors of recurrent disease. So while we're certainly behind some of these other more common tumor types, colon cancer, lung cancer, we're right there with them and more and more trials are going report out, including a number of trials in our upcoming [University of Chicago] Head and Neck Cancer Symposium where I'll be presenting some data and others in the field will be presenting some data looking at ctDNA both for HPV-positive and for HPV- negative to try to improve outcomes for these patients. Dr. Monty Pal: That's so interesting. I've got to tell you that in kidney cancer, what I deal with day to day is a very low shedding disease, right? So techniques as opposed to ctDNA looking for tumor-informed information, that might be less preferred to something like methylomics where you might not necessarily be so contingent on what's happening in the primary tumor. I'm really interested in you mentioning that. Just a point of clarification, this is something I'm trying to wrap my head around. You'd mentioned circulating tumor HPV DNA, right? I assume this is markedly different from just looking for HPV titers in the patient, right? So is this actually incorporated elements of HPV within, you know, essentially host genome, if you will? Dr. Ari Rosenberg: Yeah, correct. This is circulating tumor HPV DNA. And we think of it biologically as a plasma-based tumor DNA biomarker that's specific for HPV-related head and neck cancers. Dr. Monty Pal: Got it, got it. It makes me wonder whether or not this might be applicable to diseases like cervical cancer and so forth where there's also extensively, you know, biology driven by HPV. Is that fair? Dr. Ari Rosenberg: Yes, definitely. And in the head and neck cancer field, much of this ctDNA actually was derived from a different viral mediated head neck cancer, is less common in the U.S., but nasopharyngeal cancer, which is oftentimes associated with EBV. That has been a biomarker for quite some time in nasopharyngeal cancer. Of course, in places where EBV-associated nasopharyngeal cancer, is endemic, such as East Asia, this has been around for quite some time, but we've been using that in the U.S., and there's been trials that have used EBV DNA plasma to predict recurrence and stratify for adjuvant treatment, for example. And so now with HPV, it's much more applicable to our US population because the vast majority of our head and neck cancer patients that we see in the US that are viral mediated in the US tend to be HPV-related. So having assays that we can use to improve outcomes for that biological subset remains of particular interest for us. Dr. Monty Pal: Yeah, that's fascinating. By the way, for the fellows listening, there's tons of boards pearls here that Dr. Rosenberg shared, EBV-associated cancers, the role of HPV and treatment association. So if you're recertifying anytime soon, I definitely think there's notes to take from this conversation indeed. I wanted to shift gears a little bit. And obviously, you're a prolific researcher. I don't think anyone goes through their fellowship in medical oncology without recounting these experiences of our head and neck patients really suffering from treatment-related toxicities. It's a real challenge. And I'm just wondering, I know a big body of work that you're focused on is really using multimodality treatment paradigms to perhaps reduce the cumulative treatment burden of patients with head and neck cancers. Can you talk about that a little bit? Dr. Ari Rosenberg: Yeah, definitely. Thanks for the question. And before I start going into some of the strategies, I'll just say that head and neck cancer, this is particularly for the fellows that are listening as well, just in reference to your prior comment, that this is really a multidisciplinary disease. At our center, all head and neck cancer patients are seen upfront at that first visit by all three specialties, med onc, rad onc, and surgery, because the choice and sequencing of modalities to optimize not only survival, but also functional quality of life outcome is so critical. And I think that's probably the biggest takeaway for anyone who treats a lot of head and neck cancer or will be treating a lot of head and neck cancer in the clinic. But in terms of more specific attempts at trying to optimize some of those parameters that you described, we really think about these separately in terms of HPV-positive and HPV-negative head and neck cancer. For HPV-positive head and neck cancer, the cure rates are quite high with chemo radiation, although not for everyone. There's still about 15, 10 to 15 % of folks that will develop a recurrence. But for the vast majority of patients, standard chemoradiation is quite a cure to therapy, but the toxicity associated with that can be quite substantial. And so there's been a number of attempts to try to deescalate treatment. It turns out that deescalating everyone with locoregionally advanced HPV-positive head and neck cancer is not a good strategy because it's not able to select out the patients that really do need full dose treatment. And we have seen some negative trials that show inferior outcomes when everyone is deescalated. But what does remain promising is again, trying to select out who the best candidates are for deescalated treatment. The folks at MSK have hypoxia imaging that they're using in trials that looks quite promising to select for the more favorable deescalatable biology. At our center, we've been interested in using induction chemotherapy to stratify response and select patients for deescalated treatment with excellent survival outcomes and reduce toxicity with deescalated treatment. And more recently, ctDNA that us and other groups, such as the Dana-Farber group, is using. And that also looks quite promising. Again, how do you select the patient who will do well with less radiation versus the ones that really need the full doses and volumes of radiation? And then for HPV-negative head and neck cancer, this is a much trickier disease because already the survival outcomes are not like we want it to be. Trying to figure out how to improve survival outcomes remains an important thing. Using immunotherapy seems to be one of the key cornerstones to that. But these are patients that also suffer from a lot of toxicity related to their treatment. We completed a trial not too long ago that we published this past year where we, in HPV-negative head and neck cancer patients, de-intensified the radiation for responders to neoadjuvant chemoimmunotherapy. And those patients did similar, if not even a little bit better, than the non-responders who got full dose treatment. So something that does warrant further investigation as well. How do we not only improve survival for those patients, but also reduce some of the long-term toxicities? Dr. Monty Pal: This is brilliant. I'm taking so many notes as you were mentioning these items. There are so many areas where I think the research crosses over. I already mentioned, know, ctDNA, for instance, and metabolomics and the places where that might apply to kidney cancer. The hypoxia imaging really caught my ear too. Obviously, kidney cancer is disease highly predicated on hypoxia. So thank you for all of this. We've got about a minute or so. So, I'm going to ask you for a really tall task here. Can you tell us what you foresee being some of the biggest challenges that sort of lie ahead and head and neck cancer. You've already kind of alluded to it with ongoing research, but if you had to pick maybe 2, 3 problems, the very most that we really need to get to and head and neck cancer, what would that be? Dr. Ari Rosenberg: Yeah, that's a great question. Obviously, lots of things to be done, but if I'm going to limit it to just a couple, I would say number one is really trying to improve the survival for HPV negative local regionally advanced head and neck cancer. We talked early on about how we are seeing, you know, of course we see many of these people that were smokers and drinkers, but also seeing these in younger patients, in patients without a history of tobacco use. Some of these are very biologically aggressive and we need better treatments beyond surgery, beyond chemo radiation, beyond immunotherapy to improve outcomes for these patients and cure more of them. So, I would say that's one big area. And the other is, which we didn't speak about so much in this talk, but remains one of the biggest challenges that we see in the clinic is the recurrent metastatic head and neck cancer patients. This is an incredibly challenging disease to treat, not only with poor survival, but also with substantial impacts on quality of life and function. mean, these are bad recurrences that cause a lot of pain, functional deficits, really impacts quality of life as well. So developing novel therapies, many of which are currently in clinical trials and many of which are currently continuing to be developed, remains so critical. How do we develop better systemic therapies, better targeted therapies, better biomarkers for recurrent metastatic head neck cancer to improve their survival and quality of life and functional outcomes. Those are the two big areas that require the most work at this time within the head and neck cancer field. Dr. Monty Pal: That's brilliant. I mean, I have to tell you I could probably talk to you all day about this, such a fascinating topic. It's a very exciting time in the field. Thank you, Dr. Rosenberg, for all your incredible contributions and thanks for sharing with us your insights on the ASCO Daily News Podcast. Dr. Ari Rosenberg: Yeah, and thanks for the introduction. Hope to do it again soon. Dr. Monty Pal: And many thanks to our listeners for your time today. If you value the insights that you hear from the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. More on today's speakers:      Dr. Monty Pal   @montypal  Dr. Ari Rosenberg @AriRosenbergMD Follow ASCO on social media:           ASCO on X     ASCO on Bluesky          ASCO on Facebook           ASCO on LinkedIn           Disclosures:        Dr. Monty Pal:       Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview      Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical      Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis  Dr. Ari Rosenberg:     Stock and Other Ownership Interests: Privo Technologies Consulting or Advisory Role: Nanobiotix, EMD Serono, Vaccitech, Novartis, Eisai, Astellas Pharma, Regeneron, RAPT Therapeutics, Geovax Labs, Janssen, Summit Therapeutics Speakers' Bureau: Coherus Biosciences Research Funding (Inst.): Hookipa Biotech, EMD Serono, Purple Biotech, Bristol-Myers Squibb/Celgene, BeiGene, Abbvie, Astellas Pharma, Pfizer, Janux Therapeutics

Dr. Pedro Barata and Dr. Ugwuji Maduekwe discuss the evolving treatment landscape in gastroesophageal junction and gastric cancers, including the emergence of organ preservation as a selective therapeutic goal, as well as strategies to mitigate disparities in care. Dr. Maduekwe is the senior author of the article, "Organ Preservation for Gastroesophageal Junction and Gastric Cancers: Ready for Primetime?" in the 2026 ASCO Educational Book. TRANSCRIPT Dr. Pedro Barata: Hello, and welcome to By the Book, a podcast series from ASCO that features compelling perspectives from authors and editors of the ASCO Educational Book. I'm Dr. Pedro Barata. I'm a medical oncologist at University Hospitals Seidman Cancer Center and an associate professor of medicine at Case Western Reserve University in Cleveland, Ohio. I'm also the deputy editor of the ASCO Educational Book. Gastric and gastroesophageal cancers are the fifth most common cancer worldwide and the fourth leading cause of cancer-related mortality. Over the last decade, the treatment landscape has evolved tremendously, and today, organ preservation is emerging as an attainable but still selective therapeutic goal. Today, I'm delighted to be speaking with Dr. Ugwuji Maduekwe, an associate professor of surgery and the director of regional therapies in the Division of Surgical Oncology at the Medical College of Wisconsin. Dr. Maduekwe is also the last author of a fantastic paper in the 2026 ASCO Educational Book titled "Organ Preservation for Gastroesophageal Junction and Gastric Cancers: Ready for Prime Time?" We explore these questions in our conversations today.  Our full disclosures are available in the transcript of this episode as well. Welcome. Thank you for joining us today. Dr. Ugwuji Maduekwe: Thank you, Dr. Barata. I'm really, really glad to be here. Dr. Pedro Barata: There's been a lot of progress in the treatment of gastric and gastroesophageal cancers. But before we actually dive into some of the key take-home points from your paper, can you just walk us through how systemic therapy has emerged and actually allowed you to start thinking about a curative framework and really informing surgery decision-making? Dr. Ugwuji Maduekwe: Great, thank you. I'm really excited to be here and I love this topic because, I'm terrified to think of how long ago it was, but I remember in medical school, one of my formative experiences and why I got so interested in oncology was when the very first trials about imatinib were coming through, right? Looking at the effect, I remember so vividly having a lecture as a first-year or second-year medical student, and the professor saying, "This data about this particular kind of cancer is no longer accurate. They don't need bone marrow transplants anymore, they can just take a pill." And that just sounded insane. And we don't have that yet for GI malignancies. But part of what is the promise of precision oncology has always been to me that framework. That framework we have for people with CML who don't have a bone marrow transplant, they take a pill. For people with GIST. And so when we talk about gastric cancers and gastroesophageal cancers, I think the short answer is that systemic therapy has forced surgeons to rethink what "necessary" really means, right? We have the old age saying, "a chance to cut is a chance to cure." And when I started out, the conversation was simple. We diagnose the cancer, we take it out. Surgery's the default. But what's changed really over the last decade and really over the last five years is that systemic therapy has gotten good enough to do what is probably real curative work before we ever enter the operating room. So now when you see a patient whose tumor has essentially melted away on restaging, the question has to shift, right? It's no longer just, "Can I take this out?" It's "Has the biology already done the heavy lifting? Have we already given them systemic therapy, and can we prove it safely so that maybe we don't have to do what is a relatively morbid procedure?" And that shift is what has opened the door to organ preservation. Surgery doesn't disappear, but it becomes more discretionary. Necessary for the patients who need it, and within systems that can allow us to make sure that we're giving it to the right patients. Dr. Pedro Barata: Right, no, that makes total sense. And going back to the outcomes that you get with these systemic therapies, I mean, big efforts to find effective regimens or cocktails of therapies that allow us to go to what we call "complete response," right? Pathologic complete response, or clinical complete response, or even molecular complete response. We're having these conversations across different tumors, hematologic malignancies as well as solid tumors, right? I certainly have those conversations in the GU arena as well. So, when we think of pathologic CRs for GI malignancies, right? If I were to summarize the data, and please correct me if I'm wrong, because I'm not an expert in this area, the traditional perioperative chemo gives you pCRs, pathologic complete response, in the single digits. But then when you start getting smarter at identifying biologically distinct tumors such as microsatellite instability, for instance, now you start talking about pCRs over 50%. In other words, half of the patients' cancer goes away, it melts down by offering, in this case, immunotherapy as a backbone of that neoadjuvant. But first of all, this shift, right, from going from these traditional, "not smart" chemotherapy approaches to kind of biologically-driven approaches, and how important is pCR in the context of "Do I really need surgery afterwards?" Dr. Ugwuji Maduekwe: That's really the crux of the entire conversation, right? We can't proceed and we wouldn't be able to have the conversation about whether organ preservation is even plausible if we hadn't been seeing these rates of pathologic complete response. If there's no viable tumor left at resection, did surgery add something? Are we sure? The challenge before this was how frequently that happened. And then the next one is, as you've already raised, "Can we figure that out without operating?" In the traditional perioperative chemo era, pathologic complete response was relatively rare, like maybe one in twenty patients. When we go to more modern regimens like FLOT, it got closer to one in six. When you add immunotherapy in recent trials like MATTERHORN, it's nearly triple that rate. And it's worth noting here, I'm a health services-health disparities researcher, so we'll just pause here and note that those all sound great, but these landmark trials have significant representation gaps that limit and should inform how confidently we generalize these findings. But back to what you just said, right, the real inflection point is MSI-high disease where, with neoadjuvant dual-checkpoint blockade, trials like NEONIPIGAS and INFINITY show pCR rates that are approaching 50% to 60%. That's not incremental progress, that's a whole new different biological reality. What does that mean? If we're saying that 50% to 60% of the people we take to the OR at the time of surgery will end up having no viable tumor, man, did we need to do a really big surgery? But the problem right now is the gold standard, I think we would mostly agree, the gold standard is pathologic complete response, and we only know that after surgery. I currently tell my patients, right, because I don't want them to be like, "Wait, we did this whole thing." I'm like, "We're going to do this surgery, and my hope is that we're going to do the surgery and there will be no cancer left in your stomach after we take out your stomach." And they're like, "But we took out my stomach and you're saying it's a good thing that there's no cancer." And yes, right now that is true because it's a measure of the efficacy of their systemic therapy. It's a measure of the biology of the disease. But should we be acting on this non-operatively? To do that, we have to find a surrogate. And the surrogate that we have to figure out is complete clinical response. And that's where we have issues with the stomach. In esophageal cancer, the preSANO protocol, which we'll talk about a little bit, validated a structured clinical response evaluation. People got really high-quality endoscopies with bite-on biopsies. They got endoscopic ultrasounds. They got fine-needle aspirations and PET-CT, and adding all of those things together, the miss rate for substantial residual disease was about 10% to 15%. That's a number we can work with. In the stomach, it's a lot more difficult anatomically just given the shape of people's stomachs. There's fibrosis, there's ulceration. A fair number of stomach and GEJ cancers have diffuse histology which makes it difficult to localize and they also have submucosal spread. Those all conceal residual disease. I had a recent case where I scoped the patient during the case, and this person had had a 4 cm ulcer prior to surgery, and I scoped and there was nothing visible. And I was elated. And on the final pathology they had a 7 cm tumor still in place. It was just all submucosal. That's the problem. I'm not a gastroenterologist, but I would have said this was a great clinical response, but because it's gastric, there was a fair amount of submucosal disease that was still there. And our imaging loses accuracy after treatment. So the gap between what looks clean clinically and what's actually there pathologically remains very wide. So I think that's why we're trying to figure it out and make it cleaner. And outside of biomarker-selected settings like MSI-high disease, in general, I'm going to skip to the end and our upshot for the paper, which is that organ preservation, I would say for gastric cancer particularly, should remain investigational. I think we're at the point where the biology is increasingly favorable, but our means of measurement is not there yet. Dr. Pedro Barata: Gotcha. So, this is a perfect segue because you did mention the SANO, just to spell it out, "Surgery As Needed for Oesophageal" trial, so SANO, perfect, I love the abbreviation. It's really catchy. It's fantastic, it's actually a well-put-together perspective effort or program applying to patients. And can you tell us how was that put together and how does that work out for patients? Dr. Ugwuji Maduekwe: Yeah, I think for those of us in the GI space, we have SANO and then we also have the OPRA for rectum. SANO for the upper GI is what takes organ preservation from theory to something that's clinically credible. The trial asked a very simple question. If a patient with a GEJ adenocarcinoma or esophageal adenocarcinoma achieved what was felt to be a clinical complete response after chemoradiation, would they actually benefit from immediate surgery? And the question was, "Can you safely observe?" And the answer was 'yes'. You could safely observe, but only if you do it right. And what does that mean? At two years, survival with active surveillance was not inferior to those who received an immediate esophagectomy. And those patients had a better early quality of life. Makes sense, right? Your quality of life with an esophagectomy versus not is going to be different. That matters a lot when you consider what the long-term metabolic and functional consequences of an esophagectomy are. The weight loss, nutritional deficiencies that can persist for years. But SANO worked because it was very, very disciplined and not permissive. You mentioned rigor. They were very elegant in their approach and there was a fair amount of rigor. So there were two main principles. The first was that surveillance was front-loaded and intentional. So they had endoscopies with biopsies and imaging every three to four months in the first year and then they progressively spaced it out with explicit criteria for what constituted failure. And then salvage surgery was pre-planned. So, the return-to-surgery pathway was already rehearsed ahead of time. If disease reappeared, take the patient to the OR within weeks. Not sit, figure out what that means, think about it a little bit and debate next steps. They were very clear about what the plan was going to be. So they've given us this blueprint for, like, watching people safely. I think what's remarkable is that if you don't do that, if you don't have that infrastructure, then organ preservation isn't really careful. It's really hopeful. And that's what I really liked about the SANO trial, aside from, I agree, the name is pretty cool. Dr. Pedro Barata: Yeah, no, that's a fantastic point. And that description is spot on. I am thinking as we go through this, where can this be adopted, right? Because, not surprisingly, patients are telling you they're doing a lot better, right, when you don't get the esophagus out or the stomach out. I mean, that makes total sense. So the question is, you know, how do you see those issues related to the logistics, right? Getting the multi-disciplinary team, getting the different assessments of CR. I guess PETs, a lot of people are getting access to imaging these days. How close do you think this is, this kind of program, to be implemented? And maybe I would assume it might need to be validated in different settings, right, including the community. How close or how far do you think you see that being applied out there versus continuing to be a niche program, watch and wait program, in dedicated academic centers? Dr. Ugwuji Maduekwe: I love this question. So I said at the top of this, I'm a health equity/health disparities researcher, and this is where I worry the most. I love the science of this. I'm really excited about the science. I'm very optimistic. I don't think this is a question of "if," I think it's a question of "when." We are going to get to a point where these conversations will be very, very reasonable and will be options. One of the things I worry about is: who is it going to be an option for? Organ preservation is not just a treatment choice, and I think what you're pointing out very rightly is it's a systems-level intervention. Look at what we just said for SANO. Someone needs to be able to do advanced endoscopy, get the patients back. We have to have the time and space to come back every three to four months. We have to do molecular testing. There needs to be multi-disciplinary review. There needs to be intensive surveillance, and you need to have rapid access to salvage surgery. Where is that infrastructure? In this country, it's mostly in academic centers. I think about the panel we had at ASCO GI, which was fantastic. And as we were having the conversation, you know, we set it up as a debate. So folks were debating either pro-surveillance or pro-surgery. But both groups, both people, were presenting outcomes based on their centers. And it was folks who were fantastic. Dr. Molena, for example, from Memorial Sloan Kettering was talking about their outcomes in esophagectomies [during our session at GI26], but they do hundreds of these cases there per year. What's the reality in this country? 70% to 80% to 90%, depending on which data you look at, of the gastrectomies in the United States occur at low-volume hospitals. Most of the patients at those hospitals are disproportionately uninsured or on government insurance, have lower income and from racial and ethnic minority groups. So if we diffuse organ preservations without the system to support it, we're going to create a two-tiered system of care where whether you have the ability to preserve your organs, to preserve bodily integrity, depends on where you live and where you're treated. The other piece of this is the biomarker testing gap. One of the things that, as you pointed out at the beginning, that's really exciting is for MSI-high tumors. Those are the patients that are most likely to benefit from immunotherapy-based organ preservation. But here's the problem. If the patient isn't tested at time of initial diagnosis before they ever see me as a surgeon, the door to organ preservation is closed before it's ever open. And testing access remains very inconsistent across academic networks. And then there's the financial toxicity piece where, for gastrectomy, pancreatectomy, I do peritoneal malignancies, more than half of those patients experience significant financial toxicity related to their cancer treatment. We're now proposing adding at least two years, that's the preliminary information, right? It's probably going to be longer. At least a couple of years of surveillance visits, repeated endoscopies, immunotherapy costs. How are we going to support patients through that? We're going to have to think about setting up navigation support, geographic solutions, what financial counseling looks like. My patient for clinic yesterday was driving to see me, and they were talking about how they were sliding because it was snowing. And they were sliding for the entire three-hour drive down here. Are we going to tell people like that that they need to drive down to, right, I work at a high-volume center, they're going to need to come here every three months, come rain or snow, to get scoped as opposed to the one-time having a surgery and not needing to have the scopes as frequently? My concern, like I said, I'm an optimist, I think it is going to work. I think we're going to figure out how to make it work. I'm worried about whether when we deploy it, we widen the already existing disparities. Dr. Pedro Barata: Gotcha, and that's a fantastic summary. And as I'm thinking also of what we've been talking in other solid tumors, which one of the following do you think is going to evolve first? So we are starting to use more MRD-based assays, which are based on blood test, whether it's a tumor-informed ctDNA or non-informed. We are also trying to get around or trying to get more information response to systemic therapies out of RNA-seq through gene expression signatures, or development of novel therapeutics which also can help you there. Which one of these areas you think you're going to help this SANO-like approach move forward, or you actually think it's actually all of the above, which makes it even more complicated perhaps? Dr. Ugwuji Maduekwe: I think it's going to be all of the above for a couple of reasons. I would say if I had to pick just one right now, I think ctDNA is probably the most promising and potentially the missing piece that can help us close the gap between clinical and pathologic response. If you achieve clinical complete response and your ctDNA is negative, so you have clinical and molecular evidence of clearance, maybe that's a low-risk patient for surveillance. If you have clinical complete response but your ctDNA remains positive, I would say you have occult molecular disease and we probably need intensified therapy, closer monitoring, not observation. I think the INFINITY trial is already incorporating ctDNA into its algorithm, so we'll know. I don't think we're at the point where it alone can drive surgical decisions. I think it's going to be a good complement to clinical response evaluation, not a replacement. The issue of where I think it's probably going to be multi-dimensional is the evidence base: who are we testing? Like, what is the diversity, what is the ancestral diversity of these databases that we're using for all of these tests? How do we know that ctDNA levels and RNA-seq expression arrays are the same across different ancestral groups, across different disease types? So I think it's probably going to be an amalgam and we're going to have to figure out some sort of algorithm to help us define it based on the patient characteristics. Like, I think it's probably different, some of this stuff is going to be a little bit different depending on where in the stomach the cancer is. And it's going to be a little bit more difficult to figure out if you have a complete clinical response in the antrum and closer to the pylorus, for example. That might be a little bit more difficult. So maybe the threshold for defining what a clinical complete response needs to be is higher because the therapeutic approach there is not quite as onerous as for something at the GE-junction. Dr. Pedro Barata: Wonderful. And I'm sure AI, whether it's digitization of the pathology from the biopsies and putting all this together, probably might play a role as well in the future.  Dr. Maduekwe, it's been fantastic. Thank you so much for sharing your insights with us and also congrats again for the really well-done review published.  For our listeners, thank you for staying with us. Thank you for your time. We will post a link to this fantastic article we discussed today in the transcript of this episode. And of course, please join us again next month on the By the Book Podcast for more insights on key advances and innovations that are shaping modern oncology. Thank you, everyone. Dr. Ugwuji Maduekwe: Thank you. Thank you for having me. Watch the ASCO GI26 session: Organ Preservation for Gastroesophageal and Gastric Cancers: Ready for Primetime? 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. Pedro Barata   @PBarataMD    Dr. Ugwuji Maduekwe @umaduekwemd Follow ASCO on social media:          @ASCO on X (formerly Twitter)          ASCO on Bluesky         ASCO on Facebook          ASCO on LinkedIn          Disclosures:       Dr. Pedro Barata:   Stock and Other Ownership Interests: Luminate Medical   Honoraria: UroToday   Consulting or Advisory Role: Bayer, BMS, Pfizer, EMD Serono, Eisai, Caris Life Sciences, AstraZeneca, Exelixis, AVEO, Merck, Ipson, Astellas Medivation, Novartis, Dendreon   Speakers' Bureau: AstraZeneca, Merck, Caris Life Sciences, Bayer, Pfizer/Astellas   Research Funding (Inst.): Exelixis, Blue Earth, AVEO, Pfizer, Merck    Dr. Ugwuji Maduekwe: Leadership: Medica Health Research Funding: Cigna    

Synopsis: Fresh from the JPM 2026 in San Francisco, Alok Tayi welcomes Johan Luthman, Executive Vice President of R&D at Lundbeck, for a sweeping, deeply personal conversation on the future of neuroscience drug development. From his early days as a Swedish clinician-scientist to leading breakthrough Alzheimer's programs and rebuilding Lundbeck's pipeline from the ground up, Johan shares the pivotal moments—and phone calls—that shaped a 30-year career across AstraZeneca, Merck, Serono, and now Denmark's neuroscience powerhouse. The discussion dives into Lundbeck's bold strategic reset: letting biology lead, de-risking early in patients, embracing rare disease and sleep medicine, and making disciplined bets on monoclonal antibodies, migraine prevention, epilepsy, and neuroendocrine disorders. Johan explains how the company shifted capital toward innovation, rebuilt its portfolio through targeted acquisitions, and built one of the most advanced neuroscience pipelines in pharma today. In one of the episode's most powerful moments, Johan opens up about his personal motivation—caring for family members with Alzheimer's and dedicating his career to diseases of the brain. From AI-driven R&D productivity and adaptive trials to Denmark's unique foundation-owned pharma model, this conversation is a masterclass in scientific rigor, decision-making under uncertainty, and keeping patients at the center of everything. Biography: In 1991, Johan Luthman began his career in the pharmaceutical industry in Astra, later AstraZeneca. In 2005, Johan joined Serono as Head of Neuroscience & Immunology Research, and subsequently, in MerckSerono, as Therapy Area Head, Neurology & Immunology. In 2009, he became CEO of biotech start-up GeNeuro. In late 2009, Johan joined Merck as VP & Franchise Integrator for Neuroscience and Ophthalmology. In 2014, he came to Eisai where he was Senior Vice President and Head of Clinical Development. Johan joined Lundbeck as Executive Vice President, R&D in March 2019. Johan is a Swedish national and is trained as a Doctor of Dental Sciences from the Karolinska Institute, Sweden. He also holds a PhD in Neurobiology and Histology as well as an Associate Professor title from the Karolinska Institute, Sweden. Johan is a Member of the Board of Directors of Brain+.

This interview was brought to you in partnership with Eisai and is part of the Journey to Diagnosis series.Eisai: https://www.eisai.com/index.htmlJourney to Diagnosis: https://beingpatient.com/journey-to-diagnosis/Luke Davis spent four decades as a Dallas attorney — and an active husband, father, youth sports coach and school board member — before subtle memory changes raised concerns. In this Being Patient Perspectives interview, Luke and his wife, Paula Davis, share the early signs of Alzheimer's they noticed first, how they pursued answers, and what helped them move forward.After a primary care visit, Luke underwent cognitive testing, an MRI and an amyloid PET scan that confirmed plaque. In April 2023, just before his 69th birthday, he was diagnosed with early-stage Alzheimer's disease. Luke later learned he carries two copies of the APOE4 gene, a major genetic risk factor for Alzheimer's.Luke and Paula also discuss treatment and support — including Luke's experience with Leqembi (lecanemab) infusions — and how they've leaned on the Alzheimer's Association, community, and practical day-to-day strategies. Their message for newly diagnosed individuals and couples: Alzheimer's is a detour, not a dead end — and Luke is focused on “living with Alzheimer's, not dying from it.”Topics covered: early Alzheimer's symptoms, diagnosis journey, amyloid PET scan, APOE4, Leqembi/lecanemab, caregiving as a spouse, coping after diagnosis, living well with Alzheimer's, advocacy and support.#Alzheimers #EarlyAlzheimers #Leqembi #Lecanemab #APOE4 #Dementia #BrainHealth #BeingPatient---- If you loved watching this Live Talk, visit our website to find more of our Alzheimer's coverage and subscribe to our newsletter: https://www.beingpatient.com/Follow Being Patient: Twitter: https://twitter.com/Being_Patient_Instagram: https://www.instagram.com/beingpatientvoices/Facebook: https://www.facebook.com/beingpatientalzheimersLinkedIn: https://www.linkedin.com/company/being-patientBeing Patient is an editorially independent journalism outlet for news and reporting about brain health, cognitive science, and neurodegenerative diseases. In our Live Talk series on Facebook, former Wall Street Journal Editor and founder of Being Patient, Deborah Kan, interviews brain health experts and people living with dementia. Check out our latest Live Talks: https://beingpatient.com/live-talks/

Host: Charles Turck, PharmD, BCPS, BCCCP Guest: Kormal Jhaveri, MD, FACP Guest: Vanessa Soto-Romano, RN There's been recent progress with antibody-drug conjugates (ADCs) for HER2-negative breast cancers,1-3 and most recently, patients with metastatic HR+ HER2- breast cancer. The phase III TROPION-Breast01 study examined the efficacy and safety of datopotamab deruxtecan-dInk (Dato-DXd) compared to investigator's choice single-agent chemotherapy, resulting in the approval of this agent in January 2025. Joining Dr. Charles Turck to discuss Dato-DXd for patients with HR-positive, HER2-negative metastatic breast cancer, data from the TROPION-Breast01 trial, and strategies for managing select adverse reactions with this therapy are Dr. Komal Jhaveri and Nurse Vanessa Soto-Romano. Dr. Jhaveri is a breast medical oncologist and early drug development specialist at Memorial Sloan Kettering Cancer Center in New York, and Nurse Soto-Romano is a Clinical Trials Nurse, also at Memorial Sloan Kettering Cancer Center in New York. Dr. Komal JhaveriConsultant/advisory board role: Novartis, Pfizer, Genentech, Eisai, AstraZeneca, Blueprint Medicines, Daiichi Sankyo, Menarini/Stemline, Gilead, Scorpion Therapeutics, Bicycle Therapeutics, Olema Pharmaceuticals, Lilly/Loxo Oncology, Merck Pharmaceuticals, Zymeworks, Halda Therapeutics, Arivinas and RayzebioResearch Funding support to the Institution: Novartis, Genentech, AstraZeneca, Pfizer, Lilly/Loxo Oncology, Zymeworks, Gilead, PUMA Biotechnology, Merck Pharmaceuticals, Scorpion Therapeutics, Rayzebio, Eisai, Bicycle Therapeutics, Bridge Bio Oncology Therapeutics, and Blueprint Medicines. Nurse Soto-RomanoConsultant/advisory board role: AstraZeneca …

In Episode 33, Dr. Aly-Khan Lalani and Dr. Christoper Wallis sit down with Dr. Daniel Heng, Clinical Professor at the University of Calgary and Head of Medical Oncology at the Arthur J.E. Child Comprehensive Cancer Centre. Together, they explore the full landscape of mentorship and sponsorship in academic medicine, from what makes an exceptional mentee to how leaders identify and support rising talent.The View on GU with Lalani & Wallis integrates key clinical data from major conferences and high impact publications, sharing meaningful take home messages for practising clinicians in the field of genitourinary (GU) cancers. Learn more about The View on GU: theviewongu.caThis podcast has been made possible through unrestricted financial support by Novartis, Bayer, Astellas, Tolmar, Ipsen, J&J, Merck, Pfizer, Eisai and AbbVie.

Pfizer followed up its winning $10 billion bid forobesity startup Metsera by adding another molecule to its obesity cabinet, thisone from Chinese firm YaoPharma in a deal worth up to $1.9 billion licensing deal announced Tuesday. Meanwhile, Wave Life Sciences and Structure Therapeutics may have changed the weight loss landscape with early and mid-stagedata from their candidates that analysts called “very disruptive” and “highlycompetitive,” respectively.  At the FDA, the confusion and instability continuewith the retirement of agency veteran Richard Pazdur just three weeks into hisrole as CDER director. Pazdur's exit leaves the FDA with just three veteran leaders from one year ago. The CDC similarly made headlines last week as therevamped vaccines advisory committee voted to recommend postponing the hepatitis B vaccination from birth to two months of age for some infants. Meanwhile, the Clinical Trials on Alzheimer's Disease (CTAD)conference generated excitement in the space as Roche, Eisai and others presentednew data from their respective candidates. The star of the show was Roche'snext-gen antibody trontinemab, which lowered amyloid levels below the threshold of positivity in 92%of treated patients in a mid-stage study. Meanwhile, Eisai isdetermined to buck the losing the trend in the anti-tau space. The company's etalanetugreduced all measurable forms of MTBR-tau243—a specific biomarker of tau tanglepathology in Alzheimer's—in a Phase Ib/II trial, according to an oralpresentation at CTAD.  Finally, check outthis week's deep dives in BioPharm Executive on what pharmas are learning fromthe Chinese biotech sector and how Japan's pharma industry is setting itssights on the global market.

Dr. Pedro Barata and Dr. Ravin Garg discuss strategies to increase trial representation, including leveraging trial navigators and prioritizing pragmatic trial models, as featured in the ASCO Educational Book article, "Practical Guide to Clinical Trial Accessibility: Making Trial Participation a Standard of Care." TRANSCRIPT Dr. Pedro Barata: Hello, and welcome to By the Book, a podcast from ASCO featuring compelling perspectives from authors and editors of the ASCO Educational Book. I'm Dr. Pedro Barata. I am a medical oncologist at University Hospital Seidman Cancer Center and an associate professor of medicine at Case Western Reserve University in Cleveland, Ohio. I am also the associate editor of the ASCO Educational Book. We know that in recent years, the oncology community has increasingly prioritized the need to modernize clinical trial eligibility, reduce patient burden, and enhance diversity in trial participation. On that note, today we will be speaking about ways to enhance access to clinical trials with Dr. Ravin Garg. He is a hematologist oncologist at Maryland Oncology Hematology and also an assistant professor of oncology at Johns Hopkins Hospital in Baltimore. Dr. Garg is also the co-author of a fantastic paper in the ASCO Educational Book titled, "Practical Guide to Clinical Trial Accessibility: Making Trial Participation a Standard of Care."  Dr. Garg, welcome. Thanks for being here, and congrats on your paper. Dr. Ravin Garg: Thank you for having me, Pedro. I am excited to be here. Dr. Pedro Barata: [KI1]  Your paper is a wonderful, multidisciplinary piece that actually features perspectives from the different stakeholders, right? The patient advocacy, industry, community practice, and academia about these challenges in making trials more available. This podcast is a wonderful platform. It reaches out to a lot of folks within our community. So, I will start by asking you the obvious. Why do you think it is a must read for our community, for our listeners? Dr. Ravin Garg: So Pedro, thanks again for inviting me. You do a great job with these podcasts.  So, I think first and foremost, oncologists right now are under a lot of stress, just in terms of clinical volume. There is concern for research money, and how we get the best care for our patients. So I think this article is very important because it helps bring together, as you had mentioned, the stakeholders throughout academic to community practice and everywhere in between, and try to find how, as a team with different oncologists who partake in different aspects of oncology, can come together to streamline the process to try to get our patients on trials, or certainly have them have availability of trials, just if they are interested in going on them. Being in practice, we have had several challenges that we can talk about throughout this podcast, but I think it is a very important paper because it recognizes that at the end of the day, it takes a team effort for all of us in academics, community, industry, and pharmaceuticals to really come together as a team to really help put forth the trials for our patients. Dr. Pedro Barata: So, from the perspective of a community oncologist, how do you put together, or maybe you can describe some of the challenges that you see to increase trial participation in the community? Dr. Ravin Garg: Yes, Pedro, that is a great question, and it is something that I keep on thinking about and trying to find ways to be better at it myself. But I will say some of the challenges as a community doctor that I have seen for myself and talking to other colleagues. Number one, I do think there is a lot of stress on doctors in the community in general, Pedro. Oftentimes we are tasked to see a wide smorgasbord of patients, so we may not have the luxury of being a specialist in any particular tumor subtype. Like oftentimes, we will have to see lung cancer, the next one will be breast cancer, the next one could be CML, the next one could be thrombocytopenia. And as you know better than I do, Pedro, the field in each one of these disciplines is changing so rapidly: molecular genomics, radioligand treatments, different imaging tests, MRD testing for some of our hematologic malignancies. And I think one challenge we have in community is just keeping up with the basics of Oncology 101. In the process of doing that, it can be very difficult to sometimes remember that we have very exciting trials available for our patients. So, I think a lot of it is the day in and day out of being an oncologist is so taxing at times that oftentimes a research trial is not the first thing in our head space when we see a patient. I think number two, Pedro, at least in the community, and perhaps this is with academics too, is that we are bombarded, I would say, by a lot of messaging these days. We have in-baskets to go through, labs to go through, things of that nature. And in the process of a patient visit, seeing them, doing an exam, taking a history, trying to go over the NCCN guidelines on best practice for how to manage their care, at least for me at times, it is very hard to remember, "Hey, there might be a great trial available, whether within our network or maybe partnering with an academic center." So getting through a day can be fraught with a lot of peril and just difficulties, I would say. And I would say number three, Pedro, at least as, you know, I am in a private practice where I do see a wide range of benign and malignant hematology and solid tumors, so I would not call myself a specialist. And I think the challenge with that, at least for trials, Pedro, is that when you are a specialist or perhaps you are focusing on a couple of disease subtypes, you become more of an authoritative voice in those types of tumors, and you might be more aware of the trials within your network or perhaps in proxy with an academic center that you can offer your patient. So I think when sometimes we spread ourselves too thin, it can be very hard to be a thought leader, if you will, in a particular subtype of a malignancy, let's say, and maybe not be aware of a trial that could be really well-suited for your patient. In terms of ideas that myself and colleagues have had in terms of helping mitigate against some of these, I would say, setbacks or issues in the practice for trial enrollment, some of the things we have talked about, Pedro, is, number one, is we do partner with academic centers. So we live here in Maryland. We have several really fantastic academic centers. So, you know, oftentimes, not just within our practice of Maryland Oncology Hematology, we have a lot of great trials available here too, for certain, but in addition to that, we will often times work with doctors at Georgetown, Johns Hopkins, and Maryland if they have a compelling trial that we do not have within our network. It is really of the patient's interest, Pedro, to reach out to them in a collaborative manner to see if they have a trial that might be really compelling for your patient. So I do find myself collaborating a lot with colleagues in, like talented like yourself in academics. You know, I think you do a lot of GU malignancies. So as an example, like partnering with colleagues who are GU experts and say, "Hey, we have a patient with stage IV renal cell. These are the standard options I know, but are there any trials that you might have available?" I think the other thing that has been very helpful for us is having navigators within research, Pedro. Like as an example, what has really helped the uptake of trial enrollment for our center in Annapolis is having a research navigator because often times what they can do is, a priori, Pedro, before you see the patient and you are kind of formulating a standard of care treatment plan perhaps, they might tug you on the shirt and say, "Hey, we have a great trial here through Sarah Cannon, or there might be something else out there." And being aware of that when you go into a patient's room really provides a nice arena, if you will, to go and say, "The standard of care is here, but hey, we have a trial option that might be well suited for you, maybe perhaps even better, that we can talk about, too." So having research support in the community is really a huge boon, I think, Pedro, for us to really increase our enrollment for patients onto trials. Dr. Pedro Barata: Yes, I really love that, Ravin. So, let me switch gears a bit. I would love for you to talk a little bit about patient advocacy because they do play a huge role in cancer, and they address many barriers. How do you think we should leverage the patient advocacy groups to reduce patient burden and maybe have them really leverage patient advocacies to improve representation in clinical trials? What do we think we can do more? Dr. Ravin Garg: Oh, Pedro, I think they are very critically important. As a clinical oncologist now, and I would say this is for anyone in the field of medicine, you are exactly right. I think patients are bombarded by information. There are a lot of things online, whether it be TikTok, Facebook, Google, Yahoo, and people really just have a lot of information given to them. And some of it is fact driven, and some of it is not, Pedro. And oftentimes, I do think there can be at times a mistrust with some medical personnel. I think we are in an era where we are seeing that to some degree with some attributes of medicine. And I think of it as an opportunity for education for the patient and for myself as a physician. And I think patient advocates, to your point, which was well taken, serve as a bridge to both. And what I mean is that, you know, patient advocates are wonderful. They are, I think, outstanding communicators. They almost are a neutral party, Pedro, where many patients feel that they are an independent source of information that is free of bias, if you will. They are there to provide support, emotional support, scientific support for patients so they can make an informed decision. So, in terms of our practice right now, patient advocates is something that we are evolving in that capacity, I would say, Pedro. I think now more than ever, having more people as bridges of communication with care providers along with patients is of critical importance. And I would venture a guess, and I think this has been published, where patient advocates really can help tremendously in familiarizing patients with trials and what they are all about and maybe clear up some misconceptions of what trials, what the mission of trials are. Because I do think some patients, at least I have had a few over the years, where when they hear the term trial, they almost think they are being experimented upon, when, in point of fact, they could really help advance their care. That messaging along the way for some can may be mixed up a little bit. And so I think patient advocates is a really great way to offer more information for patients with a source they find very independent and trustworthy, if you will. And it can really help expedite, and I think make a more fruitful conversation for care providers, whether academic or community, and they might be more open-minded in terms of enrolling onto a trial. Dr. Pedro Barata: Wonderful. Yes, I agree. I agree with you completely.  So let's focus a little bit now on the folks designing the studies. We usually call them the sponsors. It might be an academic sponsorship, if you will, but we can also have pharma being the sponsor of a study. The angle from an academic design, it is not necessarily the same as what happens when we have pharma. And from that angle, how do you think a more inclusive research can be promoted? Dr. Ravin Garg: Oftentimes with trials, I think keeping them simple, as simple as we can. And what I mean by that is, often times for trials, Pedro, even for care providers who are enrolling, it can be daunting when there are a lot of different things involved, particularly, let's say, for investigator sponsored, which are incredibly brilliant science, incredible, but it can be a little bit daunting for patients and even the referring physician to talk about getting translational specimens, imaging, traveling to certain centers to get scans and biopsies and even different diagnostic testing like PSMA testing for, you know, prostate cancer. And it can, I think, be very intimidating for patients in terms of what might be required of him or her to enter onto a trial. Like, "This is not what I signed up for. This is laborious. This is a full time job for me. Do I have to pay for parking to go to a city? Do I have to pay for these imaging tests? And do I have to stay in a place for my family to enroll onto a trial?" So I think keeping trials as simple as possible, but yet cull the data we need as investigators where we can really advance the care, hopefully get approval for a drug, but also learn more about the medication and how it works for our patients. So I think simplifying language for trial is very important. I know when I have gone over studies for patients, Pedro, if it is a voluminous amount of information, they can right away get very intimidated. "Like, oh my goodness, this is like a term paper for college again," you know? I am joking, but you know, keeping language simplified is very important, I think, number one. And I feel that sometimes when they are asked to do a lot of different diagnostic testing, which is very important for translational work, I 100% understand, but I do think sometimes patients can get a little bit off put, if you will, and frustrated with the whole process of doing it. The second thing for our patients, Pedro, that they have mentioned to us when we put them on trials, not just within our own site but elsewhere, is that it takes a lot of time in terms of collecting information, perhaps a washout period from their last standard of treatment prior to enrollment onto a study. Many patients, Pedro, as you know better than I do, are in maybe crisis in terms of their health and their cancer might be growing, promulgating out of control, and they worry about not being able to expeditiously start onto a treatment, onto a trial. So that can lead to a lot of frustration. And one thing that you brought up, which was outstanding for me, is the enrollment criterion for some of our patients is felt to be somewhat strict. We have had some patients who may have had a remote history of a stage I malignancy that was by all accounts in remission, you know, let's say 4 or 5 years in the past, and the risk of recurrence at this point would be incredibly low, but they may not be able to enter onto a study because of some stringent criterion put forth. And that can be a little bit frustrating. In fact, I have had one or two patients who, as an example, with kidney issues, but the GFR was about 60, like right near a cutoff that oftentimes, as you know, we use where you can get into trial or not. And you know, if they are at 58, as an example, and otherwise they are a picture of health, a great candidate for a trial that will likely advance their care, and if the entry criterion is too stringent, that might be a lost opportunity for all parties involved, all stakeholders, if you will. I do appreciate the criterion for entry onto studies cannot be too liberalized. You have to have a certain baseline, but there is a little bit of a gray area and tension, of sorts, if you will, where the patient has a comorbid illness that is a disqualifying offense, but in practicality, perhaps it shouldn't be, especially if they are motivated and there is an opportunity to really advance their care. We have run into, not often, but sometimes in the past, I should say, where patients have been very off put because we try to get them onto a study and there may have been a particular feature or attribute in their underlying care that they couldn't get onto it. So I think having a little bit more thoughtfulness, perhaps, in terms of entry criterion and practicality, if you will, I think would really help enrollment onto studies. Dr. Pedro Barata: Really well said. Is there anything else that you would like to tell our listeners before we wrap up the podcast today? Dr. Ravin Garg: I would say just macroscopically speaking, it is really an honor to be an oncologist. I think I speak for both of us. Anyone listening who is thinking about the field, it is tremendous. Just the research, the bravery of our patients, and the thoughtfulness of our scientists like Pedro and translationalists and clinical trialists is really awe inspiring. So I have really loved this field. I will say from a trial perspective, we really need to enter as many patients as we can onto trials because the science is so brilliant now, the genomic underpinnings of the tumor, we are making great strides as a team of clinicians and scientists, translationalists. So the more that we can get people onto trials and get approved drugs, it is going to help them out in the end. So I think it is such an important time for all of us to come together as a community, find the best way to help our patients out. And clinical trials have to be at the forefront of how we can continue to advance care for our patients. Dr. Pedro Barata: Yeah, no Ravin, I really agree with you. We really need to increase access to clinical studies, and actually your paper is a great step in that direction by raising awareness, bringing up solutions, and again, collaboration, collaboration, collaboration is really a multidisciplinary effort to accomplish that.  Thank you so much for sharing your fantastic thoughts and insights with us. Dr. Ravin Garg: Thank you, Pedro. I am- you do a wonderful job with these podcasts. I am really honored to meet you and to be part of this. Dr. Pedro Barata: And thank you to our listeners for your time today. I encourage you to check out Dr. Garg's article in the 2025 ASCO Educational Book. We will post a link to the paper in our show notes. And please join us again next month on By the Book for more insights on key advances and innovations that are shaping modern oncology. Thank you for your attention. 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. Pedro Barata   @PBarataMD    Dr. Ravin Garg Follow ASCO on social media:          @ASCO on X      ASCO on Bluesky     ASCO on Facebook       ASCO on LinkedIn       Disclosures:       Dr. Pedro Barata:   Stock and Other Ownership Interests: Luminate Medical   Honoraria: UroToday   Consulting or Advisory Role: Bayer, BMS, Pfizer, EMD Serono, Eisai, Caris Life Sciences, AstraZeneca, Exelixis, AVEO, Merck, Ipson, Astellas Medivation, Novartis, Dendreon   Speakers' Bureau: AstraZeneca, Merck, Caris Life Sciences, Bayer, Pfizer/Astellas   Research Funding (Inst.): Exelixis, Blue Earth, AVEO, Pfizer, Merck    Dr. Ravin Garg: Patents, Royalties, Other Intellectual Property: Creator, editor, and writer of hemeoncquestions.com  

Navigating Dementia – Related Behaviors Evaluation and Credit:  https://www.surveymonkey.com/r/medchat85   Target Audience             This activity is targeted toward primary care physicians and advanced providers.   Statement of Need  This podcast will address common behavioral and psychological symptoms (BPSD) associated w/ dementia and provide strategies for clinicians to recognize and manage. Up to 90% of individuals with dementia can suffer from BPSD that can include agitation, anxiety, depression, hallucinations and aggression This can be challenging for care givers, patients and care teams.   Objectives List common behavioral and psychological symptoms (BPSD) associated with dementia. Identify environmental, medical and psychosocial factors that can contribute to BPSD. Discuss evidence-based strategies to evaluate and manage BPSD, minimizing antipsychotics and highlighting non-pharmacological.  Moderator Greg E. Cooper, M.D., Ph.D. Chief, Adult Neurology Medical Director, Memory Center Norton Neuroscience Institute.   Speaker Rachel Hart, D.O. Geriatric Medicine Physician Memory and Cognitive Disorders Specialist Norton Neuroscience Institute Memory Center   Planner Disclosure   The planners of this activity do not have any relevant financial relationships with ineligible companies to disclose.   Moderator and Speaker Disclosure The speaker, Gregory Cooper, M.D., Ph.D., discloses relevant financial relationships with Eli Lilly and Eisai (research). The moderator, Rachel Hart, D.O., discloses a relevant financial relationship with Eli Lilly (faculty).   All relevant financial relationships have been successfully mitigated.   Commercial Support   There was no commercial support for this activity.    Physician Credits Accreditation  Norton Healthcare is accredited by the Kentucky Medical Association to provide continuing medical education for physicians.   Designation  Norton Healthcare designates this enduring material for a maximum of .50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.   Nursing Credits Norton Healthcare Institute for Education and Development is approved as a provider of nursing continuing professional development by the South Carolina Nurses Association, an accredited approver by the American Nurses Credentialing Center's Commission on Accreditation. This continuing professional development activity has been approved for 0.50 ANCC CE contact hours. In order for nursing participants to obtain credits, they must claim attendance by attesting to the number of hours in attendance.     For more information related to nursing credits, contact Sally Sturgeon, DNP, RN, SANE-A, AFN-BC at (502) 446-5889 or sally.sturgeon@nortonhealthcare.org.   Social Worker Credits This activity will provide .50 hours of required continuing education units. National Association of Social Workers, Kentucky Chapter (NASW-KY) is an approved provider for social work credits through the Kentucky Board of Social Work. NASWKY#06/30/25.   For information about social worker credits, please send an email to cme@nortonhealthcare.org.   Resources for Additional Study/References Guideline Recommendations on Behavioral and Psychological Symptoms of Dementia: A Systematic Review https://pubmed.ncbi.nlm.nih.gov/38640961/   Nonpharmacological Interventions for Management of Behavioral and Psychological Symptoms of Dementia in Long-Term Care Facilities by Direct Caregivers: A Systematic Review https://pubmed.ncbi.nlm.nih.gov/35771069/   Date of Original Release | Dec. 2025; Information is current as of the time of recording.  Course Termination Date | Dec. 2027 Contact Information | Center for Continuing Medical Education; (502) 446-5955 or cme@nortonhealthcare.org   Also listen to Norton Healthcare's podcast Stronger After Stroke. This podcast, produced by the Norton Neuroscience Institute, discusses difficult topics, answers frequently asked questions and provides survivor stories that provide hope.   Norton Healthcare, a not for profit health care system, is a leader in serving adult and pediatric patients throughout Greater Louisville, Southern Indiana, the commonwealth of Kentucky and beyond. More information about Norton Healthcare is available at NortonHealthcare.com.

Dr. Linda Duska and Dr. Kathleen Moore discuss key studies in the evolving controversy over radical upfront surgery versus neoadjuvant chemotherapy in advanced ovarian cancer. TRANSCRIPT Dr. Linda Duska: Hello, and welcome to the ASCO Daily News Podcast. I am your guest host, Dr. Linda Duska. I am a professor of obstetrics and gynecology at the University of Virginia School of Medicine.  On today's episode, we will explore the management of advanced ovarian cancer, specifically with respect to a question that has really stirred some controversy over time, going all the way back more than 20 years: Should we be doing radical upfront surgery in advanced ovarian cancer, or should we be doing neoadjuvant chemotherapy? So, there was a lot of hype about the TRUST study, also called ENGOT ov33/AGO-OVAR OP7, a Phase 3 randomized study that compares upfront surgery with neoadjuvant chemotherapy followed by interval surgery. So, I want to talk about that study today. And joining me for the discussion is Dr. Kathleen Moore, a professor also of obstetrics and gynecology at the University of Oklahoma and the deputy director of the Stephenson Cancer Center, also at the University of Oklahoma Health Sciences.  Dr. Moore, it is so great to be speaking with you today. Thanks for doing this. Dr. Kathleen Moore: Yeah, it's fun to be here. This is going to be fun. Dr. Linda Duska: FYI for our listeners, both of our full disclosures are available in the transcript of this episode.  So let's just jump right in. We already alluded to the fact that the TRUST study addresses a question we have been grappling with in our field. Here's the thing, we have four prior randomized trials on this exact same topic. So, share with me why we needed another one and what maybe was different about this one? Dr. Kathleen Moore: That is, I think, the key question. So we have to level-set kind of our history. Let's start with, why is this even a question? Like, why are we even talking about this today? When we are taking care of a patient with newly diagnosed ovarian cancer, the aim of surgery in advanced ovarian cancer ideally is to prolong a patient's likelihood of disease-free survival, or if you want to use the term "remission," you can use the term "remission." And I think we can all agree that our objective is to improve overall survival in a way that also does not compromise her quality of life through surgical complications, which can have a big effect. The standard for many decades, certainly my entire career, which is now over 20 years, has been to pursue what we call primary cytoreductive surgery, meaning you get a diagnosis and we go right to the operating room with a goal of achieving what we call "no gross residual." That is very different – in the olden days, you would say "optimal" and get down to some predefined small amount of tumor. Now, the goal is you remove everything you can see.  The alternative strategy to that is neoadjuvant chemotherapy followed by interval cytoreductive surgery, and that has been the, quote-unquote, "safer" route because you chemically cytoreduce the cancer, and so, the resulting surgery, I will tell you, is not necessarily easy at all. It can still be very radical surgeries, but they tend to be less radical, less need for bowel resections, splenectomy, radical procedures, and in a short-term look, would be considered safer from a postoperative consideration. Dr. Linda Duska: Well, and also maybe more likely to be successful, right? Because there's less disease, maybe, theoretically. Dr. Kathleen Moore: More likely to be successful in getting to no gross residual. Dr. Linda Duska: Right. Yeah, exactly. Dr. Kathleen Moore: I agree with that. And so, so if the end game, regardless of timing, is you get to no gross residual and you help a patient and there's no difference in overall survival, then it's a no-brainer. We would not be having this conversation. But there remains a question around, while it may be more likely to get to no gross residual, it may be, and I think we can all agree, a less radical, safer surgery, do you lose survival in the long term by this approach? This has become an increasing concern because of the increase in rates of use of neoadjuvant, not only in this country, but abroad. And so, you mentioned the four prior studies. We will not be able to go through them completely. Dr. Linda Duska: Let's talk about the two modern ones, the two from 2020 because neither one of them showed a difference in overall survival, which I think we can agree is, at the end of the day, yes, PFS would be great, but OS is what we're looking for. Dr. Kathleen Moore: OS is definitely what we're looking for. I do think a marked improvement in PFS, like a real prolongation in disease-free survival, for me would be also enough. A modest improvement does not really cut it, but if you are really, really prolonging PFS, you should see that-  Dr. Linda Duska: -manifest in OS. Dr. Kathleen Moore: Yeah, yeah. Okay. So let's talk about the two modern ones. The older ones are EORTC and CHORUS, which I think we've talked about. The two more modern ones are SCORPION and JCOG0602. So, SCORPION was interesting. SCORPION was a very small study, though. So one could say it's underpowered. 170 patients. And they looked at only patients that were incredibly high risk. So, they had to have a Fagotti score, I believe, of over 9, but they were not looking at just low volume disease. Like, those patients were not enrolled in SCORPION. It was patients where you really were questioning, "Should I go to the OR or should I do neoadjuvant? Like, what's the better thing?" It is easy when it's low volume. You're like, "We're going." These were the patients who were like, "Hm, you know, what should I do?" High volume. Patients were young, about 55. The criticism of the older studies, there are many criticisms, but one of them is that, the criticism that is lobbied is that they did not really try. Whatever surgery you got, they did not really try with median operative times of 180 minutes for primary cytoreduction, 120 for neoadjuvant. Like, you and I both know, if you're in a big primary debulking, you're there all day. It's 6 hours. Dr. Linda Duska: Right, and there was no quality control for those studies, either. Dr. Kathleen Moore: No quality control. So, SCORPION, they went 451-minute median for surgery. Like, they really went for it versus four hours and then 253 for the interval, 4 hours. They really went for it on both arms. Complete gross resection was achieved in 50% of the primary cytoreduced. So even though they went for it with these very long surgeries, they only got to the goal half the time. It was almost 80% in the interval group. So they were more successful there. And there was absolutely no difference in PFS or OS. They were right about 15 months PFS, right about 40 months OS.  JCOG0602, of course, done in Japan, a big study, 300 patients, a little bit older population. Surprisingly more stage IV disease in this study than were in SCORPION. SCORPION did not have a lot of stage IV, despite being very bulky tumors. So a third of patients were stage IV. They also had relatively shorter operative times, I would say, 240 minutes for primary, 302 for interval. So still kind of short. Complete gross resection was not achieved very often. 30% of primary cytoreduction. That is not acceptable. Dr. Linda Duska: Well, so let's talk about TRUST. What was different about TRUST? Why was this an important study for us to see? Dr. Kathleen Moore: So the criticism of all of these, and I am not trying to throw shade at anyone, but the criticism of all of these is if you are putting surgery to the test, you are putting the surgeon to the test. And you are assuming that all surgeons are trained equally and are willing to do what it takes to get someone to no gross residual. Dr. Linda Duska: And are in a center that can support the post-op care for those patients. Dr. Kathleen Moore: Which can be ICU care, prolonged time. Absolutely. So when you just open these broadly, you're assuming everyone has the surgical skills and is comfortable doing that and has backup. Everybody has an ICU. Everyone has a blood bank, and you are willing to do that. And that assumption could be wrong. And so what TRUST said is, "Okay, we are only going to open this at centers that have shown they can achieve a certain level of primary cytoreduction to no gross residual disease." And so there was quality criteria. It was based on – it was mostly a European study – so ESGO criteria were used to only allow certified centers to participate. They had to have a surgical volume of over 36 cytoreductive surgeries per year. So you could not be a low volume surgeon. Your complete resection rates that were reported had to be greater than 50% in the upfront setting. I told you on the JCOG, it was 30%. Dr. Linda Duska: Right. So these were the best of the best. This was the best possible surgical situation you could put these patients in, right? Dr. Kathleen Moore: Absolutely. And you support all the things so you could mitigate postoperative complications as well. Dr. Linda Duska: So we are asking the question now again in the ideal situation, right? Dr. Kathleen Moore: Right. Dr. Linda Duska: Which, we can talk about, may or may not be generalizable to real life, but that's a separate issue because we certainly don't have those conditions everywhere where people get cared for with ovarian cancer. But how would you interpret the results of this study? Did it show us anything different? Dr. Kathleen Moore: I am going to say how we should interpret it and then what I am thinking about. It is a negative study. It was designed to show improvement in overall survival in these ideal settings in patients with FIGO stage IIIB and C, they excluded A, these low volume tumors that should absolutely be getting surgery. So FIGO stage IIIB and C and IVA and B that were fit enough to undergo radical surgery randomized to primary cytoreduction or neoadjuvant with interval, and were all given the correct chemo. Dr. Linda Duska: And they were allowed bevacizumab and PARP, also. They could have bevacizumab and PARP. Dr. Kathleen Moore: They were allowed bevacizumab and PARP. Not many of them got PARP, but it was distributed equally, so that would not be a confounder. And so that was important. Overall survival is the endpoint. It was a big study. You know, it was almost 600 patients. So appropriately powered. So let's look at what they reported. When they looked at the patients who were enrolled, this is a large study, almost 600 patients, 345 in the primary cytoreductive arm and 343 in the neoadjuvant arm. Complete resection in these patients was 70% in the primary cytoreductive arm and 85% in the neoadjuvant arm. So in both arms, it was very high. So your selection of site and surgeon worked. You got people to their optimal outcome. So that is very different than any other study that has been reported to date. But what we saw when we looked at overall survival was no statistical difference. The median was, and I know we do not like to talk about medians, but the median in the primary cytoreductive arm was 54 months versus 48 months in the neoadjuvant arm with a hazard ratio of 0.89 and, of course, the confidence interval crossed one. So this is not statistically significant. And that was the primary endpoint. Dr. Linda Duska: I know you are getting to this. They did look at PFS, and that was statistically significant, but to your point about what are we looking for for a reasonable PFS difference? It was about two months difference. When I think about this study, and I know you are coming to this, what I thought was most interesting about this trial, besides the fact that the OS, the primary endpoint was negative, was the subgroup analyses that they did. And, of course, these are hypothesis-generating only. But if you look at, for example, specifically only the stage III group, that group did seem to potentially, again, hypothesis generating, but they did seem to benefit from upfront surgery.  And then one other thing that I want to touch on before we run out of time is, do we think it matters if the patient is BRCA germline positive? Do we think it matters if there is something in particular about that patient from a biomarker standpoint that is different? I am hopeful that more data will be coming out of this study that will help inform this. Of course, unpowered, hypothesis-generating only, but it's just really interesting. What do you think of their subset analysis? Dr. Kathleen Moore: Yeah, I think the subsets are what we are going to be talking about, but we have to emphasize that this was a negative trial as designed. Dr. Linda Duska: Absolutely. Yes. Dr. Kathleen Moore: So we cannot be apologists and be like, "But this or that." It was a negative trial as designed. Now, I am a human and a clinician, and I want what is best for my patients. So I am going to, like, go down the path of subset analyses. So if you look at the stage III tumors that got complete cytoreduction, which was 70% of the cases, your PFS was almost 28 months versus 21.8 months. Dr. Linda Duska: Yes, it becomes more significant. Dr. Kathleen Moore: Yeah, that hazard ratio is 0.69. Again, it is a subset. So even though the P value here is statistically significant, it actually should not have a P value because it is an exploratory analysis. So we have to be very careful. But the hazard ratio is 0.69. So the hypothesis is in this setting, if you're stage III and you go for it and you get someone to no gross residual versus an interval cytoreduction, you could potentially have a 31% reduction in the rate of progression for that patient who got primary cytoreduction. And you see a similar trend in the stage III patients, if you look at overall survival, although the post-progression survival is so long, it's a little bit narrow of a margin.  But I do think there are some nuggets here that, one of our colleagues who is really one of the experts in surgical studies, Dr. Mario Leitao, posted this on X, and I think it really resonated after this because we were all saying, "But what about the subsets?" He is like, "It's a negative study." But at the end of the day, you are going to sit with your patient. The patient should be seen by a GYN oncologist or surgical oncologist with specialty in cytoreduction and a medical oncologist, you know, if that person does not give chemo, and the decision should be made about what to do for that individual patient in that setting. Dr. Linda Duska: Agreed. And along those lines, if you look carefully at their data, the patients who had an upfront cytoreduction had almost twice the risk of having a stoma than the patients who had an interval cytoreduction. And they also had a higher risk of needing to have a bowel resection. The numbers were small, but still, when you look at the surgical complications, as you've already said, they're higher in the upfront group than they are in the interval group. That needs to be taken into account as well when counseling a patient, right? When you have a patient in front of you who says to you, "Dr. Moore, you can take out whatever you want, but whatever you do, don't make me a bag." As long as the patient understands what that means and what they're asking us to do, I think that we need to think about that. Dr. Kathleen Moore: I think that is a great point. And I have definitely seen in our practice, patients who say, "I absolutely would not want an ostomy. It's a nonstarter for me." And we do make different decisions. And you have to just say, "That's the decision we've made," and you kind of move on, and you can't look back and say, "Well, I wish I would have, could have, should have done something else." That is what the patient wants. Ultimately, that patient, her family, autonomous beings, they need to be fully counseled, and you need to counsel that patient as to the site that you are in, her volume of disease, and what you think you can achieve. In my opinion, a patient with stage III cancer who you have the site and the capabilities to get to no gross residual should go to the OR first. That is what I believe. I do not anymore think that for stage IV. I think that this is pretty convincing to me that that is probably a harmful thing. However, I want you to react to this. I think I am going to be a little unpopular in saying this, but for me, one of the biggest take-homes from TRUST was that whether or not, and we can talk about the subsets and the stage III looked better, and I think it did, but both groups did really well. Like, really well. And these were patients with large volume disease. This was not cherry-picked small volume stage IIIs that you could have done an optimal just by doing a hysterectomy. You know, these were patients that needed radical surgery. And both did well. And so what it speaks to me is that anytime you are going to operate on someone with ovary, whether it be frontline, whether it be a primary or interval, you need a high-volume surgeon. That is what I think this means to me. Like, I would want high volume surgeon at a center that could do these surgeries, getting that patient, my family member, me, to no gross residual. That is important. And you and I are both in training centers. I think we ought to take a really strong look at, are we preparing people to do the surgeries that are necessary to get someone to no gross residual 70% and 85% of the time? Dr. Linda Duska: We are going to run out of time, but I want to address that and ask you a provocative question. So, I completely agree with what you said, that surgery is important. But I also think one of the reasons these patients in this study did so well is because all of the incredible new therapies that we have for patients. Because OS is not just about surgery. It is about surgery, but it is also about all of the amazing new therapies we have that you and others have helped us to get through clinical research. And so, how much of that do you think, like, for example, if you look at the PFS and OS rates from CHORUS and EORTC, I get it that they're, that they're not the same. It's different patients, different populations, can't do cross-trial comparisons. But the OS, as you said, in this study was 54 months and 48 months, which is, compared to 2010, we're doing much, much better. It is not just the surgery, it is also all the amazing treatment options we have for these patients, including PARP, including MIRV, including lots of other new therapies. How do you fit that into thinking about all of this? Dr. Kathleen Moore: I do think we are seeing, and we know this just from epidemiologic data that the prevalence of ovarian cancer in many of the countries where the study was done is increasing, despite a decrease in incidence. And why is that? Because people are living longer. Dr. Linda Duska: People are living longer, yeah. Dr. Kathleen Moore: Which is phenomenal. That is what we want. And we do have, I think, better supportive care now. PARP inhibitors in the frontline, which not many of these patients had. Now some of them, this is mainly in Europe, will have gotten them in the first maintenance setting, and I do think that impacts outcome. We do not have that data yet, you know, to kind of see what, I would be really interested to see. We do not do this well because in ovarian cancer, post-progression survival can be so long, we do not do well of tracking what people get when they come off a clinical trial to see how that could impact – you know, how many of them got another surgery? How many of them got a PARP? I think this group probably missed the ADC wave for the most part, because this, mirvetuximab is just very recently available in Europe. Dr. Linda Duska: Unless they were on trial. Dr. Kathleen Moore: Unless they were on trial. But I mean, I think we will have to see. 600 patients, I would bet a lot of them missed the ADC wave. So, I do not know that we can say we know what drove these phenomenal – these are some of the best curves we've seen outside of BRCA. And then coming back to your point about the BRCA population here, that is a really critical question that I do not know that we're ever going to answer. There have been hypotheses around a tumor that is driven by BRCA, if you surgically cytoreduced it, and then chemically cytoreduced it with chemo, and so you're starting PARP with nothing visible and likely still homogeneous clones. Is that the group we cured? And then if you give chemo first before surgery, it allows more rapid development of heterogeneity and more clonal evolution that those are patients who are less likely to be cured, even if they do get cytoreduced to nothing at interval with use of PARP inhibitor in the front line. That is a question that many have brought up as something we would like to understand better. Like, if you are BRCA, should you always just go for it or not? I do not know that we're ever going to really get to that. We are trying to look at some of the other studies and just see if you got neoadjuvant and you had BRCA, was anyone cured? I think that is a question on SOLO1 I would like to know the answer to, and I don't yet, that may help us get to that. But that's sort of something we do think about. You should have a fair number of them in TRUST. It wasn't a stratification factor, as I remember. Dr. Linda Duska: No, it wasn't. They stratified by center, age, and ECOG status Dr. Kathleen Moore: So you would hope with randomization that you would have an equal number in each arm. And they may be able to pull that out and do a very exploratory look. But I would be interested to see just completely hypothesis-generating what this looks like for the patients with BRCA, and I hope that they will present that. I know they're busy at work. They have translational work. They have a lot pending with TRUST. It's an incredibly rich resource that I think is going to teach us a lot, and I am excited to see what they do next. Dr. Linda Duska: So, outside of TRUST, we are out of time. I just want to give you a moment if there were any other messages that you want to share with our listeners before we wrap up. Dr. Kathleen Moore: It's an exciting time to be in GYN oncology. For so long, it was just chemo, and then the PARP inhibitors nudged us along quite a bit. We did move more patients, I believe, to the cure fraction. When we ultimately see OS, I think we'll be able to say that definitively, and that is exciting. But, you know, that is the minority of our patients. And while HRD positive benefits tremendously from PARP, I am not as sure we've moved as many to the cure fraction. Time will tell. But 50% of our patients have these tumors that are less HRD. They have a worse prognosis. I think we can say that and recur more quickly. And so the advent of these antibody-drug conjugates, and we could name 20 of them in development in GYN right now, targeting tumor-associated antigens because we're not really driven by mutations other than BRCA. We do not have a lot of things to come after. We're not lung cancer. We are not breast cancer. But we do have a lot of proteins on the surface of our cancers, and we are finally able to leverage that with some very active regimens. And we're in the early phases, I would say, of really understanding how best to use those, how best to position them, and which one to select for whom in a setting where there is going to be obvious overlap of the targets. So we're going to be really working this problem. It is a good problem. A lot of drugs that work pretty well. How do you individualize for a patient, the patient in front of you with three different markers? How do you optimize it? Where do you put them to really prolong survival? And then we finally have cell surface. We saw at ASCO, CDK2 come into play here for the first time, we've got a cell cycle inhibitor. We've been working on WEE1 and ATR for a long time. CDK2s may hit. Response rates were respectable in a resistant population that was cyclin E overexpressing. We've been working on that biomarker for a long time with a toxicity profile that was surprisingly clean, which I like to see for our patients. So that is a different platform. I think we have got bispecifics on the rise. So there is a pipeline of things behind the ADCs, which is important because we need more than one thing, that makes me feel like in the future, I am probably not going to be using doxil ever for platinum-resistant disease. So, I am going to be excited to retire some of those things. We will say, "Remember when we used to use doxil for platinum-resistant disease?" Dr. Linda Duska: I will be retired by then, but thanks for that thought. Dr. Kathleen Moore: I will remind you. Dr. Linda Duska: You are right. It is such an incredibly exciting time to be taking care of ovarian cancer patients with all the opportunities.  And I want to thank you for sharing your valuable insights with us on this podcast today and for your great work to advance care for patients with GYN cancers. Dr. Kathleen Moore: Likewise. Thanks for having me. Dr. Linda Duska: And thank you to our listeners for your time today. You will find links to the TRUST study and other 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 to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. More on today's speakers:   Dr. Linda Duska  @Lduska Dr. Kathleen Moore Follow ASCO on social media:     @ASCO on X (formerly Twitter) ASCO on Bluesky   ASCO on Facebook     ASCO on LinkedIn     Disclosures of Potential Conflicts of Interest:    Dr. Linda Duska:   Consulting or Advisory Role: Regeneron, Inovio Pharmaceuticals, Merck, Ellipses Pharma  Research Funding (Inst.): GlaxoSmithKline, Millenium, Bristol-Myers Squibb, Aeterna Zentaris, Novartis, Abbvie, Tesaro, Cerulean Pharma, Aduro Biotech, Advaxis, Ludwig Institute for Cancer Research, Leap Therapeutics  Patents, Royalties, Other Intellectual Property: UptToDate, Editor, British Journal of Ob/Gyn  Dr. Kathleen Moore: Leadership: GOG Partners, NRG Ovarian Committee Chair Honoraria: Astellas Medivation, Clearity Foundation, IDEOlogy Health, Medscape, Great Debates and Updates, OncLive/MJH Life Sciences, MD Outlook, Curio Science, Plexus, University of Florida, University of Arkansas for Medical Sciences, Congress Chanel, BIOPHARM, CEA/CCO, Physician Education Resource (PER), Research to Practice, Med Learning Group, Peerview, Peerview, PeerVoice, CME Outfitters, Virtual Incision Consulting/Advisory Role: Genentech/Roche, Immunogen, AstraZeneca, Merck, Eisai, Verastem/Pharmacyclics, AADi, Caris Life Sciences, Iovance Biotherapeutics, Janssen Oncology, Regeneron, zentalis, Daiichi Sankyo Europe GmbH, BioNTech SE, Immunocore, Seagen, Takeda Science Foundation, Zymeworks, Profound Bio, ADC Therapeutics, Third Arc, Loxo/Lilly, Bristol Myers Squibb Foundation, Tango Therapeutics, Abbvie, T Knife, F Hoffman La Roche, Tubulis GmbH, Clovis Oncology, Kivu, Genmab/Seagen, Kivu, Genmab/Seagen, Whitehawk, OnCusp Therapeutics, Natera, BeiGene, Karyopharm Therapeutics, Day One Biopharmaceuticals, Debiopharm Group, Foundation Medicine, Novocure Research Funding (Inst.): Mersana, GSK/Tesaro, Duality Biologics, Mersana, GSK/Tesaro, Duality Biologics, Merck, Regeneron, Verasatem, AstraZeneca, Immunogen, Daiichi Sankyo/Lilly, Immunocore, Torl Biotherapeutics, Allarity Therapeutics, IDEAYA Biosciences, Zymeworks, Schrodinger Other Relationship (Inst.): GOG Partners

Dr. Pedro Barata and Dr. Aditya Bagrodia discuss the evolving landscape of testicular cancer survivorship, the impact of treatment-related complications, and management strategies to optimize long-term outcomes and quality of life. TRANSCRIPT:  Dr. Pedro Barata: Hello and welcome to By the Book, a podcast series from ASCO that features engaging conversations between editors and authors of the ASCO Educational Book. I'm Dr. Pedro Barata. I'm a medical oncologist at University Hospitals Seidman Cancer Center and associate professor of medicine at Case Western Reserve University in Cleveland, Ohio. I'm also an associate editor of the ASCO Educational Book. We all know that testicular cancer is a rare but highly curable malignancy that mainly affects young men. Multimodal advances in therapy have resulted in excellent cancer specific survival, but testicular cancer survivors face significant long term treatment related toxicities which affect their quality of life and require surveillance and management. With that, I'm very happy today to be joined by Dr. Aditya Bagrodia, a urologic oncologist, professor, and the GU Disease Team lead at UC San Diego[KI1]  Health, and also the lead author of the recently published paper in the ASCO Educational Book titled, "Key Updates in Testicular Cancer: Optimizing Survivorship and Survival." And he's also the host of the world-renowned BackTable Urology Podcast. Dr. Bagrodia, I'm so happy that you're joining us today. Welcome. Dr. Aditya Bagrodia: Thanks, Pedro. Absolutely a pleasure to be here. Really appreciate the opportunity. Dr. Pedro Barata: Absolutely.  So, just to say that our full disclosures are available in the transcript of this episode.  Let's get things started. I'm really excited to talk about this. I'm biased, I do treat testicular cancer among other GU malignancies and so it's a really, really important topic that we face every day, right? Fortunately, for most of these patients, we're able to cure them. But it always comes up the question, "What now? You know, scans, management, cardio oncology, what survivorship programs we have in place? Are we addressing the different survivorship piece, psychology, fertility, et cetera?" So, we'll try to capture all of that today. Aditya, congrats again, you did a fantastic job putting together the insights and thoughts and what we know today about this important topic. And so, let's get focused specifically about what happens when patients get cured. So, many of us, in many centers, were fortunate enough to have these survivorship programs together, but I find that sometimes from talking to colleagues, they're not exactly the same thing and they don't mean the same thing to different people, to different institutions, right? So, first things first. What do you tell a patient perhaps when they ask you, "What can happen to me now that I'm done with treatment for testicular cancer?" Whether it's chemotherapy or just surgery or even radiation therapy? "So, what about the long term? What should I expect, Doctor, that might happen to me in the long run?" Dr. Aditya Bagrodia: Totally. I mean, I think that question's really front and center, Pedro, and really appreciate you all highlighting this topic. It was an absolute honor to work with true thought leaders and the survivorship bit of it is front and center, in my opinion. It's really the focus, you know, we, generally speaking should be able to cure these young men, but it's the 10, 15, 20 years down the way that they're going to largely contend with. The conversation really begins at diagnosis, pre-education. Fortunately, the bulk of patients that present are those with stage one disease, and even very basic things like before orchiectomy, talking about a prosthetic; we know that that can impact body image and self esteem, whether or not they decide to receive it or not. Actually, just being offered a prosthetic is important and this is something, you know, for any urologist, it's kind of critical. To discussing fertility elements to this, taking your time to examine the contralateral testicle, ask about fertility problems, issues, concerns, offer sperm banking, even in the context of a completely normal contralateral testicle, I think these things are quite important.  So if it's somebody with stage one disease, you know, without going too far down discussing adjuvant therapy and so forth, I will start the conversation with, "You know, the testes do largely two things. They make testosterone and they make sperm." By and large, patients are going to be able to have acceptable levels of testosterone, adequate sperm parameters to maintain kind of a normal gonadal state and to naturally conceive, should that be something they're interested in. However, there's still going to be, depending on what resource you look at, somewhere in the order of 10-30% that are going to have issues. Where I think for the stage one patients, it's really incumbent upon us is actually to not wait for them to discuss their concerns, particularly with testosterone, which many times can be a little bit vague, but to proactively ask about it every time. Libido, erectile quality, muscle mass maintenance, energy, fatigue. All of these are kind of associated symptoms of hypogonadism. But for a lot of kids 18-20 years old, it's going to be something insidious that they don't think about. So, for the stage one patients, it absolutely starts with gonadal function. If they are stage two getting surgery, I think the counseling really needs to center around a possibility for ejaculatory dysfunction. Now, for a chemotherapy-naive, nerve-sparing RPLND, generally these days we should be able to preserve ejaculatory function at high volume centers, but you still want to bring that up and again kind of touch base on thinking about sperm banking and so forth before the operation, scars, those are things I think worth talking about, small risk of ascites. Then, I think the intensity of potential long term adverse effects really ramps up when we're talking about systemic therapy, chemotherapy. And then there's of course some radiation therapy specific elements that come up. So, for the chemotherapy bits of it, I really think this is going to be something that can be a complete multi-system affected intervention. So, anxiety, depression, our group has actually shown using some population resources that even suicidality can be increased among patients that have been treated for germ cell tumor. You know, really from the top down, tinnitus, hearing changes, those are things that we need to ask about at every appointment. Neuropathy, sexual health, that we kind of talked about, including ED (erectile dysfunction), vertigo, dizziness, Raynaud's phenomenon, these are kind of more the symptoms that I think we need to inquire about every time. And what we do here and I think at a lot of survivorship programs is use kind of a battery of validated instruments, germ cell tumor specific, platinum treated patient specific. So we use a combination of EORTC questions and PROMIS questions, which actually serves as like a review of systems for the patient, also as a research element. We review that and then depending on what might be going on, we can dig into that further, get them over to colleagues in audiology or psychology, et cetera.  And then of course, screening for the hypertension, hyperlipidemia, metabolic syndrome with basically you or myself or somebody kind of like us serving, many times it's the role of the PCP, just making sure we're checking out, you know, CBC, CMP, et cetera, lipid parameters to screen for those kind of cardiac associated issues along with secondary malignancies. Dr. Pedro Barata: So that's super comprehensive and thorough. Thank you so much. Actually, I love how you break it down in a simple way. Two functions of the testes, produce testosterone and then, you know, the problem related to that is the hypogonadism, and then the second, as you mentioned, produce sperm and of course related to the fertility issues with that.  So, let's start with the first one that you mentioned. So, you do cite that in your paper, around 5-10% of men end up getting, developing hypogonadism, maybe clinical when they present with symptoms, maybe subclinical. So, I'm wondering, for our audience, what kind of recommendations we would give for addressing that or kind of thinking of that? How often are you ordering those tests? And then, when you're thinking about testosterone replacement therapy, is that something you do immediately or are there any guidelines into context that? How do you approach that? Dr. Aditya Bagrodia: So, just a bit more on digging into it even in terms of the questions to ask, you know, "Do you have any decrease in sexual drive? Any erectile dysfunction? Are your morning erections still taking place? Has the ejaculate volume changed? Physically, muscle mass, strength? Have you been putting on weight? Have you noticed increase in body fat?" And sometimes this is complicated because there's some anxiety that comes along with a cancer diagnosis when you're 20, 30 years old, multifactorial, hair loss, hot flashes, irritability. Sometimes they'll, you know, literally they'll say, "You know, my significant other or partners noticed that I'm really just a little bit labile." So I think, you know, there's the symptoms and then checking, usually kind of a gonadal panel, FSH, LH, free and total testosterone, sex hormone binding globulin, that's going to be typically pretty comprehensive. So if you've got symptoms plus some laboratory work, and ideally that pre-orchiectomy testosterone gives you some delta. If they started out at an 800, 900, now they're 400, that might be a big change for them. And then, when you talk about TRT (Testosterone Replacement Therapy) recommendations, you know, Pedro, yourself, myself, we're kind of lucky to be at academic centers and we've got men's health colleagues that are ultra experts, but at a high level, I would say that a lot of the TRT options center around fertility goals. Exogenous testosterone treats the low T, but it does suppress gonadal function, including spermatogenesis. So if that's not a priority, they can just get TRT. It should be done under the care of a urologist, a men's health, an endocrinologist, where we're checking liver chemistries and CBCs and a PSA and so forth. If they're interested in fertility preservation, then I would say engaging an endocrinologist, men's health expert is important. There's medications even like hCG, Clomid, which works centrally and stimulate the gonadal access. Niche scenarios where they might want standard TRT now, and then down the way, 5, 7 years, they're thinking about coming off of that for fertility purposes, I think that's really where you want to have an expert involved because there's quite a bit of nuance there in recovery of actual spermatogenesis and so forth.  To kind of summarize, you got to ask about it. Checking it is, is not overly complicated. We do a baseline pre-orchiectomy and at least once annually, you can tag it in with the tumor markers, so it's not an extra blood draw. And if they have symptoms of course, kind of developed, then we'll move that up in the evaluation. Dr. Pedro Barata: Got it. And you also touch base on the fertility angle, which is truly important. And I'm just curious, you know, a lot of times many of us might see one, two patients a year, right, and we forget these protocols and what we've got to do about that.  And so I'm interested to hear your thoughts about when you think about fertility, and how proactive you get. In other words, who do you refer for the fertility clinic, for a fertility preservation program? You know, do all cases despite getting through orchiectomy or just the cases that you're going to, you know you're going to seek chemotherapy at some point? What kind of selection or it depends on the chemo, like how do you do that assessment about the referral for preservation program that you might have available at UCSD? Dr. Aditya Bagrodia: Yeah, I mean I feel really fortunate to sit on the NCCN Testis Cancer Guidelines. It's in there that fertility counseling should be discussed prior to orchiectomy. So 100% bring it up. If there are risk factors, undescended testicles, previous history of fertility concerns, atrophic contralateral testicle, anything on the ultrasound like microlithiasis in the contralateral testicle, you kind of wanna get it there. And then again, there's kind of niche scenarios where you're really worried, maybe get a semen analysis and it doesn't look that good, arrange for the time of orchiectomy to have onco-testicular sperm extraction from the, quote unquote, "normal" testis parenchyma. You know, I think you have to be kind of prepared to go that route and really make sure you're doing this completely comprehensively.  So pre-orchiectomy all patients. Don't really push for it too hard if they've got a contralateral testicle, if they've had no issues having children. There's some cost associated with this, sperm banking still isn't kind of covered even in the context of men with cancer. If they've got risk factors, absolutely pre-orchiectomy. Pre-RPLND, even though the rates of ejaculatory dysfunction at a high-volume center should be low single digits, I'll still offer it. That'd be a real catastrophe if they were in that small proportion of patients and now they're going to be reliant on things like intrauterine insemination, where it becomes quite expensive.  Pre-chemo, everybody. That's basically a standard these days where it should be discussed and it's kind of amazing currently, even if you don't have an accessible men's health fertility clinic, there are actually companies, I have no vested interest, Fellow is one such company where you can actually create an account, receive a FedEx semen analysis and cryopreservation kit, send it back in, and all CLIA certified, it's based out of California. The gentleman that runs it, is a urologist and very, very bright guy who's done a lot of great stuff for testis cancer. So, even for patients that are kind of in extremis at the hospital that kind of need to get going like yesterday, we still discuss it. We've got some mechanisms in place to either have them take a semen analysis over to our Men's Health clinic or send it off to Fellow, which I think is pretty cool and that even extends to some of our younger adolescent patients where going to a clinic and providing a sample might be tricky.  So, I think bringing it up every stage, anytime there's an intervention that might be offered, orchiectomy, chemo, surgery, radiation, it's kind of incumbent on us to discuss it. Dr. Pedro Barata: Gotcha. That's super helpful. And you also touch base on another angle, which is the psychosocial angle around this. You mentioned suicidal rates, you mentioned anxiety, perhaps depression in some cases as well as chronic fatigue, not necessarily just because of the low testosterone that you can get, but also from a psychological perspective. I'm curious, what do the recommendations look like for that? Do these patients need to see a social worker or a psychologist, or do they need to answer a screening test every time they come to see us and then based on that, we kind of escalate, take the next steps according to that? Do they see a psychologist perhaps every so often? How should that be managed and addressed? Dr. Aditya Bagrodia: It's an excellent question and again, these can be rather insidious symptoms where if you don't really dig in and inquire, they can be glossed over. I mean, how easy to say, "Your markers look okay, your scans look okay. See you in six months," and keep it kind of brief. First off, I think bringing it up proactively and normalizing it, that, "This may be something that you experience. Many people do, you're not alone, there's nothing kind of wrong with you." I also think that this is an area where support groups can be incredibly useful. We host the Testicular Cancer Awareness Foundation support group here. They'll talk about chemo brain or just like a little bit of an adjustment disorder after their diagnosis. Support groups, I think are critical. As I mentioned, we have a survivorship program that's led by a combination of our med oncs, myself on the uro-onc side, as well as APPs, where we are systematically asking about essentially the whole litany of issues that may arise, including psychosocial, anxiety, depression, suicidality. And we've got a nice kind of fast path into our cancer center support services for these young men to meet with a psychologist. If that isn't going to be sufficient, they can actually see a psychiatrist to discuss medications and so forth. I do think that we've got to screen for these because, as anticipated from diagnosis, those first 2 years, we see a rise. But even 10, 15 years out, we note, compared to controls, that there is an increased level of anxiety, depression, suicidality that might not just take place at that initial acute period of diagnosis and treatment. Dr. Pedro Barata: Really well said. Super important.  So I guess if I were to put all these together, with these really amazing advances in technology, we all know AI, some of us might be more or less aware of biomarkers coming up, including microRNA for example, and others, like as I think of all these potential long term complications for these patients, look at the future, I guess, can we use this as a way to deescalate treatment where it's not really necessary, as a way to actually prevent some of these complications? Like, how do we see where we're heading? As we manage testicular cancer, let's say, within the next 5 or 10 years, do you think there's something coming up that's going to be different from what we're doing things today? Dr. Aditya Bagrodia: Totally. I mean, I think it's as exciting as a time as there's ever been, you know, maybe notwithstanding circa 1970s when platinum was discovered. So microRNAs, which you mentioned, you know, there's a new candidate biomarker, microRNA-371. We are super excited here at UCSD. We actually have it CLIA-certified available in our lab and are ordering these tests for patients kind of in their acute stage, you know, stage one and surveillance, stage two, post-RPLND, receiving chemotherapy. And essentially this is a universal germ cell tumor specific biomarker, except for teratoma, suffice it to say 90% sensitive and specific. And I think it's going to change the way that we diagnose and manage patients. You know, pre-orchiectomy, that's pretty straightforward. Post-orchiectomy, maybe we can really decrease the number of CT scans that are done. Maybe we can identify those patients that basically have occult disease where we can intervene early, either with RPLND or single cycle chemo. Post-RPLND, identify the patients who are at higher risk of relapse that may benefit from some adjuvant therapy. In the advanced setting, look at marker decline for patients in addition to standard tumor markers. Can we modulate their systemic therapy?  So, the international interest is largely on modifying things. There's really cool clinical trials that we have for stage one patients, that treatment would be prescribed based on a post-orchiectomy microRNA. I think the microRNAs are really exciting. Teratoma remains an outstanding question. I think this is where maybe ctDNA, perhaps some radiomics and advanced imaging processing and incorporating AI may allow us to safely avoid a lot of these post-chemo RPLNDs. And then identification using SNPs and so forth of who might be most susceptible to some of the cardiac toxicity, autotoxicity and personalizing things in that way as well. Dr. Pedro Barata: Super exciting, right, what's about to come? And I agree with you, I think it's going to change dramatically how we manage this disease.  This has been a pleasure sitting down with you. I guess before letting you go, anything else you'd like to add before we wrap it up? Dr. Aditya Bagrodia: Yeah, first off, again, just want to thank you and ASCO for the opportunity. And it's easy enough to, I think, approach a patient with the testicular germ cell tumor as, "This is an easy case. We're just going to do whatever we've done. Go to the guidelines that says do X, Y, or Z." But there's so much more nuance to it than that. Getting it done perfectly, I think, is mandatory. Whatever we do is an impact on them for the next 50, 60, 70 years of their life. And I found the germ cell tumor community, people are really passionate about it. If you're ever uncertain, there's experts throughout the country and internationally. Ask somebody before you do something that you can't undo. I think we owe it to them to get it perfect so that we can really maximize the survivorship and the survival like we've been talking about. Dr. Pedro Barata: Aditya, thanks for sharing your fantastic insights with us on this podcast. Dr. Aditya Bagrodia: All right, Pedro. Fantastic. Appreciate the opportunity. Dr. Pedro Barata: And also, thank you to our listeners for your time today. I actually encourage you to check out Dr. Bagrodia's article in the 2025 ASCO Educational Book. We'll post a link to the paper in the show notes. Remember, it's free access online, and you can actually download it as well as a PDF. You can also find on the website a wealth of other great papers from the ASCO Educational Book on key advances and novel approaches that are shaping modern oncology.  So with that, thank you everyone. Thank you, Aditya, one more time, for joining us. Thank you, have a good day. 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. Pedro Barata  @PBarataMD   Dr. Aditya Bagrodia @AdityaBagrodia Follow ASCO on social media:         @ASCO on X (formerly Twitter)         ASCO on Bluesky        ASCO on Facebook         ASCO on LinkedIn         Disclosures:      Dr. Pedro Barata:  Stock and Other Ownership Interests: Luminate Medical  Honoraria: UroToday  Consulting or Advisory Role: Bayer, BMS, Pfizer, EMD Serono, Eisai, Caris Life Sciences, AstraZeneca, Exelixis, AVEO, Merck, Ipson, Astellas Medivation, Novartis, Dendreon  Speakers' Bureau: AstraZeneca, Merck, Caris Life Sciences, Bayer, Pfizer/Astellas  Research Funding (Inst.): Exelixis, Blue Earth, AVEO, Pfizer, Merck   Dr. Aditya Bagrodia: Consulting or Advisory Role: Veracyte, Ferring  

Many of the top stories of 2025 are currently being written. We're on the edge of our keyboards, watching and waiting as Pfizer and Novo Nordisk duke it out over the right to acquire glittery obesity startup Metsera. In the latest development, Pfizer raised its original bid of around $7.27 billion to about $8.1 billion on Monday—only to be usurped again by the indefatigable Novo, which upped its own bid to a cool $10 billion.  Meanwhile, the unprecedented drama in the uppermost ranks of the FDA—another top story of 2025—continues as CDER Director George Tidmarsh exits the agency. Tidmarsh reportedly resigned Sunday after being placed on administrative leave amid an investigation into his “personal conduct” at the agency. On Monday, however, Tidmarsh told Endpoints News that he was “second-guessing” his decision.  Speaking of the FDA, the regulator appears to have done its own 180—on uniQure's investigational gene therapy for Huntington's disease, three-year data from which sent the biotech's stock into the stratosphere just five weeks ago. Despite previous agreements on protocols and statistical analyses, the agency “no longer agrees” that Phase I/II data for AMT-130 are adequate to provide primary evidence for the application, uniQure said, throwing the timeline for the BLA into question.  Another gene therapy player, Sarepta Therapeutics, took a hit this week, as two of its Duchenne muscular dystrophy drugs, Vyondys 53 and Amondys 45, failed a confirmatory trial. Sarepta still plans to file for full approval of the two exon-skipping therapies, however, based on what it called “encouraging trends” in efficacy. Finally, on the genetic medicine front, CBER director Vinay Prasad teased an upcoming paper that will detail the regulator's thinking and a new approach to gene editing approvals.  On top of all that, Q3 earnings continue to roll in, with Pfizer, Eli Lilly, Vertex, Bristol Myers Squibb, AbbVie, and more reporting results.  One more thing: Have you ever wanted to know more about the inner workings of the Biogen-Eisai Alzheimer's partnership? Check out this profile on BioSpace 40 under 40 honoree Neena Bitritto-Garg, Eisai alum and current CEO of Ensho Therapeutics. 

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we're exploring a series of significant developments that underscore the rapid evolution within these industries.Starting with one of the major players, Merck, which has been strategically adjusting its focus in light of Keytruda's looming loss of exclusivity. The company has demonstrated remarkable progress with Welireg in kidney cancer trials, successfully pairing it with Keytruda. This combination therapy is a beacon of hope for Merck as it faces the challenges of patent expiration, highlighting the growing trend toward leveraging combination treatments to enhance efficacy in cancer therapies. This approach not only pushes the boundaries of cancer treatment but also paves the way for future therapeutic innovations. In contrast, Merck and Eisai have decided to cease their pursuit of a Keytruda-Lenvima pairing for a specific liver cancer subtype after failing to achieve overall survival benefits, despite earlier progress-free survival gains. Such developments highlight the inherent uncertainties in oncology drug development, where initial promising results may not always lead to long-term survival advantages.Meanwhile, Eli Lilly is making headlines with its substantial $1.2 billion investment to upgrade its Puerto Rico manufacturing facility. This move is aligned with their strategy to amplify production capabilities for oral drugs, particularly focusing on their promising GLP-1 pill, Orforglipron. The investment signifies a robust commitment to addressing diabetes and potentially other metabolic disorders through an expanded and more efficient production pipeline. Additionally, Eli Lilly's collaboration with NVIDIA aims at constructing an unprecedented supercomputer tailored for pharmaceutical research. This initiative leverages advanced computational power to accelerate drug discovery processes and enhance data analysis capabilities—a testament to how AI and machine learning are streamlining research workflows for developing more effective therapeutics.On the regulatory stage, Akebia Therapeutics has opted to cancel a trial for its anemia drug Vafseo after discussions with the FDA. This decision sheds light on the intricate challenges companies encounter while navigating regulatory landscapes and optimizing clinical trial strategies to ensure market success.In legal news, Kenvue is preparing for a lawsuit filed by Texas Attorney General Ken Paxton regarding alleged deceptive marketing practices about Tylenol's safety during pregnancy and its purported link to autism risk. This case emphasizes the necessity for pharmaceutical companies to uphold rigorous scientific evidence supporting their marketing claims while navigating potential legal challenges.Strategically, WuXi AppTec's decision to divest its China-based clinical research units marks a broader industry trend of streamlining operations to concentrate on core competencies. By focusing resources on its Contract Research Development and Manufacturing Organization (CRDMO) platform, WuXi aims to leverage growth opportunities in this burgeoning sector.In a notable technological partnership, Johnson & Johnson's medical technology division and Verily have entered agreements with NVIDIA, highlighting the increasing intersection of artificial intelligence with life sciences. These collaborations are poised to advance AI applications within healthcare, potentially transforming areas such as data analysis, diagnostics, and personalized medicine.The industry is also feeling the impact of governmental actions, as evidenced by a federal government shutdown starting October 1st that has led to indefinite blocks on federal worker firings. Such political developments can significantly affect healthcare funding and policymaking processes.These stories collectively paint a piSupport the show

Live from Berlin, Germany, Dr. Aly-Khan Lalani and Dr. Christopher Wallis review the major ESMO 2025 prostate cancer studies, including ENZARAD, EMBARK, CAPItello-291, PSMAddition, and PR21. Together, they unpack their clinical impact and how evolving biomarkers, imaging, and treatment sequencing are redefining standards of care.The View on GU with Lalani & Wallis integrates key clinical data from major conferences and high impact publications, sharing meaningful take home messages for practising clinicians in the field of genitourinary (GU) cancers. Learn more about The View on GU: theviewongu.caThis podcast has been made possible through unrestricted financial support by Novartis, Bayer, Astellas, Tolmar, Ipsen, J&J, Merck, Pfizer, Eisai and AbbVie.

Live from Berlin, Germany, Dr. Aly-Khan Lalani and Dr. Christopher Wallis review ESMO 2025's bladder cancer headlines, from the evolving role of PD-1/PD-L1 inhibitors to ctDNA-guided adjuvant therapy and antibody-drug conjugates redefining metastatic management.The View on GU with Lalani & Wallis integrates key clinical data from major conferences and high impact publications, sharing meaningful take home messages for practising clinicians in the field of genitourinary (GU) cancers. Learn more about The View on GU: theviewongu.caThis podcast has been made possible through unrestricted financial support by Novartis, Bayer, Astellas, Tolmar, Ipsen, J&J, Merck, Pfizer, Eisai and AbbVie.

Wrapping up our live ESMO 2025 coverage from Berlin, Germany, Dr. Aly-Khan Lalani and Dr. Christopher Wallis review pivotal kidney cancer data, including RAMPART's results, emerging first-line combinations from KEYMAKER-U03 and more, offering a forward-looking view of where RCC research is heading next.The View on GU with Lalani & Wallis integrates key clinical data from major conferences and high impact publications, sharing meaningful take home messages for practising clinicians in the field of genitourinary (GU) cancers. Learn more about The View on GU: theviewongu.caThis podcast has been made possible through unrestricted financial support by Novartis, Bayer, Astellas, Tolmar, Ipsen, J&J, Merck, Pfizer, Eisai and AbbVie.

In this episode, Viktor Grünwald shares his journey through a remarkable career in oncology, his focus on urogenital cancers, and his hopes for the future of cancer treatment. From reflections on research to European Society for Medical Oncology (ESMO) 2025 predictions and the promise of precision medicine, Grünwald offers an insightful look at evolving therapies and the pursuit of higher cure rates.  Timestamps:   00:00 – Introduction  01:03 – Reflections on his career  02:06 – Balancing research, clinical duties, and teaching  03:10 – Specialising in urogenital cancers  04:50 – Viktor's hobbies and interests  05:47 – Current landscape of genitourinary cancers  09:09 – Treatment modalities  11:09 – The CLEAR study  12:54 – European Society for Medical Oncology (ESMO) 2025 predictions  15:57 – The potential of precision medicine  19:09 – Viktor's three wishes for healthcare     Disclosure: Grünwald has received honoraria from Bristol Myers Squibb, Ipsen, Eisai, MSD Oncology, Merck Serono, AstraZeneca, Advanced Accelerator Applications (acquired by Novartis), Astellas Pharma, Amgen, Johnson & Johnson/Janssen, Telix Pharmaceuticals, Gilead Sciences, and Roche; research funding from Amgen, MSD Oncology, Bristol Myers Squibb, Seattle Genetics (now Seagen; acquired by Pfizer), Ipsen, Gilead Sciences, Bicycle Therapeutics, Exelixis, Novartis, Roche, and Johnson & Johnson/Janssen, with payment to the institution; travel/accommodation/expenses from Pfizer, Janssen, Merck Serono, Ipsen, and Amgen; and held consulting or advisory roles for Bristol Myers Squibb, Pfizer, Novartis, MSD Oncology, Ipsen, Janssen-Cilag, Eisai, Debiopharm, Gilead Sciences, Oncorena, Synthekine, and Recordati.  The CLEAR study was sponsored Eisai and Merck Sharp & Dohmre. 

Ahead of ESMO 2025 in Germany, Dr. Monty Pal sits down with Dr. Aly-Khan Lalani and Dr. Chris Wallis to discuss what the oncology community can expect to see at this year's Congress. From groundbreaking bladder cancer therapies to the newest approaches in prostate and kidney cancer, this episode explores various abstracts and presentations set to be shared in Berlin. The View on GU with Lalani & Wallis integrates key clinical data from major conferences and high impact publications, sharing meaningful take home messages for practising clinicians in the field of genitourinary (GU) cancers. Learn more about The View on GU: theviewongu.caThis podcast has been made possible through unrestricted financial support by Novartis, Bayer, Astellas, Tolmar, Ipsen, J&J, Merck, Pfizer, Eisai and AbbVie.

Dr. Aly-Khan Lalani and Dr. Christopher Wallis sit down with the Executive Vice-President, Evidence, Products, and Services at Canada's Drug Agency (CDA-AMC), Sudha Kutty. In part one of this series on drug approval, they discuss health technology assessments and frameworks, how CDA-AMC balances timely access with rigorous evidence review and more.The View on GU with Lalani & Wallis integrates key clinical data from major conferences and high impact publications, sharing meaningful take home messages for practising clinicians in the field of genitourinary (GU) cancers. Learn more about The View on GU: theviewongu.caThis podcast has been made possible through unrestricted financial support by Novartis, Bayer, Astellas, Tolmar, Ipsen, J&J, Merck, Pfizer, Eisai and AbbVie.

On The Down Low – Season 2: it's time to start talking about uterine cancersThe body often whispers before it screams — and recognising those early whispers can save lives. In this episode, we explore the importance of listening to symptoms like abnormal bleeding, and the role of risk factors such as obesity, hormones, lifestyle, and genetic predispositions including Lynch Syndrome. Through lived experience stories from Carly and Ruth, and expert insights from Professor Alison Brand AM, we uncover how prevention, risk assessment, and early diagnosis can change the future of uterine cancers.Know someone who needs to hear this? Share it, talk about it, and help break the silence around uterine cancers.Season 2 was produced by ANZGOG, with the generous support of GSK and Eisai.

The high cost associated with cancer diagnosis, treatment, and survivorship makes the burden of financial toxicity an unavoidable reality for many patients—and makes financial navigators central to the delivery of high-quality cancer care. In this vodcast episode, CANCER BUZZ speaks with Heather Simpson, BCPA, patient financial navigator lead, who shares her experience using the ACCC Financial Advocacy Network's financial advocacy services guidelines assessment tool to pinpoint financial navigation challenges within her cancer program. Heather Simpson, BCPA Patient Financial Navigator Lead              Allina Health Cancer Institute   River Falls, WI “When [ACCC] came out with a gap assessment tool in 2024...it allowed us to see where we had hit the mark with our program and where we had some gaps we could take care of to really be in line with the [Financial Advocacy Network's] guidelines.” Resources: Financial Advocacy Guidelines Financial Advocacy Services Assessment Tool Financial Advocacy Services Guidelines Assessment Tool User Guide In the Field: Practical Financial Advocacy Strategies for Supporting Cancer Patients Oncology Reimbursement Meetings This podcast is made possible by funding and support provided by Genentech, Eisai, Pfizer, and Regeneron and in partnership with AONN+, NPAF, Triage Cancer, and CancerCare.  

Dr. Pedro Barata and Dr. Rana McKay discuss the integration of innovative advances in molecular imaging and therapeutics to personalize treatment for patients with renal cell and urothelial carcinomas. TRANSCRIPT Dr. Pedro Barata: Hello, I'm Dr. Pedro Barata, your guest host of By the Book, a podcast series featuring insightful conversations between authors and editors of the ASCO Educational Book. I'm a medical oncologist at University Hospitals Seidman Cancer Center and an associate professor of medicine at Case Western Reserve University in Cleveland, Ohio. I'm also an associate editor of the ASCO Educational Book. Now, we all know the field of genitourinary cancers (GU) is evolving quite rapidly, and we have new innovations in molecular imaging as well as targeted therapeutics. Today's episode will be exploring novel approaches that are transforming the management of renal cell and urothelial carcinomas and also their potential to offer a more personalized treatment to patients. For that, joining for today's discussion is Dr. Rana McKay, a GU medical oncologist and professor at University of California San Diego. Dr. McKay will discuss her recently published article titled, “Emerging Paradigms in Genitourinary Cancers: Integrating Molecular Imaging, Hypoxia-Inducible Factor-Targeted Therapies, and Antibody-Drug Conjugates in Renal Cell and Urothelial Carcinomas.”  Our full disclosures are available in the transcript of this episode.  And with that, Rana McKay, great to have you on the podcast today. Dr. Rana McKay: Oh, thank you so much, Dr. Barata. It's really wonderful to be here with you. So, thanks for hosting. Dr. Pedro Barata: No, thanks for taking the time, and I'm looking forward to this conversation. And by the way, let me start by saying congrats on a great article in the Educational Book. Really super helpful paper. I'm recommending it to a lot of the residents and fellows at my own institution. I would like to first ask you to kind of give our listeners some context of how novel approaches in the molecular imaging as well as targeted therapeutics are actually changing the way we're managing patients with GU, but specifically with renal cell carcinoma and urothelial carcinoma. So, what are the areas you would call out as like being big areas for innovation in this context, and why are they important? Dr. Rana McKay: Very good question. And I think this is really what this article highlights. It highlights where are we going from an imaging diagnostics standpoint? Where are we going from a therapeutic standpoint? And I think if we have to step back, from the standpoint of diagnostics, we've seen PET imaging really transform diagnostics in prostate cancer with the advent of PSMA PET imaging, and now PSMA PET imaging is used as a biomarker for selection for theranostics therapy. And so, we're starting to see that enter into the RCC landscape, enter into the urothelial cancer landscape to a lesser extent. And I think it's going to potentially be transformative as these tools get more refined. I think when we think about therapeutics, what's been transformative most recently in the renal cell carcinoma landscape has been the advent of HIF2α inhibition to improve outcomes for patients. And we have seen the approval of belzutifan most recently that has reshaped the landscape. And now there's other HIF2α inhibitors that are being developed that are going to be further important as they get refined. And lastly, I think when we think about urothelial carcinoma, the greatest transformation to treatment in that context has been the displacement of cisplatin and platinum-based chemotherapy as a frontline standard with the combination of enfortumab vedotin plus pembrolizumab. And we've seen antibody-drug conjugates really reshape treatment and tremendously improve outcomes for patients. So, I think those are the three key areas of interest. Dr. Pedro Barata: So with that, let's focus first on the imaging and then we'll get to the therapeutic area. So, we know there's been a paradigm shift, really, when prostate-specific targets emerged as tracers for PET scanning. And so, we now commonly use prostate-specific membrane antigen, or PSMA-based PET scanning, and really transform how we manage prostate cancer. Now, it appears that we're kind of seeing a similar wave in renal cell carcinoma with the new radiotracer against the target carbonic anhydrase IX. What can you tell us about this? And is this going to be available to us anytime soon? And how do you think that might potentially change the way we're managing patients with RCC today? Dr. Rana McKay: First, I'll step back and say that in the context of PSMA PET imaging, we have actually been able to better understand RCC as well. So, we know that PSMA is expressed in the neovasculature of tumors, and it can actually be used to detect renal cell carcinoma tumors. It has a detection rate of about 84% when used for detection. And so, you know, I don't think it's just restricted to carbonic anhydrase IX, but we will talk about that. So, PSMA expressed in the neovasculature has a detection rate of around 84%, particularly if we're looking at clear cell RCC. CAlX is overexpressed in clear cell RCC, and it's actually used in diagnosing renal cell carcinoma when we think of CAlX IHC for diagnosing clear cell RCC. And now there are CAlX PET tracers. The first foray was with the ZIRCON study that was actually an interestingly designed study because it was designed to detect the likelihood of PET imaging to identify clear cell RCC. So, it was actually used in the early diagnostics setting when somebody presents with a renal mass to discriminate that renal mass from a clear cell versus a non-clear cell, and it was a positive study. But when I think about the potential application for these agents, you know, I think about the entire landscape of renal cell carcinoma. This is a disease that we do treat with metastasis-directed therapy. We have certainly seen patients who've undergone metastasectomy have long, durable remissions from such an approach. And I think if we can detect very early onset oligometastatic disease where a metastasis-directed therapy or SABR could be introduced - obviously tested in a trial to demonstrate its efficacy - I think it could potentially be transformative. Dr. Pedro Barata: Wonderful. It's a great summary, and I should highlight you are involved in some of those ongoing studies testing the performance of this specific PET scanning for RCC against conventional imaging, right? And to remind the listeners, thus far, for the most part, we don't really do FDG-PET for RCC. There are some specific cases we do, but in general, they're not a standard scanning. But maybe that will change in the future. Maybe RCC will have their own PSMA-PET. And to your point, there's also emerging data about the role of PSMA-PET scanning in RCC as well, as you very elegantly summarized. Wonderful. So, let me shift gears a little bit because you did, in your introduction, you did highlight a novel MOA that we have in renal cell carcinoma, approved for use, initially for VHL disease, and after that for sporadic clear cell renal cell carcinoma. We're talking about hypoxia-inducible factor 2-alpha inhibitors, or HIF2α inhibitors, such as belzutifan. But there's also others coming up. So, as a way to kind of summarize that, what can you tell us about this breakthrough in terms of therapeutic class, this MOA that got to our toolbox of options for patients with advanced RCC? Tell us a little bit what is being utilized currently in the management of advanced RCC. And where do you see the future going, as far as, is it moving early on? Is it getting monotherapy versus combinations? Maybe other therapies? What are your thoughts about that? What can you tell us about it? Dr. Rana McKay: Belzutifan is a first-in-class HIF2α inhibitor that really established clinical validation for HIF2α as a therapeutic target. When we think about the activity of this agent, the pivotal LITESPARK-005 trial really led to the approval of belzutifan in patients who were really heavily pretreated. It was patients who had received prior IO therapy, patients who had received prior VEGF-targeted therapy. And in the context of this study, we saw a median PFS of 5.6 months, and there did seem to be a tail on the curve when you looked at the 12-month PFS rate with belzutifan. It was 33.7% compared to 17.6% with everolimus. And then when we look at the response rate, it was higher with belzutifan on the order of 22-23%, and very low with everolimus, as we've previously seen. I think one of the Achilles heels of this regimen is the primary PD rate, which was 34% when used in later line. There are multiple studies that are testing belzutifan in combination across the treatment landscape. So, we have LITESPARK-011, which is looking at the combination of belzutifan plus lenvatinib in the second-line setting. We've got the MK-012 [LITESPARK-012] study, which is looking at belzutifan in various combinations in the frontline setting. So there is a combination with IO plus belzutifan. And so this is also being looked at in that context. And then we also have the LITESPARK-022 study, which is looking at pembrolizumab with belzutifan in the adjuvant setting. So there's a series of studies that will be exploring belzutifan really across the treatment landscape. Many of these studies in combination. Additionally, there are other HIF2α inhibitors that are being developed. We have casdatifan, which is another very potent HIF2α inhibitor. You know, I think pharmacologically, these are different agents. There's a different half-life, different dosing. What is going to be the recommended phase 3 dose for both agents, the EPO suppression levels, the degree of EPO suppression, and sustainability of EPO suppression is very different. So, I think we've seen data from casdatifan from the ARC-20 trial from monotherapy with a respectable response rate, over 30%, primary PD rate hovering just around 10%.  And then we've also seen data of the combination of casdatifan with cabozantinib as well that were recently presented this year. And that agent is also being tested across the spectrum of RCC. It's being looked at in combination with cabozantinib in the PEAK-1 study, and actually just at the KCRS (Kidney Cancer Research Summit), we saw the unveiling of the eVOLVE-RCC trial, which is going to be looking at a volrustomig, which is a PD-1/CTLA-4 inhibitor plus casdatifan compared to nivo-ipi in the frontline setting.  So, we're going to see some competition in this space of the HIF2α inhibitors. I think when we think of mechanism of action in that these are very potent, not a lot of off-target activity, and they target a driver mutation in the disease. And that driver mutation happens very early in the pathogenesis. These are going to be positioned much earlier in the treatment landscape. Dr. Pedro Barata: All these studies, as you're saying, look really promising. And when we talk about them, you mentioned a lot of combinations. And to me, when I think of these agents, it makes a lot of sense to combine because there's not a lot of overlapping toxicities, if you will. But perhaps for some of our listeners, who have not used HIF2α inhibitors in practice yet, and they might be thinking about that, what can you tell us about the safety profile? How do you present it to your patients, and how do you handle things like hypoxia or anemia? How do you walk through the safety profile and tolerability profile of those agents like belzutifan? Dr. Rana McKay: I think these drugs are very different than your traditional TKIs, and they don't cause the classic symptoms that are associated with traditional TKIs that many of us are very familiar with like the rash, hand-foot syndrome, hypertension, diarrhea. And honestly, these are very nuanced symptoms that patients really struggle with the chronicity of being on a chronic daily TKI. The three key side effects that I warn patients about with HIF2α inhibitors are: (1) fatigue; (2) anemia; and (3) hypoxia and dysregulation in the ability to sense oxygen levels. And so, many of these side effects - actually, all of them - are very dose-dependent. They can be very well-managed. So, we can start off with the anemia. I think it's critically important before you even start somebody on belzutifan that you are optimizing their hemoglobin and bone marrow function. Make sure they don't have an underlying iron deficiency anemia. Make sure they don't have B12 or folate deficiency. Check for these parameters. Many patients who have kidney cancer may have some hematuria, other things where there could be some low-level blood loss. So, make sure that those are resolved or you're at least addressing them and supplementing people appropriately. I monitor anemia very closely every 3 to 4 weeks, at least, when people start on these medications. And I do initiate EPO, erythropoietin, should the anemia start to worsen. And I typically use a threshold of around 10g/dL  for implementing utilization of an EPO agent, and that's been done very safely in the context of the early studies and phase 3 studies as well. Now, with regards to the hypoxia, I think it's also important to make sure that you're selecting the appropriate individual for this treatment. People who have underlying COPD, or even those individuals who have just a very high burden of disease in their lung, lymphangitic spread, pleural effusions, maybe they're already on oxygen - that's not an ideal candidate for belzutifan. Something that very easily can be done in the clinic before you think about initiating somebody on this treatment, and has certainly been integrated into some of the trials, is just a 6-minute walk test. You know, have the patient walk around the clinic with one of the MAs, one of the nurses, put the O2 sat on [measuring oxygen saturation], make sure they're doing okay. But these side effects, like I said, are very dose-dependent. Typically, if a patient requires, if the symptoms are severe, the therapy can be discontinued and dose reduced. The standing dose is 120 mg daily, and there's two dose reductions to 80 mg and 40 mg should somebody warrant that dose modification. Dr. Pedro Barata: This is relatively new, right? Like, it was not that we're used to checking oxygen levels, right? In general, we're treating these patients, so I certainly think there's a learning curve there, and some of the points that you highlight are truly critical. And I do share many of those as well in our practice. Since I have you, I want to make sure we touch base on antibody-drug conjugates as well. It's also been a hot area, a lot of developments there. When I think of urothelial carcinoma and renal cell carcinoma, I see it a little bit different. I think perhaps in urothelial carcinoma, antibody-drug conjugates, or ADCs, are somewhat established already. You already mentioned enfortumab vedotin. I might ask you to expand a little bit on that. And then in renal cell carcinoma, we have some ADCs as well that you include in your chapter, and that I would like you to tell us what's coming from that perspective. So, tell us a little bit about how do you see ADCs in general for GU tumors, particularly UC and RCC? Tell us a little bit about the complexity or perhaps the challenges you still see. At the same time, tell us about the successes. Dr. Rana McKay: Stepping back, let's just talk about like the principles and design of ADCs. So, most ADCs have three components. There's a monoclonal antibody that typically targets a cell surface antigen, which is conjugated by a linker, which is the second component, to a payload drug. And typically, that payload drug has been chemotherapy, whether it be topoisomerase or whether it be MMAE or other chemotherapeutic. We can start in the RCC space. There's been multiple antibody-drug conjugates that have been tested. There's antibody-drug conjugates to CD70, which is expressed on clear cell RCC. There's been antibody-drug conjugates to ENPP3, which is also expressed on RCC. There's antibody-drug conjugates to CDH6. And they have different payloads, like I said, whether it be topoisomerase I or other microtubule inhibitors. Now, when we think about kidney cancer, we don't treat this disease with chemotherapy. This disease is treated with immunotherapy. It is treated with treatments that target the VEGF pathway and historically has not been sensitive to chemo. So, I think even though the targets have been very exciting, we've seen very underwhelming data regarding activity, and in some context, seen increased toxicity with the ADCs. So, I think we need to tread lightly in the context of the integration and the testing of ADCs in RCC. We just came back from the KCRS meeting, and there was some very intriguing data about a c-Kit ADC that's being developed for chromophobe RCC, which is, you know, a huge unmet need, these variant tumors that really lack appropriate therapeutics. But I just caution us to tread lightly around how can we optimize the payload to make sure that the tumor that we're treating is actually sensitive to the agent that's targeting the cell kill. So, that's a little bit on the ADCs in RCC. I still think we have a long way to go and still in early testing. Now, ADCs for UC are now the standard of care. I think the prototypical agent, enfortumab vedotin, is a nectin-4-directed ADC that's conjugated to an MMAE payload and was the first ADC approved for advanced urothelial, received accelerated approval following the EV-201 trial, which was basically a multicenter, single-arm study that was investigating EV in cisplatin-ineligible patients with advanced urothelial carcinoma, and then ultimately confirmed in the EV-301 study as well. And so, that study ended up demonstrating the support superiority of EV from an overall survival standpoint, even PFS standpoint. Building on that backbone is the EV-302 study, which tested EV in combination with pembrolizumab versus platinum-based chemotherapy in the frontline setting. And that was a pivotal, landmark study that, like I said, has displaced platinum therapy as a frontline treatment for people with advanced urothelial carcinoma. And when we think about that study and the median overall survival and just how far we've come in urothelial cancer, the median OS with EV-pembro from that trial was 31 and a half months. I mean, that's just incredible. The control arm survival was 16 and a half months. The hazard ratio for OS, 0.47. I mean this is why when this data was presented, it was literally a standing ovation that lasted for several minutes because we just haven't seen data that have looked that good. And there are other antibody-drug conjugates that are being tested. We've all been involved in the saga with sacituzumab govitecan, which is a trophoblast cell surface antigen 2 (Trop-2) targeted ADC with a topoisomerase I payload. It was the second ADC to receive approval, but then that approval was subsequently withdrawn when the confirmatory phase 3 was negative, the TROPiCS-04 trial. So, approval was granted based off of the TROPHY-U-01, single-arm, phase 2 study, demonstrating a response rate of around 28% and a PFS of, you know, about 5 and a half months. But then failure to show any benefit from an OS standpoint. And I think there's a lot of controversy in the field around whether this agent still has a role in advanced urothelial carcinoma. And I think particularly for individuals who do not have molecular targets, like they're not HER2-amplified or have HER2-positivity or FGFR or other things like that. Dr. Pedro Barata: Fantastic summary, Rana. You were talking about the EV, and it came to mind that it might not be over, right, for the number of ADCs we use in clinical practice in the near future. I mean, we've seen very promising data for ADC against the HER2, right, and over-expression. It also can create some challenges, right, in the clinics because we're asking to test for HER2 expression. It's almost like, it's not exactly the same to do it in breast cancer, but it looks one more time that we're a little bit behind the breast cancer field in a lot of angles. And also has vedotin as a payload. Of course, I'm referring to disitamab vedotin, and there's very elegant data described by you in your review chapter as well. And it's going to be very interesting to see how we sequence the different ADCs, to your point as well. So, before we wrap it up, I just want to give you the opportunity to tell us if there's any area that we have not touched, any take-home points you'd like to bring up for our listeners before we call it a day. Dr. Rana McKay: Thank you so much. I have to say, you know, I was so excited at ASCO this year looking at the GU program. It was fantastic to see the progress being made, novel therapeutics that really there's a tremendous excitement about, not just in RCC and in UC, but also in prostate cancer, thinking about the integration of therapies, not just for people with refractory disease that, even though our goal is to improve survival, our likelihood of cure is low, but also thinking about how do we integrate these therapies early in the treatment landscape to enhance cure rates for patients, which is just really spectacular. We're seeing many of these agents move into the perioperative setting or in combination with radiation for localized disease. And then the special symposium on biomarkers, I mean, we've really come a long, long way. And I think that we're going to continue to evolve over the next several years. I'm super excited about where the field is going in the treatment of genitourinary malignancies. Dr. Pedro Barata: Oh, absolutely true. And I would say within the Annual Meeting, we have outstanding Educational Sessions. And just a reminder to the listeners that actually that's where the different teams or topics for the Educational Book chapters come from, from actually the educational sessions from ASCO. And your fantastic chapter is an example of that, right, focusing on advanced GU tumors. So, thank you so much, Rana, for taking the time, sharing your insights with us today on the podcast. It was a fantastic conversation as always. Dr. Rana McKay: My pleasure. Thanks so much for having me, Dr. Barata. Dr. Pedro Barata: Of course.  And thank you to our listeners for your time today. You will find the link to the article discussed today in the transcript of this episode. I also encourage you to check out the 2025 ASCO Educational Book. You'll find an incredible wealth of information there. It's free, available online, and you'll find, hopefully, super, super important information on the key science and issues that are shaping modern oncology, as we've heard from Dr. McKay and many other outstanding authors. So, thank you, everyone, and I hope to see you soon. 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. Pedro Barata @PBarataMD Dr. Rana McKay @DrRanaMcKay Follow ASCO on social media:        @ASCO on X (formerly Twitter)        ASCO on Bluesky       ASCO on Facebook        ASCO on LinkedIn        Disclosures:     Dr. Pedro Barata: Stock and Other Ownership Interests: Luminate Medical Honoraria: UroToday Consulting or Advisory Role: Bayer, BMS, Pfizer, EMD Serono, Eisai, Caris Life Sciences, AstraZeneca, Exelixis, AVEO, Merck, Ipson, Astellas Medivation, Novartis, Dendreon Speakers' Bureau: AstraZeneca, Merck, Caris Life Sciences, Bayer, Pfizer/Astellas Research Funding (Inst.): Exelixis, Blue Earth, AVEO, Pfizer, Merck  Dr. Rana McKay: Consulting or Advisory Role: Janssen, Novartis, Tempus, Pfizer, Astellas Medivation, Dendreon, Bayer, Sanofi, Vividion, Calithera, Caris Life Sciences, Sorrento Therapeutics, AVEO, Seattle Genetics, Telix, Eli Lilly, Blue Earth Diagnostics, Ambrx, Sumitomo Pharma Oncology, Esiai, NeoMorph, Arcus Biosciences, Daiichi Sankyo, Exelixis, Bristol Myers Squibb, Merck, Astrazeneca, Myovant Research Funding (Inst.): Bayer, Tempus, AstraZeneca, Exelixis, Bristol Myers Squibb, Oncternal Therapeutics, Artera    

Alzheimer's Disease Early Diagnosis and Management Evaluation and Credit:  https://www.surveymonkey.com/r/medchat82   Target Audience             This activity is targeted toward primary care physicians and advanced providers. Statement of Need A special report of Alzheimer's Disease Facts and Figures published in 2017, indicated 4 out of 5 Americans would want to know if they had Alzheimer's disease before it impacted their life. With the aging population the incidence of Alzheimer's is growing, according to the Alzheimer's Association over 7 million Americans are living with AD. This program will focus on screening and dx of AD in the early stages especially in pc offices, where patients will first present with cognitive symptoms. Additionally, this podcast will highlight the new blood biomarker test recently approved and its indications. Objectives  Differentiate between normal cognitive aging, mild cognitive impairment and early-stage Alzheimer's disease. Identify appropriate cognitive screening tools for use in primary care and their role in the early identification of Alzheimer's disease. Explain the mechanism and clinical relevance of blood-based biomarkers in the diagnosis of Alzheimer's disease, including the current guidelines and emerging practices. ModeratorRachel Hart, D.O. Geriatric Medicine Physician Memory and Cognitive Disorders Specialist Norton Neuroscience Institute Memory Center SpeakerGreg E. Cooper, M.D., Ph.D. Chief, Adult Neurology Medical Director, Memory Center Norton Neuroscience Institute   Planner Disclosure  The planners of this activity do not have any relevant financial relationships with ineligible companies to disclose. Moderator and Speaker DisclosureThe moderator, Gregory Cooper, M.D., Ph.D., discloses relevant financial relationships with Eli Lilly and Eisai (research). The speaker, Rachel Hart, D.O., discloses a relevant financial relationship with Eli Lilly (faculty).  All relevant financial relationships have been successfully mitigated. Commercial Support  There was no commercial support for this activity.  Physician CreditsAccreditation Norton Healthcare is accredited by the Kentucky Medical Association to provide continuing medical education for physicians. Designation Norton Healthcare designates this enduring material for a maximum of .50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Nursing Credits Norton Healthcare Institute for Education and Development is approved as a provider of nursing continuing professional development by the South Carolina Nurses Association, an accredited approver by the American Nurses Credentialing Center's Commission on Accreditation. This continuing professional development activity has been approved for 0.50 ANCC CE contact hours. In order for nursing participants to obtain credits, they must claim attendance by attesting to the number of hours in attendance.   For more information related to nursing credits, contact Sally Sturgeon, DNP, RN, SANE-A, AFN-BC at (502) 446-5889 or sally.sturgeon@nortonhealthcare.org.   Resources for Additional Study/ReferencesAmerican Perspectives on Early Detection of Alzheimer's Disease in the Era of Treatment https://www.alz.org/alzheimers-dementia/facts-figures   Blood Biomarkers to Detect Alzheimer Disease in Primary Care and Secondary Care https://pubmed.ncbi.nlm.nih.gov/39068545/   Date of Original Release | Sept. 2025; Information is current as of the time of recording.  Course Termination Date | Sept. 2028 Contact Information | Center for Continuing Medical Education; (502) 446-5955 or cme@nortonhealthcare.org Also listen to Norton Healthcare's podcast Stronger After Stroke. This podcast, produced by the Norton Neuroscience Institute, discusses difficult topics, answers frequently asked questions and provides survivor stories that provide hope. Norton Healthcare, a not for profit health care system, is a leader in serving adult and pediatric patients throughout Greater Louisville, Southern Indiana, the commonwealth of Kentucky and beyond. More information about Norton Healthcare is available at NortonHealthcare.com.

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma and Biotech world. Novo Nordisk's drug Wegovy has successfully reduced cardiovascular risk by 57% compared to tirzepatide. Eli Lilly has terminated two mid-stage trials for a second obesity asset, while Vertex Pharmaceuticals and Enlaza Therapeutics have formed a potential $2 billion partnership to develop drugs for autoimmune diseases. Biogen and Eisai have received FDA approval for the subcutaneous maintenance formulation of Leqvembi. Arrowhead Pharmaceuticals has secured a commitment of up to $2 billion from Novartis for an siRNA Parkinson's program. The FDA's new radiopharma guidance is expected to accelerate the space, and Teva has launched the first generic version of Novo Nordisk's obesity drug Saxenda. The pharmaceutical industry is navigating uncertainty during turbulent times, with companies focusing on innovation and new partnerships to drive progress.The FDA has issued new radiopharma guidance, which former FDA Commissioner Stephen Hahn believes is crucial for cancer therapy. Despite recent investments in radiopharmaceutical therapeutics by big pharma, the FDA's approval of updated COVID-19 vaccines with restrictions contradicts the medical freedom promised by health secretary Robert F. Kennedy Jr. Rare diseases secured four FDA firsts in August, including a win for Novo Nordisk's glp-1 drug WeGovy. Investment in new ALS therapies signals progress after setbacks, with new biotechs and collaborative initiatives showing promise at Bio2025. Other news includes the closure of Appia, Senate summons of Kennedy, updates on COVID-19 vaccines, and Lilly's obesity pill heading to the FDA. Thank you for listening to Pharma and Biotech daily.

In this episode of Wabi Sabi, I share the historical truth about matcha — from Eisai, the monk who first introduced powdered tea to Japan, to Sen no Rikyū, who refined the way of tea during the Tokugawa era. We trace matcha's roots through centuries of Japanese history, examining its role as a cultural and spiritual practice as well as a daily ritual. I also address the current shortage of ceremonial-grade matcha, why demand is outpacing supply, and what we can do about it. Finally, I call for better journalism around matcha — reporting that goes beyond trend-driven coverage to honor its sacred origins and the Japanese farmers and artisans who continue to protect and preserve this tradition. — Candice Kumai

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma and Biotech world.Vinay Prasad has returned to his position as director of the Center for Biologics Evaluation and Research at the FDA after a sudden exit less than two weeks ago. The FDA has restricted the patient pool for bluebird's Skysona gene therapy due to safety concerns, and Sarepta's AAV gene therapy platform has come under scrutiny following patient deaths from liver injuries. Genscript is celebrating a new era of innovation and trust.The text discusses the scrutiny faced by AAV gene therapy technology following patient deaths related to Sarepta Therapeutics' platform. There is a push for improvement in the technology, while some are looking to move on to other options. The article also highlights the importance of mRNA technology in cancer research and the need for continued investment in this area. Additionally, it mentions the FDA's decision on Biogen and Eisai's Alzheimer's drug, as well as five oral obesity drugs that could rival Lilly's Orforglipron. Other topics covered include cancer drug developments, gene therapy news, and upcoming industry events.Stay tuned for more updates on the latest news in the pharmaceutical and biotechnology industries.

Dr. Adam Kinnaird of the University of Alberta joins Dr. Aly-Khan Lalani and Dr. Christopher Wallis to explore the evolution of prostate cancer diagnostics, from the limitations of transrectal ultrasound to the rise of MRI and micro-ultrasound. They unpack key trials, discuss real-world challenges like long MRI wait times in Canada, and examine how micro-ultrasound offers a scalable, point-of-care solution. This can't-miss episode charts a path toward faster and more accurate prostate cancer care.This podcast has been made possible through unrestricted financial support by Novartis, Bayer, Astellas, Tolmar, Ipsen, J&J, Merck, Pfizer, Eisai and AbbVie.The View on GU with Lalani & Wallis integrates key clinical data from major conferences and high impact publications, sharing meaningful take home messages for practising clinicians in the field of genitourinary (GU) cancers. Learn more about The View on GU: theviewongu.ca

At ASCO 2025, Eisai presented data from its oncology portfolio, including in hepatocellular carcinoma and endometrial cancer. In a post-Congress conversation, web editor Nicole Raleigh spoke with Dr Corina Dutcus, senior vice president and oncology global clinical development lead at Eisai, who discussed the data and the company's continued commitment to innovation in the oncological field. Tune in to this and other ASCO 2025 conversations here. You can also listen to episode 196a of the pharmaphorum podcast in the player below, download the episode to your computer, or find it - and subscribe to the rest of the series – on Apple Podcasts, Spotify, Overcast, Pocket Casts, Podbean, and pretty much wherever else you download your other podcasts from.

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma and Biotech world. Biogen's sales of the partnered Alzheimer's drug Leqembi have climbed 20% in the second quarter, while CEO Chris Viehbacher dismisses rumors of disagreements with Eisai. Moderna has cut 10% of its global workforce as part of cost-cutting measures. AbbVie is celebrating the success of Skyrizi and Rinvoq, Lilly's Mounjaro shows promise in a cardiovascular trial, and there is optimism around Sarnas for therapeutic breakthroughs. Amidst industry challenges, many biopharma professionals are looking for new job opportunities.

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma e Biotech world.Vinay Prasad's departure from CBER has analysts anticipating a more traditional successor, while GSK streamlines its pipeline and pledges billions in US investments. Susan Monarez is now the confirmed CDC director, and the top biopharma venture capital raises of H1 2025 are summarized. Despite challenges like layoffs and market fluctuations, GSK remains committed to investing in the US despite tariffs. Other headlines include Madrigal's potential $2 billion investment, Biogen and Eisai's Alzheimer's drug update, and Novo Nordisk's new leadership. Trilink Biotechnologies is offering self-amplifying RNA constructs for potential therapeutic advancements.AI biotech companies have secured substantial funding in the first half of 2025, with continued investment pouring into startups within the industry. The top five biopharma venture capital raises of this period are highlighted. There is confusion surrounding Ira's definition of 'drug,' potentially hindering companies from pursuing approval for new formulations and indications. Vinay Prasad's departure from the FDA's Center for Biologics Evaluation and Research, following controversies related to Sarepta, has raised concerns among developers. Despite challenges, four biotech companies are successfully launching their products independently.Over 260 million people are impacted by rare diseases, emphasizing the need for faster evidence generation through global real-world data. GSK's commitment to investing in the US, Merck's cost-cutting measures to support its launch schedule, and Novo Nordisk's new leadership are also highlighted. The FDA has updated regulations regarding Sarepta's DMD gene therapy, making it available for ambulatory patients. Adaptimmune anticipates significant staff reductions following a cell therapy asset sale. Stay tuned for more updates on the latest developments in the biopharma industry.

The Sarepta saga continued into another week as the FDA recommended that the voluntary hold on the company's Duchenne muscular dystrophy gene therapy be lifted for ambulatory patients, after determining that the death of an 8-year-old Brazilian Duchenne patient who had received Elevidys' was not caused by the drug.  Sarepta's stock has swung wildly and its transparency questioned after it elected not to reveal the death of a third patient—a participant in a trial of a gene therapy for limb girdle muscular dystrophy—during a business update last week.    Speaking of entities—or individuals—who have trouble staying out of the news, Health Secretary Robert F. Kennedy Jr. plans to dissolve the U.S. Preventive Services Task Force because it is “too woke.” Also on Monday, Kennedy addressed what he called the “broken” vaccine injury compensation program. Without offering details, he vowed to “fix” the U.S.'s VICP and return it to its “original Congressional intent.”   On the business side of the biopharma house, Q2 earnings are in full swing, with AstraZeneca announcing estimate-beating numbers and CEO Pascal Soriot saying the world “needs to share” in global pharma R&D, while Merck cut $3 billion to support an aggressive launch schedule. Meanwhile, a week ahead of its own earnings report, Novo Nordisk named a new CEO and lowered its 2025 sales guidance for the second time this year.   In clinical development, the Alzheimer's Association Annual Conference is underway in Toronto, with Roche's trontinemab the standout so far. In a Phase Ib/IIa trial, the next-gen anti-amyloid antibody rapidly cleared amyloid from the brains of patients with Alzheimer's disease after just seven months—besting the 18-month timeframe for Biogen and Eisai's Leqembi and Eli Lilly's Kisunla. While Leqembi and Kisunla have shown some progress is slowing down the progression of Alzheimer's, their effect size is modest and they don't work for all patients—leaving plenty of room for symptomatic treatments, such as those being developed by Bristol Myers Squibb and Acadia Pharmaceuticals. The space is gearing up for several readouts, for both symptomatic and disease-modifying therapies alike.   And in BioPharm Executive this week, we dig into the top VC rounds so far this year and highlight a few scrappy biotechs walking the solo road.  

In der heutigen Folge sprechen die Finanzjournalisten Lea Oetjen und Holger Zschäpitz über einen Mega-Deal von Lucid, Billionen-Träume bei Netflix und den Absturz von Jungheinrich. Außerdem geht es um Quantumscape, Bigbear.AI, Aeva Technologies, D-Wave, Archer Aviation, Intuitive Machines, Rocket Lab, AST Spacemobile, Netflix, Disney, ComCast, Warner Brothers Discovery, Uber Technology, Interactive Brokers, TSMC, ASML, PepsiCo, Taiwan Semiconductor, Novartis, Richemont, ABB, Siemens, Salzgitter, Burberry, American Express, Tema Neuroscience and Mental Health ETF (WKN: A408EL), Vertex Pharmaceutical, Eisai, Biogen, Eli Lilly, DexCom, Siemens Healthineers, Johnson&Johnson, Pfizer, Lindbeck, GSK, Atai Life Science, Mind Medicine, iShares Core MSCI World (A0RPWH), Xtrackers MSCI World USD (A1XB5U), Vanguard FTSE All-World USD (A2PKXG), Xtrackers AI & Big Data (A2N6LC), Amundi MSCI World USD (ETF146), Amundi Core Stoxx Europe 600 (LYX0Q0), iShares MSCI ACWI (A1JMDF), Xtrackers II EUR Overnight (DBX0AN), WisdomTree Europe Defence ETF (A40Y9K), HanETF Future of Defence ETF (A3EB9T). Habt Ihr suizidale Gedanken, oder habt Ihr diese bei einem Angehörigen/Bekannten festgestellt? Hilfe bietet die Telefonseelsorge: Anonyme Beratung erhält man rund um die Uhr unter den kostenlosen Nummern 0800 / 111 0 111 und 0800 / 111 0 222. Auch eine Beratung über das Internet ist möglich unter http://www.telefonseelsorge.de. Eine Liste mit bundesweiten Hilfsstellen findet sich auf der Seite der Deutschen Gesellschaft für Suizidprävention. Wir freuen uns über Feedback an aaa@welt.de. Noch mehr "Alles auf Aktien" findet Ihr bei WELTplus und Apple Podcasts – inklusive aller Artikel der Hosts und AAA-Newsletter.[ Hier bei WELT.](https://www.welt.de/podcasts/alles-auf-aktien/plus247399208/Boersen-Podcast-AAA-Bonus-Folgen-Jede-Woche-noch-mehr-Antworten-auf-Eure-Boersen-Fragen.html.) [Hier] (https://open.spotify.com/playlist/6zxjyJpTMunyYCY6F7vHK1?si=8f6cTnkEQnmSrlMU8Vo6uQ) findest Du die Samstagsfolgen Klassiker-Playlist auf Spotify! Disclaimer: Die im Podcast besprochenen Aktien und Fonds stellen keine spezifischen Kauf- oder Anlage-Empfehlungen dar. Die Moderatoren und der Verlag haften nicht für etwaige Verluste, die aufgrund der Umsetzung der Gedanken oder Ideen entstehen. Hörtipps: Für alle, die noch mehr wissen wollen: Holger Zschäpitz können Sie jede Woche im Finanz- und Wirtschaftspodcast "Deffner&Zschäpitz" hören. +++ Werbung +++ Du möchtest mehr über unsere Werbepartner erfahren? [**Hier findest du alle Infos & Rabatte!**](https://linktr.ee/alles_auf_aktien) Impressum: https://www.welt.de/services/article7893735/Impressum.html Datenschutz: https://www.welt.de/services/article157550705/Datenschutzerklaerung-WELT-DIGITAL.html

Dr. Diwakar Davar and Dr. Jason Luke discuss novel agents in melanoma and other promising new data in the field of immunotherapy that were presented at the 2025 ASCO Annual Meeting. TRANSCRIPT Dr. Diwakar Davar: Hello. My name is Diwakar Davar, and I am welcoming you to the ASCO Daily News Podcast. I'm an associate professor of medicine and the clinical director of the Melanoma and Skin Cancer Program at the University of Pittsburgh's Hillman Cancer Center. Today, I'm joined by my colleague and good friend, Dr. Jason Luke. Dr. Luke is a professor of medicine. He is also the associate director of clinical research and the director of the Phase 1 IDDC Program at the University of Pittsburgh's Hillman Cancer Center. He and I are going to be discussing some key advancements in melanoma and skin cancers that were presented at the 2025 ASCO Annual Meeting. Our full disclosures are available in the transcript of this episode.  Jason, it is great to have you back on the podcast. Dr. Jason Luke: Thanks again so much for the opportunity, and I'm really looking forward to it. Dr. Diwakar Davar: Perfect. So we will go ahead and start talking a little bit about a couple of key abstracts in both the drug development immunotherapy space and the melanoma space. The first couple of abstracts, the first two, will cover melanoma. So, the first is LBA9500, which was essentially the primary results of RELATIVITY-098. RELATIVITY-098 was a phase 3 trial that compared nivolumab plus relatlimab in a fixed-dose combination against nivolumab alone for the adjuvant treatment of resected high-risk disease. Jason, do you want to maybe give us a brief context of what this is? Dr. Jason Luke: Yeah, it's great, thanks. So as almost all listeners, of course, will be aware, the use of anti–PD-1 immunotherapies really revolutionized melanoma oncology over the last 10 to 15 years. And it has become a standard of care in the adjuvant setting as well. But to review, in patients with stage III melanoma, treatment can be targeted towards BRAF with BRAF and MEK combination therapy, where that's relevant, or anti–PD-1 with nivolumab or pembrolizumab are a standard of care. And more recently, we've had the development of neoadjuvant approaches for palpable stage III disease. And in that space, if patients present, based on two different studies, either pembrolizumab or nivolumab plus ipilimumab can be given prior to surgery for somewhere in the 6- to 9-week range. And so all of these therapies have improved time-to-event endpoints, such as relapse-free or event-free survival. It's worth noting, however, that despite those advances, we've had a couple different trials now that have actually failed in this adjuvant setting, most high profile being the CheckMate-915 study, which looked at nivolumab plus ipilimumab and unfortunately was a negative study. So, with RELATIVITY-047, which was the trial of nivolumab plus relatlimab that showed an improvement in progression-free survival for metastatic disease, there's a lot of interest, and we've been awaiting these data for a long time for RELATIVITY-098, which, of course, is this adjuvant trial of LAG-3 blockade with relatlimab plus nivolumab. Dr. Diwakar Davar: Great. So with that, let's briefly discuss the trial design and the results. So this was a randomized, phase 3, blinded study, so double-blinded, so neither the investigators knew what the patients were getting, nor did the patients know what they were getting. The treatment investigational arm was nivolumab plus relatlimab in the fixed-dose combination. So that's the nivolumab standard fixed dose with relatlimab that was FDA approved in RELATIVITY-047. And the control arm was nivolumab by itself. The duration of treatment was 1 year. The patient population consisted of resected high-risk stage III or IV patients. The primary endpoint was investigator-assessed RFS. Stage and geography were the standard stratifying factors, and they were included, and most of the criteria were balanced across both arms. What we know at this point is that the 2-year RFS rate was 64% and 62% in the nivolumab and nivolumab-combination arms, respectively. The 2-year DMFS rate was similarly equivalent: 76% with nivolumab monotherapy, 73% with the combination. And similar to what you had talked about with CheckMate 915, unfortunately, the addition of LAG-3 did not appear to improve the RFS or DMFS compared to control in this patient population. So, tell us a little bit about your take on this and what do you think might be the reasons why this trial was negative? Dr. Jason Luke: It's really unfortunate that we have this negative phase 3 trial. There had been a lot of hope that the combination of nivolumab with relatlimab would be a better tolerated combination that increased the efficacy. So in the metastatic setting, we do have 047, the study that demonstrated nivolumab plus relatlimab, but now we have this negative trial in the adjuvant setting. And so as to why exactly, I think is a complicated scenario. You know, when we look at the hazard ratios for relapse-free survival, the primary endpoint, as well as the secondary endpoints for distant metastasis-free survival, we see that the hazard ratio is approximately 1. So there's basically no difference. And that really suggests that relatlimab in this setting had no impact whatsoever on therapeutic outcomes in terms of efficacy. Now, it's worth noting that there was a biomarker subanalysis that was presented in conjunction with these data that looked at some immunophenotyping, both from circulating T cells, CD8 T cells, as well as from the tumor microenvironment from patients who were treated, both in the previous metastatic trial, the RELATIVITY-047 study, and now in this adjuvant study in the RELATIVITY-098 study. And to briefly summarize those, what was identified was that T cells in advanced melanoma seemed to have higher expression levels of LAG-3 relative to T cells that are circulating in patients that are in the adjuvant setting. In addition to that, there was a suggestion that the magnitude of increase is greater in the advanced setting versus adjuvant. And the overall summary of this is that the suggested rationale for why this was a negative trial may have been that the target of LAG-3 is not expressed as highly in the adjuvant setting as it is in the metastatic setting. And so while the data that were presented, I think, support this kind of an idea, I am a little bit cautious that this is actually the reason for why the trial was negative, however. I would say we're not really sure yet as to why the trial was negative, but the fact that the hazard ratios for the major endpoints were essentially 1 suggests that there was no impact whatsoever from relatlimab. And this really makes one wonder whether or not building on anti–PD-1 in the adjuvant setting is feasible because anti–PD-1 works so well. You would think that even if the levels of LAG-3 expression were slightly different, you would have seen a trend in one direction or another by adding a second drug, relatlimab, in this scenario. So overall, I think it's an unfortunate circumstance that the trial is negative. Clearly there's going to be no role for relatlimab in the adjuvant setting. I think this really makes one wonder about the utility of LAG-3 blockade and how powerful it really can be. I think it's probably worth pointing out there's another adjuvant trial ongoing now of a different PD-1 and LAG-3 combination, and that's cemiplimab plus fianlimab, a LAG-3 antibody that's being dosed from another trial sponsor at a much higher dose, and perhaps that may make some level of difference. But certainly, these are unfortunate results that will not advance the field beyond where we were at already. Dr. Diwakar Davar: And to your point about third-generation checkpoint factors that were negative, I guess it's probably worth noting that a trial that you were involved with, KeyVibe-010, that evaluated the PD-1 TIGIT co-formulation of vibostolimab, MK-4280A, was also, unfortunately, similarly negative. So, to your point, it's not clear that all these third-generation receptors are necessarily going to have the same impact in the adjuvant setting, even if they, you know, for example, like TIGIT, and they sometimes may not even have an effect at all in the advanced cancer setting. So, we'll see what the HARMONY phase 3 trial, that's the Regeneron cemiplimab/fianlimab versus pembrolizumab control with cemiplimab with fianlimab at two different doses, we'll see how that reads out. But certainly, as you've said, LAG-3 does not, unfortunately, appear to have an impact in the adjuvant setting. So let's move on to LBA9501. This is the primary analysis of EORTC-2139-MG or the Columbus-AD trial. This was a randomized trial of encorafenib and binimetinib, which we will abbreviate as enco-bini going forward, compared to placebo in high-risk stage II setting in melanoma in patients with BRAF V600E or K mutant disease. So Jason, you know, you happen to know one or two things about the resected stage II setting, so maybe contextualize the stage II setting for us based on the trials that you've led, KEYNOTE-716, as well as CheckMate-76K, set us up to talk about Columbus-AD. Dr. Jason Luke: Thanks for that introduction, and certainly stage II disease has been something I've worked a lot on. The rationale for that has been that building off of the activity of anti–PD-1 in metastatic melanoma and then seeing the activity in stage III, like we just talked about, it was a curious circumstance that dating back about 7 to 8 years ago, there was no availability to use anti–PD-1 for high-risk stage II patients, even though the risk of recurrence and death from melanoma in the context of stage IIB and IIC melanoma is in fact similar or actually higher than in stage IIIA or IIIB, where anti–PD-1 was approved. And in that context, a couple of different trials that you alluded to, the Keynote-716 study that I led, as well as the CheckMate 76K trial, evaluated pembrolizumab and nivolumab, respectively, showing an improvement in relapse-free and distant metastasis-free survival, and both of those agents have subsequently been approved for use in the adjuvant setting by the US FDA as well as the European Medicines Agency.  So bringing then to this abstract, throughout melanoma oncology, we've seen that the impact of anti–PD-1 immunotherapy versus BRAF and MEK-targeted therapy have had very similar outcomes on a sort of comparison basis, both in frontline metastatic and then in adjuvant setting. So it was a totally reasonable question to ask: Could we use adjuvant BRAF and MEK inhibitor therapy? And I think all of us expected the answer would be yes. As we get into the discussion of the trial, I think the unfortunate circumstance was that the timing of this clinical trial being delayed somewhat, unfortunately, made it very difficult to accrue the trial, and so we're going to have to try to read through the tea leaves sort of, based on only a partially complete data set. Dr. Diwakar Davar: So, in terms of the results, they wanted to enroll 815 patients, they only enrolled 110. The RFS and DMFS were marginally improved in the treatment arm but certainly not significantly, which is not surprising because the trial had only accrued 16% to 18% of its complete accrual. As such, we really can't abstract from the stage III COMBI-AD data to stage II patients. And certainly in this setting, one would argue that the primary treatment options certainly remain either anti–PD-1 monotherapy, either with pembrolizumab or nivolumab, based on 716 or 76K, or potentially active surveillance for the patients who are not inclined to get treated.  Can you tell us a little bit about how you foresee drug development going forward in this space because, you know, for example, with HARMONY, certainly IIC disease is a part of HARMONY. We will know at least a little bit about that in this space. So what do you think about the stage IIB/C patient population? Is this a patient population in which future combinations are going to be helpful, and how would you think about where we can go forward from here? Dr. Jason Luke: It is an unfortunate circumstance that this trial could not be accrued at the pace that was necessary. I think all of us believe that the results would have been positive if they'd been able to accrue the trial. In the preliminary data set that they did disclose of that 110 patients, you know, it's clear there is a difference at a, you know, a landmark at a year. They showed a 16% difference, and that would be in line with what has been seen in stage III. And so, you know, I think it's really kind of too bad. There's really going to be no regulatory approach for this consideration. So using BRAF and MEK inhibition in stage II is not going to be part of standard practice moving into the future. To your point, though, about where will the field go? I think what we're already realizing is that in the adjuvant setting, we're really overtreating the total population. And so beyond merely staging by AJCC criteria, we need to move to biomarker selection to help inform which patients truly need the treatment. And in that regard, I don't think we've crystallized together as a field as yet, but the kinds of things that people are thinking about are the integration of molecular biomarkers like ctDNA. When it's positive, it can be very helpful, but in melanoma, we found that, unfortunately, the rates are quite low, you know, in the 10% to 15% range in the adjuvant setting. So then another consideration would be factors in the primary tumor, such as gene expression profiling or other considerations.  And so I think the future of adjuvant clinical trials will be an integration of both the standard AJCC staging system as well as some kind of overlaid molecular biomarker that helps to enrich for a higher-risk population of patients because on a high level, when you abstract out, it's just clearly the case that we're rather substantially overtreating the totality of the population, especially given that in all of our adjuvant studies to date for anti–PD-1, we have not yet shown that there's an overall survival advantage. And so some are even arguing perhaps we should even reserve treatment until patients progress. I think that's a complicated subject, and standard of care at this point is to offer adjuvant therapy, but certainly a lot more to do because many patients, you know, unfortunately, still do progress and move on to metastatic disease. Dr. Diwakar Davar: Let's transition to Abstract 2508. So we're moving on from the melanoma to the novel immunotherapy abstracts. And this is a very, very, very fascinating drug. It's IMA203. So Abstract 2508 is a phase 1 clinical update of IMA203. IMA203 is an autologous TCR-T construct targeting PRAME in patients with heavily pretreated PD-1-refractory metastatic melanoma. So Jason, in the PD-1 and CTLA-4-refractory settings, treatment options are either autologous TIL, response rate, you know, ballpark 29% to 31%, oncolytic viral therapy, RP1 with nivolumab, ORR about 30-ish percent. So new options are needed. Can you tell us a little bit about IMA203? Perhaps tell us for the audience, what is the difference between a TCR-T and traditional autologous TIL? And a little bit about this drug, IMA203, and how it distinguishes itself from the competing TIL products in the landscape. Dr. Jason Luke: I'm extremely enthusiastic about IMA203. I think that it really has transformative potential based on these results and hopefully from the phase 3 trial that's open to accrual now. So, what is IMA203? We said it's a TCR-T cell product. So what that means is that T cells are removed from a patient, and then they can be transduced through various technologies, but inserted into those T cells, we can then add a T-cell receptor that's very specific to a single antigen, and in this case, it's PRAME. So that then is contrasted quite a bit from the TIL process, which includes a surgical resection of a tumor where T cells are removed, but they're not specific necessarily to the cancer, and they're grown up in the lab and then given to the patient. They're both adoptive cell transfer products, but they're very different. One is genetically modified, and the other one is not. And so the process for generating a TCR-T cell is that patients are required to have a new biomarker that some may not be familiar with, which is HLA profiling. So the T-cell receptor requires matching to the concomitant HLA for which the peptide is bound in. And so the classic one that is used in most oncology practices is A*02:01 because approximately 48% of Caucasians have A*02:01, and the frequency of HLA in other ethnicities starts to become highly variable. But in patients who are identified to have A*02:01 genotype, we can then remove blood via leukapheresis or an apheresis product, and then insert via lentiviral transduction this T-cell receptor targeting PRAME. Patients are then brought back to the hospital where they can receive lymphodepleting chemotherapy and then receive the reinfusion of the TCR-T cells. Again, in contrast with the TIL process, however, these T cells are extremely potent, and we do not need to give high-dose interleukin-2, which is administered in the context of TIL. Given that process, we have this clinical trial in front of us now, and at ASCO, the update was from the phase 1 study, which was looking at IMA203 in an efficacy population of melanoma patients who were refractory at checkpoint blockade and actually multiple lines of therapy. So here, there were 33 patients and a response rate of approximately 50% was observed in this population of patients, notably with a duration of response approximately a year in that treatment group. And I realize that these were heavily pretreated patients who had a range of very high-risk features. And approximately half the population had uveal melanoma, which people may be aware is a generally speaking more difficult-to-treat subtype of melanoma that metastasizes to the liver, which again has been a site of resistance to cancer immunotherapy. So these results are extremely promising. To summarize them from what I said, it's easier to make TCR-T cells because we can remove blood from the patient to transduce the T cells, and we don't have to put them through surgery. We can then infuse them, and based on these results, it looks like the response rate to IMA203 is a little bit more than double what we expect from lifileucel. And then, whereas with lifileucel or TILs, we have to give high-dose IL-2, here we do not have to give high-dose IL-2. And so that's pretty promising. And a clinical trial is ongoing now called the SUPREME phase 3 clinical trial, which is hoping to validate these results in a randomized global study. Dr. Diwakar Davar: Now, one thing that I wanted to go over with you, because you know this trial particularly well, is what you think of the likelihood of success, and then we'll talk a little bit about the trial design. But in your mind, do you think that this is a trial that has got a reasonable likelihood of success, maybe even a high likelihood of success? And maybe let's contextualize that to say an alternative trial, such as, for example, the TebeAM trial, which is essentially a T-cell bispecific targeting GP100. It's being compared against SOC, investigator's choice control, also in a similarly heavily pretreated patient population. Dr. Jason Luke: So both trials, I think, have a strong chance of success. They are very different kinds of agents. And so the CD3 bispecific that you referred to, tebentafusp, likely has an effect of delaying progression, which in patients with advanced disease could have a value that might manifest as overall survival. With TCR-T cells, by contrast, we see a very high response rate with some of the patients going into very durable long-term benefit. And so I do think that the SUPREME clinical trial has a very high chance of success. It will be the first clinical trial in solid tumor oncology randomizing patients to receive a cell therapy as compared with a standard of care. And within that standard of care control arm, TILs are allowed as a treatment. And so it will also be the first study that will compare TCR-T cells against TILs in a randomized phase 3. But going back to the data that we've seen in the phase 1 trial, what we observe is that the duration of response is really connected to the quality of the response, meaning if you have more than a 50% tumor shrinkage, those patients do very, very well. But even in patients who have less than 50% tumor shrinkage, the median progression-free survival right now is about 4.5 months. And again, as we think about trial design, standard of care options for patients who are in this situation are unfortunately very bad. And the progression-free survival in that population is probably more like 2 months. So this is a trial that has a very high likelihood of being positive because the possibility of long-term response is there, but even for patients who don't get a durable response, they're likely going to benefit more than they would have based on standard chemotherapy or retreatment with an anti–PD-1 agent. Dr. Diwakar Davar: Really, a very important trial to enroll, a trial that is first in many ways. First of a new generation of TCR-T agents, first trial to look at cell therapy in the control arm, a new standard of efficacy, but potentially also if this trial is successful, it will also be a new standard of trial conduct, a new kind of trial, of a set of trials that will be done in the second-line immunotherapy-refractory space. So let's pivot to the last trial that we were going to discuss, which was Abstract 2501. Abstract 2501 is a first-in-human phase 1/2 trial evaluating BNT142, which is the first-in-class mRNA-encoded bispecific targeting Claudin-6 and CD3 in patients with Claudin-positive tumors. We'll talk a little bit about this, but maybe let's start by talking a little bit about Claudin-6. So Claudin-6 is a very interesting new target. It's a target that's highly expressed in GI and ovarian tumors. There are a whole plethora of Claudin-6-targeting agents, including T-cell bispecifics and Claudin-6-directed CAR-Ts that are being developed. But BNT142 is novel. It's a novel lipid nanoparticle LNP-encapsulated mRNA. The mRNA encodes an anti–Claudin-6 CD3 bispecific termed RiboMAB-021. And it then is administered to the patient. The BNT142-encoding mRNA LNPs are taken up by the liver and translated into the active drug. So Jason, tell us a little bit about this agent. Why you think it's novel, if you think it's novel, and let's talk a little bit then about the results. Dr. Jason Luke: So I certainly think this is a novel agent, and I think this is just the first of what will probably become a new paradigm in oncology drug development. And so you alluded to this, but just to rehash it quickly, the drug is encoded as genetic information that's placed in the lipid nanoparticle and then is infused into the patient. And after the lipid nanoparticles are taken up by the liver, which is the most common place that LNPs are usually taken up, that genetic material in the mRNA starts to be translated into the actual protein, and that protein is the drug. So this is in vivo generation, so the patient is making their own drug inside their body. I think it's a really, really interesting approach. So for any drug that could be encoded as a genetic sequence, and in this case, it's a bispecific, as you mentioned, CD3-Claudin-6 engager, this could have a tremendous impact on how we think about pharmacology and novel drug development moving into the future in oncology. So I think it's an extremely interesting drug, the like of which we'll probably see only more moving forward. Dr. Diwakar Davar: Let's maybe briefly talk about the results. You know, the patient population was heavily pretreated, 65 or so patients, mostly ovarian cancer. Two-thirds of the patients were ovarian cancer, the rest were germ cell and lung cancer patients. But let's talk a little bit about the efficacy. The disease control rate was about 58% in the phase 1 population as a whole, but 75% in the ovarian patient population. Now tell us a little bit about the interesting things about the drug in terms of the pharmacokinetics, and also then maybe we can pivot to the clinical activity by dose level. Dr. Jason Luke: Well, so they did present in their presentation at ASCO a proportionality showing that as higher doses were administered, that greater amounts of the drug were being made inside the patient. And so that's an interesting observation, and it's an important one, right? Suggesting that the pharmacology that we classically think of by administering drugs by IV, for example, would still be in play. And that did translate into some level of efficacy, particularly at the higher dose levels. Now, the caveat that I'll make a note of is that disease control rate is an endpoint that I think we have to be careful about because what that really means is sometimes a little bit unclear. Sometimes patients have slowly growing tumors and so on and so forth. And the clinical relevance of disease control, if it doesn't last at least 6 months, I think is probably pretty questionable. So I think these are extremely interesting data, and there's some preliminary sense that getting the dose up is going to matter because the treatment responses were mostly observed at the highest dose levels. There's also a caveat, however, that across the field of CD3 bispecific molecules like this, there's been quite a bit of heterogeneity in terms of the response rate, with some of them only really generating stable disease responses and other ones having more robust responses. And so I think this is a really interesting initial foray into this space. My best understanding is this molecule is not moving forward further after this, but I think that this really does set it up to be able to chase after multiple different drug targets on a CD3 bispecific backbone, both in ovarian cancer, but then basically across all of oncology. Dr. Diwakar Davar: Perfect. This is a very new sort of exciting arena where we're going to be looking at, in many ways, these programmable constructs, whether we're looking at in vivo-generated, in this case, a T-cell bispecific, but we've also got newer drugs where we are essentially giving drugs where people are generating in vivo CAR T, and also potentially even in vivo TCR-T. But certainly lots of new excitement around this entire class of drugs. And so, what we'd like to do at this point in time is switch to essentially the fact that we've got a very, very exciting set of data at ASCO 2025. You've heard from Dr. Luke regarding the advances in both early drug development but also in advanced cutaneous melanoma. And Jason, as always, thank you so much for sharing your very valuable and great, fantastic insights with us on the ASCO Daily News Podcast. Dr. Jason Luke: Well, thanks again for the opportunity. Dr. Diwakar Davar: And thank you to our listeners for taking your time to listen today. You will find the links to the abstracts that we discussed today in the transcript of this episode. And finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers:    Dr. Diwakar Davar    @diwakardavar    Dr. Jason Luke @jasonlukemd Follow ASCO on social media:     @ASCO on Twitter       ASCO on Bluesky   ASCO on Facebook       ASCO on LinkedIn   Disclosures:     Dr. Diwakar Davar:      Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences     Consulting or Advisory Role: Instil Bio, Vedanta Biosciences     Consulting or Advisory Role (Immediate family member): Shionogi     Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences     Research Funding (Inst.): Zucero Therapeutics     Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy     Dr. Jason Luke:     Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX     Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine     Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure     Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof)     Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio

Dr. Neeraj Agarwal and Dr. Jeanny Aragon-Ching discuss important advances in the treatment of prostate, bladder, and kidney cancers that were presented at the 2025 ASCO Annual Meeting. TRANSCRIPT Dr. Neeraj Agarwal: Hello, and welcome to the ASCO Daily News Podcast. I am Dr. Neeraj Agarwal, your guest host of the ASCO Daily News Podcast today. I am the director of the Genitourinary Oncology Program and a professor of medicine at the University of Utah Huntsman Cancer Institute and editor-in-chief of the ASCO Daily News.  I am delighted to be joined by Dr. Jeanny Aragon-Ching, a GU medical oncologist and the clinical program director of the GU Center at the Inova Schar Cancer Institute in Virginia. Today, we will be discussing some key abstracts in GU oncology that were presented at the 2025 ASCO Annual Meeting.  Our full disclosures are available in the transcript of this episode.  Jeanny, it is great to have you on the podcast. Dr. Jeanny Aragon-Ching: Oh, thank you so much, Neeraj. Dr. Neeraj Agarwal: Jeanny, let's begin with some prostate cancer abstracts. Let's begin with Abstract 5017 titled, “Phase 1 study results of JNJ-78278343 (pasritamig) in metastatic castration-resistant prostate cancer.” Can you walk us through the design and the key findings of this first-in-human trial? Dr. Jeanny Aragon-Ching: Yeah, absolutely, Neeraj. So this study, presented by Dr. Capucine Baldini, introduces pasritamig, a first-in-class T-cell redirecting bispecific antibody that simultaneously binds KLK2 on prostate cancer cells and CD3 receptor complexes on T cells. KLK2 is also known as human kallikrein 2, which is selectively expressed in prostate tissue. And for reference, KLK3 is what we now know as the PSA, prostate-specific antigen, therefore making it an attractive and specific target for therapeutic engagement. Now, while this was an early, first-in-human, phase 1 study, it enrolled 174 heavily pretreated metastatic CRPC patients. So many were previously treated with ARPIs, taxanes, and radioligand therapy. So given the phase 1 nature of this study, the primary objective was to determine the safety and the RP2D, which is the recommended phase 2 dose. Secondary objectives included preliminary assessment of antitumor activity. So, pasritamig was generally well tolerated. There were no treatment-related deaths. Serious adverse events were rare. And in the RP2D safety cohort, where patients received the step-up dosing up to 300 mg of IV every 6 weeks, the most common treatment-related adverse events were low-grade infusion reactions. There was fatigue and grade 1 cytokine release syndrome, what we call CRS. And no cases of neurotoxicity, or what we call ICANS, the immune effector cell-associated neurotoxicity syndrome, reported. Importantly, the CRS occurred in just about 8.9% of patients. All were grade 1. No patients required tocilizumab or discontinued treatment due to adverse events. So, this suggests a favorable safety profile, allowing hopefully for outpatient administration without hospitalization, which will be very important when we're thinking about bispecifics moving forward. In terms of efficacy, pasritamig showed promising activity. About 42.4% of evaluable patients achieved a PSA50 response. Radiographic PFS was about 6.8 months. And among patients with measurable disease, the objective response rate was about 16.1% in those with lymph node or bone metastases, and about 3.7% in those with visceral disease, with a median duration of response of about 11.3 months. So, altogether, this data suggests that pasritamig may offer a well-tolerated and active new potential option for patients with metastatic CRPC.   Again, as a reminder, with the caveat that this is still an early phase 1 study. Dr. Neeraj Agarwal: Thank you, Jeanny. These are promising results for a bispecific T-cell engager, pasritamig, in prostate cancer. I agree, the safety and durability observed here stand out, and this opens the door for further development, possibly even in earlier disease settings.  So, shifting now from immunotherapy to the evolving role of genomics in prostate cancer. So let's discuss Abstract 5094, a real-world, retrospective analysis exploring the prognostic impact of homologous recombination repair gene mutations, especially BRCA1 and BRCA2 mutations, in metastatic hormone-sensitive prostate cancer. Can you tell us more about this abstract, Jeanny? Dr. Jeanny Aragon-Ching: Sure, Neeraj. So this study was presented by Dr. David Olmos, represents one of the largest real-world analyses we have evaluating the impact of homologous recombination repair, or what we would call HRR, alterations in metastatic hormone-sensitive prostate cancer. So, this cohort included 556 men who underwent paired germline and somatic testing. Now, about 30% of patients had HRR alterations, with about 12% harboring BRCA1 or BRCA2 mutations and 16% having alterations in other HRR genes. Importantly, patients were stratified via CHAARTED disease volume, and outcomes were examined across treatment approaches, including ADT alone, doublet therapy, and triplet therapy. The prevalence of BRCA and HRR alterations were about similar between the metastatic hormone-sensitive prostate cancer and the metastatic castrate-resistant prostate cancer, with no differences observed, actually, between the patients with high volume versus low volume disease.  So, the key finding was that BRCA and HRR alterations were associated with poor clinical outcomes in metastatic hormone-sensitive prostate cancer. And notably, the impact of these alterations may actually be even greater in metastatic hormone-sensitive prostate cancer than previously reported in metastatic CRPC. So, the data showed that when BRCA mutations are present, the impact of the volume of disease is actually limited. So, poor outcomes were observed across the board for both high-volume and low-volume groups. So, the analysis showed that patients with HRR alterations had significantly worse outcomes compared to patients without HRR alterations. Median radiographic progression-free survival was about 20.5 months for the HRR-altered patients versus 30.6 months for the non-HRR patients, with a hazard ratio of 1.6. Median overall survival was 39 months for HRR-altered patients compared to 55.7 months for the non-HRR patients, with a hazard ratio of 1.5. Similar significant differences were observed when BRCA-mutant patients were compared with patients harboring non-BRCA HRR mutations. Overall, poor outcomes were independent of treatment of ARPI or taxanes. Dr. Neeraj Agarwal: Thank you, Jeanny. So, these data reinforce homologous recombination repair mutations as both a predictive and prognostic biomarker, not only in the mCRPC, but also in the metastatic hormone-sensitive setting as well. It also makes a strong case for incorporating genomic testing early in the disease course and not waiting until our patients have castration-resistant disease. Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. And I think this really brings home the point and the lead up to the AMPLITUDE trial, which is LBA5006, a phase 3 trial that builds on this very concept of testing with a PARP inhibitor, niraparib, in the hormone-sensitive space. Can you tell us a little bit more about this abstract, Neeraj? Dr. Neeraj Agarwal: Sure. So, the AMPLITUDE trial, a phase 3 trial presented by Dr. Gerhardt Attard, enrolled 696 patients with metastatic hormone-sensitive prostate cancer and HRR gene alterations. 56% of these patients had BRCA1 and BRCA2 mutations. Patients were randomized to receive abiraterone with or without niraparib, a PARP inhibitor. The majority of patients, 78% of these patients, had high-volume metastatic hormone-sensitive prostate cancer, and 87% of these patients had de novo metastatic HSPC. And 16% of these patients received prior docetaxel, which was allowed in the clinical trial. So, with a median follow-up of nearly 31 months, radiographic progression-free survival was significantly prolonged with the niraparib plus abiraterone combination, and median was not reached in this arm, compared to abiraterone alone, which was 29.5 months, with a hazard ratio of 0.63, translating to a 37% reduction in risk of progression or death. This benefit was even more pronounced in the BRCA1 and BRCA2 subgroup, with a 48% reduction in risk of progression, with a hazard ratio of 0.52. Time to symptomatic progression also improved significantly across all patients, including patients with BRCA1, BRCA2, and HRR mutations. Although overall survival data remain immature, early trends favored the niraparib plus abiraterone combination. The safety profile was consistent with prior PARP inhibitor studies, with grade 3 or higher anemia and hypertension were more common but manageable. Treatment discontinuation due to adverse events remained low at 11%, suggesting that timely dose modifications when our patients experience grade 3 side effects may allow our patients to continue treatment without discontinuation. These findings support niraparib plus abiraterone as a potential new standard of care in our patients with metastatic hormone-sensitive prostate cancer with HRR alterations, and especially in those who had BRCA1 and BRCA2 mutations. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. This trial is especially exciting because it brings PARP inhibitors earlier into the treatment paradigm. Dr. Neeraj Agarwal: Exactly. And it is exciting to see the effect of PARP inhibitors in the earlier setting.  So Jeanny, now let's switch gears a bit to bladder cancer, which also saw several impactful studies. Could you tell us about Abstract 4502, an exploratory analysis from the EV-302 trial, which led to approval of enfortumab vedotin plus pembrolizumab for our patients with newly diagnosed metastatic bladder cancer? So here, the authors looked at the outcomes in patients who achieved a confirmed complete response with EV plus pembrolizumab. Dr. Jeanny Aragon-Ching: Sure, Neeraj. So, EV-302 demonstrated significant improvements in progression-free and overall survival for patients previously treated locally advanced or metastatic urothelial cancer, I'll just call it metastatic UC, as a frontline strategy, establishing EV, which is enfortumab vedotin, plus pembro, with pembrolizumab as standard of care in this setting.  So, this year at ASCO, Dr Shilpa Gupta presented this exploratory responder analysis from the phase 3 EV-302 trial. Among 886 randomized patients, about 30.4% of patients, this is about 133, in the EV+P arm, and 14.5% of the patients in the chemotherapy arm, achieved a confirmed complete response. They call it the CCR rates. So for patients who achieved this, median PFS was not reached with EV+P compared to 26.9 months with chemotherapy, with a hazard ratio of 0.36, translating to a 64% reduction in the risk of progression. Overall survival was also improved. So the median OS was not reached in either arm, but the hazard ratio favored the EV+P at 0.37, translating to a 63% reduction in the risk of death. The median duration of complete response was not reached with EV+P compared to 15.2 months with chemotherapy. And among those patients who had confirmed CRs at 24 months, 78% of patients with the EV+P arm remained progression-free, and around 95% of the patients were alive, compared to 54% of patients who were progression-free and 86% alive of the patients in the chemotherapy arm. Safety among responders were also consistent with prior reports. Grade 3 or higher treatment-related adverse events occurred in 62% of EV+P responders and 72% of chemotherapy responders. Most adverse events were managed with dose modifications, and importantly, no treatment-related deaths were reported among those who were able to achieve complete response.  So these findings further reinforce EV and pembro as the preferred first-line therapy for metastatic urothelial carcinoma, offering a higher likelihood of deep, durable responses with a fairly manageable safety profile. Dr. Neeraj Agarwal: Thank you for the great summary, Jeanny. These findings underscore the depth and durability of responses achievable with this combination and also suggest that achieving a response may be a surrogate for long-term benefit in patients with metastatic urothelial carcinoma.  So now, let's move to Abstract 4503, an exploratory ctDNA analysis from the NIAGARA trial, which evaluated perioperative durvalumab, an immune checkpoint inhibitor, in muscle-invasive bladder cancer. So what can you tell us about this abstract? Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. So, in NIAGARA, presented by Dr. Tom Powles, the addition of perioperative durvalumab to neoadjuvant chemotherapy, gem/cis, significantly improved event-free survival, overall survival, and pathologic complete response in patients with cisplatin-eligible muscle-invasive bladder cancer. Recall that this led to the U.S. FDA approval of this treatment regimen on March 28, 2025.  So, a planned exploratory analysis evaluated the ctDNA dynamics and their association with clinical outcomes, which was the one presented recently at ASCO. So, the study found that the incidence of finding ctDNA positivity in these patients was about 57%. Following neoadjuvant treatment, this dropped to about 22%, with ctDNA clearance being more common in the durvalumab arm, about 41%, compared to the chemotherapy control arm of 31%. Notably, 97% of patients who remained ctDNA positive prior to surgery failed to achieve a pathologic CR. So, this indicates a strong association between ctDNA persistence and lack of tumor eradication. So, postoperatively, only about 9% of patients were ctDNA positive. So, importantly, durvalumab conferred an event-free survival benefit regardless of ctDNA status at both baseline and post-surgery. Among patients who were ctDNA positive at baseline, durvalumab led to a hazard ratio of 0.73 for EFS. So, this translates to a 27% reduction in the risk of disease recurrence, progression, or death compared to the control arm. In the post-surgical ctDNA-positive group, the disease-free survival was also improved with a hazard ratio of 0.49, translating to a 51% reduction in the risk of recurrence.  So, these findings underscore the prognostic value of ctDNA and suggest that durvalumab provides clinical benefit irrespective of molecular residual disease status. So, the data also supports that ctDNA is a promising biomarker for future personalized strategies in the perioperative treatment of muscle-invasive bladder cancer. Dr. Neeraj Agarwal: Thank you, Jeanny. It is great to see that durvalumab is improving outcomes in these patients regardless of ctDNA status. However, based on these data, presence of ctDNA in our patients warrants a closer follow-up with imaging studies, because these patients with positive ctDNA seem to have a higher risk of recurrence. Dr. Jeanny Aragon-Ching: I agree, Neeraj.  Let's round out the bladder cancer discussion with Abstract 4518, which reported the interim results of SURE-02, which is a phase 2 study evaluating neoadjuvant sacituzumab govitecan plus pembrolizumab in cisplatin-ineligible muscle-invasive bladder cancer. Can you tell us more about this abstract, Neeraj? Dr. Neeraj Agarwal: Sure, Jeanny. So, Dr Andrea Necchi presented interim results from the SURE-02 trial. This is a phase 2 study evaluating neoadjuvant sacituzumab govitecan plus pembrolizumab, followed by a response-adapted bladder-sparing treatment and adjuvant pembrolizumab in patients with muscle-invasive bladder cancer.  So, in this interim analysis, 40 patients were treated and 31 patients were evaluable for efficacy. So, the clinical complete response rate was 38.7%. All patients achieving clinical complete response underwent bladder-sparing approach with a repeat TURBT instead of radical cystectomy. Additionally, 51.6% of patients achieved excellent pathologic response with a T stage of 1 or less after neoadjuvant therapy. The treatment was well tolerated, with only 12.9% of patients experiencing grade 3 or higher adverse events without needing dose reduction of sacituzumab. Molecular profiling, interestingly, showed that clinical complete response correlated with luminal and genomically unstable subtypes, while high stromal gene expression was associated with lack of response.  These results suggest that sacituzumab plus pembrolizumab combination has promising activity in this setting, and tolerability, and along with other factors may potentially allow a bladder preservation approach in a substantial number of patients down the line. Dr. Jeanny Aragon-Ching: Yeah, agree with you, Neeraj. And the findings are very provocative and support completing the full trial enrollment and further exploration of this strategy in muscle-invasive bladder cancer in order to improve and provide further bladder-sparing strategies. Dr. Neeraj Agarwal: Agree. So, let's now turn to the kidney cancer, starting with Abstract 4505, the final overall analysis from CheckMate-214 trial, which evaluated nivolumab plus ipilimumab, so dual checkpoint inhibition strategy, versus sunitinib in our patients with metastatic clear cell renal cell carcinoma. Dr. Jeanny Aragon-Ching: Yeah, absolutely, Neeraj. So, the final 9-year analysis of the phase 3 CheckMate-214 trial confirms the long-term superiority of nivolumab and ipilimumab over sunitinib for first-line treatment of advanced metastatic renal cell carcinoma. So, this has a median follow-up of 9 years. Overall survival remains significantly improved with the combination. So, in the ITT patient population, the intention-to-treat, the hazard ratio for overall survival was 0.71. So, this translates to a 29% reduction in the risk of death. 31% of patients were alive at this 108-month follow-up compared to 20% only in those who got sunitinib. So, similar benefits were observed in the intermediate- and poor-risk groups with a hazard ratio of 0.69, and 30% versus 19% survival at 108 months.  Importantly, a delayed benefit was also seen in those favorable-risk patients. So, the hazard ratio for overall survival improved from 1.45 in the initial report and now at 0.8 at 9 years follow-up, with 35% of patients alive at 108 months compared to 22% in those who got sunitinib. Progression-free survival also favored the nivo-ipi arm across all risk groups. At 96 months, the probability of remaining progression-free was about 23% compared to 9% in the sunitinib arm in the ITT patient population, 25% versus 9% in the intermediate- and poor-risk patients, and 13% compared to 11% in the favorable-risk patients. Importantly, at 96 months, 48% of patients in the nivo-ipi responders remained in response compared to just 19% in those who got sunitinib. And in the favorable-risk group, 36% of patients who responded remained in response, although data were not available for sunitinib in this subgroup.  So, this data reinforces the use of nivolumab and ipilimumab as a durable and effective first-line effective strategy for standard of care across all risk groups for advanced renal cell carcinoma. Dr. Neeraj Agarwal: Thank you, Jeanny. And of course, since ipi-nivo data were presented, several other novel ICI-TKI combinations have emerged. And I'm really hoping to see very similar data with TKI-ICI combinations down the line. It is really important to note that we are not seeing any new safety signals with the ICI combinations or ICI-based therapies, which is very reassuring given the extended exposure. Dr. Jeanny Aragon-Ching: Absolutely agree with you there, Neeraj.  Now, going on and moving on to Abstract 4514, which is the KEYNOTE-564 trial, and they reported on the 5-year outcomes of adjuvant pembrolizumab in clear cell RCC in patients who are at high risk for recurrence. Can you tell us a little bit more about this abstract, Neeraj? Dr. Neeraj Agarwal: Sure. So, the KEYNOTE-564 trial established pembrolizumab monotherapy as the first adjuvant regimen to significantly improve both disease-free survival and overall survival compared to placebo after surgery for patients with clear cell renal cell carcinoma. So, Dr Naomi Haas presented the 5-year update from this landmark trial.  A total of 994 patients were randomized to receive either pembrolizumab or placebo. The median follow-up at the time of this analysis was approximately 70 months. Disease-free survival remained significantly improved with pembrolizumab. The median DFS was not reached with pembrolizumab compared to 68.3 months with placebo, with a hazard ratio of 0.71, translating to a 29% reduction in risk of recurrence. At 5 years, 60.9% of patients receiving pembrolizumab remained disease-free compared to 52.2% with placebo. Overall survival also favored pembrolizumab. The hazard ratio for OS was 0.66, translating to a 34% reduction in risk of death, with an estimated 5-year overall survival rate of 87.7% with pembrolizumab compared to 82.3% for placebo. Importantly, these benefits were consistent across all key subgroups, including patients with sarcomatoid features. In addition, no new serious treatment-related adverse events have been reported in the 3 years since treatment completion.  So, these long-term data confirm pembrolizumab as a durable and effective standard adjuvant therapy for patients with resected, high-risk clear cell renal cell carcinoma. Dr. Jeanny Aragon-Ching: Thank you for that wonderful summary, Neeraj. Dr. Neeraj Agarwal: That wraps up our kidney cancer highlights. Any closing thoughts, Jeanny, before we conclude? Dr. Jeanny Aragon-Ching: It's been so wonderful reviewing these abstracts with you, Neeraj. So, the 2025 ASCO Annual Meeting showcased a lot of transformative data across GU cancers, from first-in-class bispecifics to long-term survival in RCC. And these findings are already shaping our clinical practices. Dr. Neeraj Agarwal: I agree. And we have covered a broad spectrum of innovations in GU cancers with strong clinical relevance.  So, thank you, Jeanny, for joining me today and sharing your insights.  And thank you to our listeners for joining us. You will find links to the abstracts discussed today in the transcript of this episode. If you find these conversations valuable, please take a moment to rate, review, and subscribe to the ASCO Daily News Podcast wherever you listen. Thank you so much. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers:    Dr. Neeraj Agarwal     @neerajaiims     Dr. Jeanny Aragon-Ching   Follow ASCO on social media:       @ASCO on Twitter       ASCO on Bluesky   ASCO on Facebook       ASCO on LinkedIn       Disclosures:   Dr. Neeraj Agarwal:   Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences  Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas  Dr. Jeanny Aragon-Ching:   Honoraria: Bristol-Myers Squibb, EMD Serono, Astellas Scientific and Medical Affairs Inc., Pfizer/EMD Serono   Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant, Exelixis,    Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb, Astellas/Seattle Genetics

Dr. Vamsi Velcheti and Dr. Nate Pennell discuss novel treatment approaches in small cell and non-small cell lung cancer that were featured at the 2025 ASCO Annual Meeting. TRANSCRIPT Dr. Vamsi Velcheti: Hello, I'm Dr. Vamsi Velcheti, your guest host of the ASCO Daily News Podcast. I'm a professor of medicine and chief of hematology and oncology at the Mayo Clinic in Jacksonville, Florida. The 2025 ASCO Annual Meeting featured some exciting advancements in small cell lung cancer, targeted therapies for non-small cell lung cancer, and other novel [treatment] approaches. Today, I'm delighted to be joined by Dr. Nate Pennell to discuss some of the key abstracts that are advancing the lung cancer field. Dr. Pennell is the co-director of the Cleveland Clinic Lung Cancer Program and also the vice chair of clinical research at the Taussig Cancer Institute. Our full disclosures are available in the transcript of this episode. Nate, it's great to have you back on the podcast. Thanks so much for being here. Dr. Nate Pennell: Thanks, Vamsi. Always a pleasure. Dr. Vamsi Velcheti: Let's get started, and I think the first abstract that really caught my attention was Abstract 8516, “The Randomized Trial of Relevance of Time of Day of Immunotherapy for Progression-Free and Overall Survival in Patients With Non-Small Cell Lung Cancer.” What are your thoughts about this, Nate? Dr. Nate Pennell: I agree. I thought this was one of the most discussed abstracts, certainly in the lung cancer session, but I think even outside of lung cancer, it got some discussion. So, just to put this in perspective, there have been a number of publications that have all been remarkably consistent, and not just in lung cancer but across multiple cancer types, that immunotherapy, immune checkpoint inhibitors, are commonly used. And all of them have suggested, when looking at retrospective cohorts, that patients who receive immune checkpoint inhibitors earlier in the day – so in the morning or before the early afternoon – for whatever reason, appear to have better outcomes than those who get it later in the day, and this has been repeated. And I think many people just sort of assumed that this was some sort of strange association and that there was something fundamentally different from a prognostic standpoint in people who came in in the morning to get their treatment versus those who came later in the afternoon, and that was probably the explanation. The authors of this randomized trial actually decided to test this concept. And so, about 210 patients with previously untreated advanced non-small cell lung cancer were randomly assigned to get chemo and immune checkpoint inhibitor – either pembrolizumab or sintilimab – and half of them were randomly assigned to get the treatment before 3 PM in the afternoon, and half of them were assigned to get it after 3 PM in the afternoon. And it almost completely recapitulated what was seen in the retrospective cohorts. So, the median progression-free survival in those who got earlier treatment was 13.2 months versus only 6.5 months in those who got it later in the day. So, really enormous difference with a hazard ratio of 0.43, which was statistically significant. And perhaps even more striking, the median overall survival was not reached in the early group versus 17.8 months in the late group with a hazard ratio of 0.43, also highly statistically significant. Even the response rate was 20% higher in the early patients; 75% response rate compared to 56% in the late-time-of-day patients. So very consistent across all measures of efficacy with pretty good matched characteristics across the different groups. And so, I have to tell you, I don't know what to make of this. I certainly was a skeptic about the retrospective series, but now we have a prospective randomized trial that shows essentially the same thing. So, maybe there is a difference between getting treated in the morning, although I have yet to hear someone give a very good mechanistic explanation as to why this would be. What were your thoughts on this? Dr. Vamsi Velcheti: It's indeed fascinating, Nate, and I actually think this was a very interesting abstract. Really, I was caught off guard looking at the data. I mean, if it were a drug, we would be so excited, right? I mean, with those kind of survival benefits. I don't know. I think circadian rhythm probably has something to do with it, like different cytokine profiles at the time of administration. I mean, who knows? But I think it's a randomized trial, and I think I would expect to see a mad rush for treatment appointments early in the morning given this, and at least I want my patients to come in first thing in the morning. It'll be interesting to see. Dr. Nate Pennell: It's important to point out that in this study, everyone got chemo and immunotherapy. And, at least in our cancer center, most patients who are getting platinum-doublet chemotherapy and immunotherapy actually do get treated earlier in the day already, just because of the length of the infusion appointment that's needed. So it really is oftentimes people getting single-agent immunotherapy who are often getting the later, shorter visits. But if you have a choice, I think it would be very reasonable to have people treated earlier in the day. And I do think most of the impressions that I got from people about this is that they would like to see it reproduced but certainly well worth further investigation. And I personally would like to see more investigation into what the rationale would be for this because I still can't quite figure out, yes, if you got it at, say, you know, 5 PM, that's later in the day and I can understand that maybe your immune system is somewhat less receptive at that point than it would be in the morning. But because these checkpoint inhibitors have such long half-lives, it's still in your system the next morning when your immune system is supposedly more receptive. So I don't quite understand why that would be the case. Well, let's move on to the next study. I would like to hear your thoughts on Abstract 8515, “Plasma-Guided, Adaptive First-Line Chemoimmunotherapy for Non-Small Cell Lung Cancer.” Dr. Vamsi Velcheti: Yeah, this was another abstract that seems to be really interesting in my opinion. I think there's kind of a lot of emphasis lately on ctDNA and MRD-based assays to monitor disease. In the lung cancer space, we haven't had a lot of clinical trials looking at this prospectively, and this was one of those pilot studies where they looked at circulating free DNA (cfDNA)-based response-adaptive strategy for frontline patients who are PD-L1 positive. So, patients started with pembrolizumab monotherapy, and based on plasma molecular response after 2 cycles, those patients without response received early treatment intensification with a platinum doublet. So the approach essentially was to reduce the chemotherapy exposure in patients who respond to immunotherapy. And only about 17.5% of the patients on the trial received chemotherapy based on lack of molecular response. So, in this trial, what they found was patients with the cfDNA response had a markedly improved PFS of 16.4 months versus 4.8 months. So essentially, like, this is a really nice study to set a foundation on which we have to do larger studies to incorporate molecular markers trying to look at cfDNA response to inform treatment strategy, either escalation or de-escalation strategies. So, I thought it was a very interesting study. Dr. Nate Pennell: Yeah. I mean, we always have this question for patients, “Should they get immunotherapy alone or combined with chemo?” and I think this certainly is intriguing, suggesting that there may be ways you can monitor people and perhaps rescue those that aren't going to respond to single agent. I'd like to see a randomized trial against, you know, this strategy, perhaps against everyone getting, say, chemoimmunotherapy or make sure that you're not potentially harming people by doing this strategy. But I agree, it's time to move beyond just observing that cell-free DNA is prognostic and important and start using it to actually guide treatment. Dr. Vamsi Velcheti: Yeah, and I would just caution though, like, you know, I think we need more data, but, however, it's certainly a very interesting piece of data to kind of help inform future trials. So, there was another abstract that caught my attention, and I think this would be a very interesting abstract in the EGFR space. Abstract 8506, "Patritumab Deruxtecan (HER3-DXd) in Resistant EGFR-Mutant Advanced Non-Small Cell Lung Cancer Patients After Third-Generation EGFR TKI," it's the HERTHENA-Lung02 study. What do you think about the results of this study? Dr. Nate Pennell: Yeah, this was, I would say, very widely anticipated and ultimately a little disappointing, despite being a positive trial. So, these are patients with EGFR-mutant non-small cell lung cancer who have progressed after a third-generation EGFR TKI like osimertinib. This is really an area of major unmet need. We do have drugs like amivantamab in this space, but still definitely an area where essentially patients move from having a highly effective oral therapy to being in the realm of chemotherapy as their best option. So, this HER3 antibody-drug conjugate, patritumab deruxtecan, had some good single-arm data for this. And we're sort of hoping this would become an available option for patients. This trial was designed against platinum-doublet chemotherapy in this setting and with a primary endpoint of progression-free survival. And it actually was positive for improved progression-free survival compared to chemo with a hazard ratio of 0.77. But when you look at the medians, you can see that the median PFS was only 5.8 versus 5.4 months. It was really a modest difference between the two arms. And on the interim analysis, it appeared that there will not be a difference in overall survival between the two arms. In fact, the hazard ratio at the interim analysis was 0.98 for the two arms. So based on this, unfortunately, the company that developed the HER3-DXd has withdrawn their application to the FDA for approval of the drug, anticipating that they probably wouldn't get past approval without that overall survival endpoint. So, unfortunately, probably not, at least for the near future, going to be a new option for these patients. Dr. Vamsi Velcheti: Yeah, I think this is a space that's clearly an unmet need, and this was a big disappointment, I should say. I think all of us were going into the meeting anticipating some change in the standard of care here. Dr. Nate Pennell: Yeah, I agree. It was something that I was telling patients, honestly, that I was expecting this to be coming, and so now, definitely a bit of a disappointment. But it happens and, hopefully, it will still find perhaps a role or other drugs with a similar target. Certainly an active area. Well, let's leave the EGFR-mutant space and move into small cell. There were a couple of very impactful studies. And one of them was Abstract 8006, “Lurbinectedin Plus Atezolizumab as First-Line Maintenance Treatment in Patients With Extensive-Stage Small Cell Lung Cancer, Primary Results from the Phase III IMforte Trial.” So, what was your impression of this? Dr. Vamsi Velcheti: Yeah, I think this is definitely an interesting study, and small cell, I remember those days when we had barely any studies of small cell at ASCO, and now we have a lot of exciting developments in the small cell space. It's really good to see. The IMforte trial is essentially like a maintenance lurbinectedin trial with atezolizumab maintenance. And the study was a positive trial. The primary endpoint was a PFS, and the study showed improvement in both PFS and OS with the addition of lurbinectedin to atezolizumab maintenance. And definitely, it's a positive trial, met its primary endpoint, but I always am a little skeptical of adding maintenance cytotoxic therapies here in this setting. In my practice, and I'd like to hear your opinion, Nate, most patients with small cell after 4 cycles of a platinum doublet, they're kind of really beaten up. Adding more cytotoxic therapy in the maintenance space is going to be tough, I think, for a lot of patients. But also, most importantly, I think this rapidly evolving landscape for patients with small cell lung cancer with multiple new, exciting agents, actually like some FDA-approved like tarlatamab, also like a lot of these emerging therapeutics like I-DXd and other ADCs in this space. You kind of wonder, is it really optimal strategy to bring on like another cytotoxic agent right after induction chemotherapy, or do you kind of delay that? Or maybe have like a different strategy in terms of maintenance. I know that the tarlatamab maintenance trial is probably going to read out at some point too. I think it's a little challenging. The hazard ratio is also 0.73. As I said, it's a positive trial, but it's just incremental benefit of adding lurbi. And also on the trial, we need to also pay attention to the post-progression second-line treatments, number of patients who received tarlatamab or any other investigational agents.  So I think it's a lot of questions still. I'm not quite sure I'd be able to embrace this completely. I think a vast majority of my patients might not be eligible anyway for cytotoxic chemotherapy maintenance right away, but yeah, it's tough. Dr. Nate Pennell: Yeah. I would call this a single and not a home run. It definitely is real. It was a real overall survival benefit. Certainly not surprising that a maintenance therapy would improve progression-free survival. We've known that for a long time in small cell, but first to really show an overall survival benefit. But I completely agree with you. I mean, many people are not going to want to continue further cytotoxics after 4 cycles of platinum-doublet chemo. So I would say, for those that are young and healthy and fly through chemo without a lot of toxicity, I think certainly something worth mentioning. The problem with small cell, of course, is that so many people get sick so quickly while on that observation period after first-line chemo that they don't make it to second-line treatment. And so, giving everyone maintenance therapy essentially ensures everyone gets that second-line treatment. But they also lose that potentially precious few months where they feel good and normal and are able to be off of treatment. So, I would say this is something where we're really going to have to kind of sit and have that shared decision-making visit with patients and decide what's meaningful to them. Dr. Vamsi Velcheti: Yeah, I agree. The next abstract that was a Late-Breaking Abstract, 8000, “Overall Survival of Neoadjuvant Nivolumab Plus Chemotherapy in Patients With Resectable Non-Small Cell Lung Cancer in CheckMate-816.” This was a highly anticipated read-out of the OS data from 816. What did you make of this abstract? Dr. Nate Pennell: Yeah, I thought this was great. Of course, CheckMate-816 changed practice a number of years ago when it first reported out. So, this was the first of the neoadjuvant or perioperative chemoimmunotherapy studies in resectable non-small cell lung cancer. So, just to review, this was a phase 3 study for patients with what we would now consider stage II or stage IIIA resectable non-small cell lung cancer. And they received three cycles of either chemotherapy or chemotherapy plus nivolumab, and that was it. That was the whole treatment. No adjuvant treatment was given afterwards. They went to resection. And patients who received the chemoimmunotherapy had a much higher pathologic complete response rate and a much better event-free survival. And based on this, this regimen was approved and, I think, at least in the United States, widely adopted.  Now, since the first presentation of CheckMate 816, there have been a number of perioperative studies that have included an adjuvant component of immunotherapy – KEYNOTE-671, the AEGEAN study – and these also have shown improved outcomes. The KEYNOTE study with pembrolizumab also with an overall survival benefit. And I think people forgot a little bit about CheckMate-816. So, this was the 5-year overall survival final analysis. And it did show a statistically and, I think, clinically meaningful difference in overall survival with the 3 cycles of neoadjuvant chemo-nivo compared to chemo with a hazard ratio of 0.72. The 5-year overall survival of 65% in the chemo-IO group versus 55% with the chemo alone. So a meaningful improvement. And interestingly, that hazard ratio of 0.72 is very similar to what was seen in the peri-operative pembro study that included the adjuvant component. So, very much still relevant for people who think that perhaps the value of those neoadjuvant treatments might be really where most of the impact comes from this type of approach. They also gave us an update on those with pathologic complete response, showing really astronomically good outcomes. If you have a pathologic complete response, which was more than a quarter of patients, the long-term survival was just phenomenal. I mean, 95% alive at 5 years if they were in that group and suggesting that in those patients at least, the adjuvant treatment may not be all that important.  So, I think this was an exciting update and still leaves very much the open question about the importance of continuing immunotherapy after surgery after the neoadjuvant component. Dr. Vamsi Velcheti: Yeah, I completely agree, Nate. I think the million-dollar question is: “Is there like a population of patients who don't have complete response but like maybe close to complete response?” So, would you like still consider stopping adjuvant IO? I probably would not be comfortable, but I think sometimes, you know, we all have patients who are like very apprehensive of continuing treatments. So, I think that we really need more studies, especially for those patients who don't achieve a complete CR. I think trying to find strategies for like de-escalation based on MRD or other risk factors. But we need more trials in that space to inform not just de-escalation, but there are some patients who don't respond at all to a neoadjuvant IO. So, there may be an opportunity for escalating adjuvant therapies. So, it is an interesting space to watch out for. Dr. Nate Pennell: No, absolutely. Moving to KRAS-mutant space, so our very common situation in patients with non-small cell lung cancer, we had the results of Abstract 8500, “First-Line Adagrasib With Pembrolizumab in Patients With Advanced or Metastatic KRASG12C-Mutated Non-Small Cell Lung Cancer” from the phase 2 portion of the KRYSTAL-7 study. Why was this an interesting and important study? Dr. Vamsi Velcheti: First of all, there were attempts to kind of combine KRASG12C inhibitors in the past with immune checkpoint inhibitors, notably sotorasib with pembrolizumab. Unfortunately, those trials have led to like a lot of toxicity, with increased especially liver toxicity, which was a major issue. This is a phase 2 study of adagrasib in combination with pembrolizumab, and this is a study in the frontline setting in patients with the G12C-mutant metastatic non-small cell lung cancer. And across all the PD-L1 groups, the ORR was 44%, and the median PFS was 11 months, comparable to the previous data that we have seen with adagrasib in this setting. So it's not like a major improvement in clinical efficacy. However, I think the toxicity profile that we were seeing was slightly better than the previous trials in combination with sotorasib, but you still have a fair amount of transaminitis even in the study. At this point, this is not ready for clinical primetime. I don't think we should be using sotorasib or adagrasib in the frontline or even in the second line in combination with checkpoint inhibitors. Combining these drugs with checkpoint inhibitors in the clinical practice might lead to adverse outcomes. So, we need to wait for more data like newer-generation G12C inhibitors which are also being studied in combination, so we'll have to kind of wait for more data to emerge in this space. Dr. Nate Pennell: I agree, this is not immediately practice changing. This is really an attempt to try to combine targeted treatment with immune checkpoint inhibitor. And I agree with you that, you know, it does appear to be perhaps a little bit better tolerated than some of the prior combinations that have tried in this space. The outcomes overall were not that impressive, although in the PD-L1 greater than 50%, it did have a better response rate perhaps than you would expect with either drug alone. And I do think that the company is focusing on that population for a future randomized trial, which certainly would inform this question better. But in the meantime, I agree with you, there's a lot of newer drugs that are coming along that potentially may be more active and better tolerated. And so, I'd say for now, interesting but we'll wait and see. Dr. Vamsi Velcheti: Yeah, so now moving back again to small cell. So, there was a Late-Breaking Abstract, 8008. This is a study of tarlatamab versus chemotherapy as second-line treatment for small cell lung cancer. They presented the primary analysis of the phase III DeLLphi-304 study. What do you think about this? Dr. Nate Pennell: Yeah, I thought this was really exciting. This was, I would say, perhaps the most important lung study that was presented. Tarlatamab is, of course, the anti-DLL3 bispecific T-cell engager compound, which is already FDA approved based on a prior single-arm phase II study, which showed a very nice response rate as a single agent in previously treated small cell lung cancer and relatively manageable side effects, although somewhat unique to solid tumor docs in the use of these bispecific drugs in things like cytokine release syndrome and ICANS, the neurologic toxicities. So, this trial was important because tarlatamab was approved, but there were also other chemotherapy drugs approved in the previously treated space. And so, this was a head-to-head second-line competition comparison between tarlatamab and either topotecan, lurbinectedin, or amrubicin in previously treated small cell patients with a primary endpoint of overall survival. So, a very well-designed trial. And it did show, I think, a very impressive improvement in overall survival with a median overall survival in the tarlatamab group of 13.6 months compared to 8.3 months with chemotherapy, hazard ratio of 0.6. And progression-free survival was also longer at 4.2 months versus 3.2 months, hazard ratio of 0.72. In addition to showing improvements in cancer-related symptoms that were improved in tarlatamab compared to chemotherapy, there was actually also significantly lower rates of serious treatment-related adverse events with tarlatamab compared to chemotherapy. So, you do still see the cytokine release syndrome, which is seen in most people but is manageable because these patients are admitted to the hospital for the first two cycles, as well as a significant number of patients with neurologic side effects, the so-called ICANS, which also can be treated with steroids. And so, I think based upon the very significant improvement in outcomes, I would expect that this should become our kind of standard second-line treatment since it seems to be much better than chemo. However, tarlatamab is definitely a new drug that a lot of places are not used to using, and I think a lot of cancer centers, especially ones that aren't tied to a hospital, may have questions about how to deal with the CRS. So, I'm curious your thoughts on that. Dr. Vamsi Velcheti: Yeah, thank you, Nate. And I completely agree. I think the data looked really promising, and I've already been using tarlatamab in the second-line space. The durability of response and overall, having used tarlatamab quite a bit - like, I participated in some of the early trials and also used it as standard of care - tarlatamab has unique challenges in terms of like need for hospitalization for monitoring for the first few treatments and make sure, you know, we monitor those patients for CRS and ICANS. But once you get past that initial administration and monitoring of CRS, these patients have a much better quality of life, they're off chemotherapy, and I think it's really about the logistics of actually administering tarlatamab and coordination with the hospital and administration in the outpatient setting. It's definitely challenging, but I think it definitely can be done and should be done given what we are seeing in terms of clinical efficacy here. Dr. Nate Pennell: I agree. I think hospital systems now are just going to have to find a way to be able to get this on formulary and use it because it clearly seems to be more effective and generally better tolerated by patients. So, should move forward, I think. Finally, there's an abstract I wanted to ask you about, Abstract 8001, which is the “Neoadjuvant osimertinib with or without chemotherapy versus chemotherapy alone in resectable epidermal growth factor receptor-mutated non-small cell lung cancer: The NeoADAURA Study”. And this is one that I think was also fairly highly anticipated. So, what are your thoughts? Dr. Vamsi Velcheti: You know, I wasn't probably surprised with the results, and I believe we were all expecting a positive trial, and we certainly were handed a positive trial here. It's a phase III trial of osimertinib and chemotherapy or osimertinib in the neoadjuvant space followed by surgery, followed by osimertinib. It's a global phase 3 trial and very well conducted, and patients with stage II to stage IIIB were enrolled in the study. And in the trial, patients who had a neoadjuvant osimertinib with or without chemotherapy showed a significant improvement in major pathologic response rates over chemotherapy alone. And the EFS was also positive for osimertinib and chemotherapy, osimertinib monotherapy as well compared to chemotherapy alone. So overall, the study met its primary endpoint, and I think it sheds light on how we manage our patients with early-stage lung cancer. I think osimertinib, we know that osimertinib is already FDA approved in the adjuvant space, but what we didn't really know is how was osimertinib going to work in the neoadjuvant space. And there are always situations, especially for stage III patients, where we are on the fence about, are these patients already close to being metastatic? They have, like, almost all these patients have micrometastatic disease, even if they have stage III. As we saw in the LAURA data, when you look at the control arm, it was like a very short PFS. Chemoradiation does nothing for those patients, and I think these patients have systemic mets, either gross or micrometastatic disease at onset. So, it's really important to incorporate osimertinib early in the treatment course. And I think, especially for the locally advanced patients, I think it's even more important to kind of incorporate osimertinib in the neoadjuvant space and get effective local control with surgery and treat them with adjuvant. I'm curious to hear your thoughts, Nate. Dr. Nate Pennell: I am a believer and have long been a believer in targeted adjuvant treatments, and, you know, it has always bothered me somewhat that we're using our far and away most effective systemic therapy; we wait until after they go through all their pre-op treatments, they go through surgery, then they go through chemotherapy, and then finally months later, they get their osimertinib, and it still clearly improves survival in the adjuvant setting. Why not just start the osimertinib as soon as you know that the patient has EGFR-mutant non-small cell lung cancer, and then you can move on to surgery and adjuvant treatment afterwards? And I think what was remarkable about this study is that all of these patients almost - 90% in each arm - went to surgery. So, you weren't harming them with the neoadjuvant treatment. And clearly better major pathologic response, nodal downstaging, event-free survival was better. But I don't know that this trial is ever going to show an overall survival difference between neoadjuvant versus just surgery and adjuvant treatment, given how effective the drug is in the adjuvant setting. Nonetheless, I think the data is compelling enough to consider this, certainly for our N2-positive, stage IIIA patients or a IIIB who might be otherwise surgical candidates. I think based on this, I would certainly consider that. Dr. Vamsi Velcheti: Yeah, and especially for EGFR, like even for stage IIIB patients, in the light of the LAURA study, those patients who do not do too well with chemoradiation. So you're kind of delaying effective systemic therapy, as you said, waiting for the chemoradiation to finish. So I think probably time to revisit how we kind of manage these locally advanced EGFR patients. Dr. Nate Pennell: Yep, I agree. Dr. Vamsi Velcheti: Nate, thank you so much for sharing your fantastic insights today on the ASCO Daily News Podcast. It's been an exciting ASCO again. You know, we've seen a lot of positive trials impacting our care of non-small cell lung cancer and small cell lung cancer patients. Dr. Nate Pennell: Thanks for inviting me, Vamsi. Always a pleasure to discuss these with you. Dr. Vamsi Velcheti: And thanks to our listeners for your time today. You will find links to all of the abstracts discussed today in the transcript of the episode. Finally, if you value the insights that you hear from the ASCO Daily News Podcast, please take a moment to rate, review, subscribe wherever you get your podcast. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. More on today's speakers:    Dr. Vamsi Velcheti   @VamsiVelcheti    Dr. Nathan Pennell   @n8pennell   Follow ASCO on social media:     @ASCO on Twitter     ASCO on Facebook     ASCO on LinkedIn   ASCO on BlueSky   Disclosures:   Dr. Vamsi Velcheti:   Honoraria: ITeos Therapeutics   Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen, Elevation Oncology, Taiho Oncology, Merus   Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline   Dr. Nathan Pennell:     Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron    Research Funding (Inst): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi 

Dr. John Sweetenham and Dr. Erika Hamilton highlight key abstracts that were presented at ASCO25, including advances in breast and pancreatic cancers as well as remarkable data from the use of structured exercise programs in cancer care. Transcript Dr. Sweetenham: Hello, and welcome to the ASCO Daily News Podcast. I'm your host, Dr. John Sweetenham. Today, we'll be discussing some of the key advances and novel approaches in cancer care that were presented at the 2025 ASCO Annual Meeting. I'm delighted to be joined again by the chair of the Meeting's Scientific Program, Dr. Erika Hamilton. She is a medical oncologist and director of breast cancer and gynecologic cancer research at the Sarah Cannon Research Institute in Nashville, Tennessee.  Our full disclosures are available in the transcript of this episode. Dr. Hamilton, congratulations on a fantastic meeting. From the practice-changing science to the world-renowned speakers at this year's Meeting, ASCO25 really reflected the amazing progress we're seeing in oncology today and the enormous opportunities that lie ahead of us. And thanks for coming back on to the podcast today to discuss some of these advances. Dr. Hamilton: Thanks, Dr. Sweetenham. I'm happy to join you today. It really was an impactful ASCO Annual Meeting. I probably am biased, but some great research was presented this year, and I heard lots of great conversations happening while we were there. Dr. Sweetenham: Yeah, absolutely. There was a lot of buzz, as well as a lot of media buzz around the meeting this year, and I think that's probably a good place to start. So I'd like to dive into abstract number LBA3510. This was the CHALLENGE trial, which created a lot of buzz at the meeting and subsequently in the media. This is the study that was led by the NCI Canada Clinical Trials Group, which was the first randomized phase 3 trial in patients with stage III and high-risk stage II colon cancer, which demonstrated that a post-treatment structured exercise program is both feasible and effective in improving disease-free survival in this patient group. The study was performed over a long period of time and in many respects is quite remarkable. So, I wonder if you could give us your thoughts about this study and whether you think that this means that our futures are going to be full of structured exercise programs for those patients who may benefit. Dr. Hamilton: It's a fantastic question. I think that this abstract did create a lot of buzz. We were very excited when we read it. It was highlighted in one of the Clinical Science Symposium sessions. But briefly, this was a phase 3 randomized trial. It was conducted at 55 centers, so really a broad experience, and patients that had resected colon cancer who completed adjuvant therapy were allowed to participate. There were essentially 2 groups: a structured exercise program, called ‘the exercise group,' or health education materials alone, so that was called just ‘the health education group.' And this was a 3-year intervention, so very high quality. The primary end point, as you mentioned, was disease-free survival. This actually accrued from 2009 to 2024, so quite a lift, and almost 900 patients underwent randomization to the exercise group or the health education group. And at almost 8 years of follow-up, we saw that the disease-free survival was significantly longer in the exercise group than the health education group. This was essentially 80.3% of patients were disease-free in exercise and 73.9% in the health education group. So a difference of over 6 percentage points, which, you know, at least in the breast cancer world, we make decisions about whether to do chemotherapy or not based on these kind of data. We also looked at overall survival in the exercise group and health education group, and the 8-year overall survival was 90.3% in the exercise group and 83.2% in the health education group. So this was a difference of 7.1%. Still statistically significant. I think this was really a fantastic effort over more than a decade at over 50 institutions with almost 900 patients, really done in a very systematic, high-intervention way that showed a fantastic result. Absolutely generalizable for patients with colon cancer. We have hints in other cancers that this is beneficial, and frankly, for our patients for other comorbidities, such as cardiovascular, etc., I really think that this is an abstract that deserved the press that it received. Dr. Sweetenham: Yeah, absolutely, and it is going to be very interesting, I think, over the next 2 or 3 years to see how much impact this particular study might have on programs across the country and across the world actually, in terms of what they do in this kind of adjuvant setting for structured exercise. Dr. Hamilton: Absolutely.  So let's move on to Abstract 3006. This was an NCI-led effort comparing genomic testing using ctDNA and tissue from patients with less common cancers who were enrolled in but not eligible for a treatment arm of the NCI-MATCH trial. Tell us about your takeaways from this study. Dr. Sweetenham: Yeah, so I thought this was a really interesting study based, as you said, on NCI-MATCH. And many of the listeners will probably remember that the original NCI-MATCH study screened almost 6,000 patients to assess eligibility for those who had an actionable mutation. And it turned out that about 60% of the patients who went on to the study had less common tumors, which were defined as anything other than colon, rectum, breast, non–small cell lung cancer, or prostate cancer. And most of those patients lacked an eligible mutation of interest and so didn't get onto a trial therapy. But with a great deal of foresight, the study group had actually collected plasma samples from these patients so that they would have the opportunity to look at circulating tumor DNA profiles with the potential being that this might be another way for testing for clinically relevant mutations in some of these less common cancer types. So initially, they tested more than 2,000 patients, and to make a somewhat complicated story short, there was a subset of five histologies with a larger representation in terms of sample size. And these were cholangiocarcinoma, small cell lung cancer, esophageal cancer, pancreatic, and salivary gland cancer. And in those particular tumors, when they compared the ctDNA sequencing with the original tumor, there was a concordance there of around 84%, 85%. And in the presentation, the investigators go on to list the specific mutated genes that were identified in each of those tumors. But I think that the other compelling part of this study from my perspective was not just that concordance, which suggests that there's an opportunity there for the use of ctDNA instead of tumor biopsies in some of these situations, but what was also interesting was the fact that there were several clinically relevant mutations which were detected only in the circulating tumor DNA. And a couple of examples of those included IDH1 for cholangiocarcinoma, BRAF and p53 in several histologies, and microsatellite instability was most prevalent in small cell lung cancer in the ctDNA. So I think that what this demonstrates is that liquid biopsy is certainly a viable screening option for patients who are being assessed for matching for targeted therapies in clinical trials. The fact that some of these mutations were only seen in the ctDNA and not in the primary tumor specimen certainly suggests that there's some tumor heterogeneity. But I think that for me, the most compelling part of this study was the fact that many of these mutations were only picked up in the plasma. And so, as the authors concluded, they believe that a comprehensive gene profiling with circulating tumor DNA probably should be included as a primary screening modality in future trials of targeted therapy of this type. Dr. Hamilton: Yeah, I think that that's really interesting and mirrors a lot of data that we've been seeing. At least in breast cancer, you know, we still do a biopsy up front to make sure that our markers, we're still treating the right disease that we think we are. But it really speaks to the utility of using ctDNA for serial monitoring and the emergence of mutations. Dr. Sweetenham: Absolutely. And you mentioned breast cancer, and so I'd like to dwell on that for a moment here because obviously, there was a huge amount of exciting breast cancer data presented at the meeting this year. And in particular, I'd like to ask you about LBA1008, the DESTINY-Breast09 clinical trial, which I think has the potential to establish a new first-line standard of care for metastatic HER2+ breast cancer. And that's an area where we haven't seen a whole lot of innovation for around a decade now. So can you give us some of the highlights of this trial and what your thinking is, having seen the results? Dr. Hamilton: Yeah, absolutely. So this was a trial in the first-line metastatic HER2 setting. So this was looking at trastuzumab deruxtecan. We certainly have had no shortage of reports around this drug, initially approved for later lines. DESTINY-Breast03 brought it into our second-line setting for HER2+ disease and we're now looking at DESTINY-Breast09 in first-line. So this actually was a 3-arm trial where patients were randomized 1:1:1 against standard taxane/trastuzumab/pertuzumab in one arm; trastuzumab deruxtecan with pertuzumab in another arm; and then a third arm, trastuzumab deruxtecan alone. And what we did not see reported was that trastuzumab deruxtecan-alone arm. But we did have reports from the trastuzumab deruxtecan plus pertuzumab versus the chemo/trastuzumab/pertuzumab. And what we saw was a statistically significant improvement in median progression-free survival, 26.9 months up to 40.7, so an improvement of 13.8 months, over a year in PFS. Not to mention that we're now in the 40-month range for PFS in first-line disease. Really, across all subgroups, we really weren't able to pick out a subset of patients that did not benefit. We did see about a 12% ILD rate with trastuzumab deruxtecan. That really is on par with what we've seen in other studies, around 10%-15%. I think that this is going to become a new standard of care in the first-line. I think it did leave some unanswered questions. We saw some data from the PATINA trial this past San Antonio Breast, looking at the addition of endocrine therapy with or without a CDK4/6 inhibitor, palbociclib, for those patients that also have ER+ disease, after taxane has dropped out in the first-line setting. So how we're going to kind of merge all this together is, I suspect that there are going to be patients that we or they just don't have the appetite to continue 3 to 4 years of trastuzumab deruxtecan. And so we're probably going to be looking at a maintenance-type strategy for them, maybe integrating the PATINA data there. But how we really put this into practice in the first-line setting and if or when we think about de-escalating down from trastuzumab deruxtecan to antibody therapy are some lingering questions. Dr. Sweetenham: Okay, so certainly is going to influence practice, but watch this space for a little bit longer, it sounds as though that's what you're saying. Dr. Hamilton: Absolutely.  So let's move on to GI cancer. Abstract 4006 reported preliminary results from the randomized phase 2 study of elraglusib in combination with gemcitabine/nab-paclitaxel versus the chemo gemcitabine/nab-paclitaxel alone in patients with previously untreated metastatic pancreatic cancer. Can you tell us more about this study? Dr. Sweetenham: Yeah, absolutely. As you mentioned, elraglusib is actually a first-in-class inhibitor of GSK3-beta, which has multiple potential actions in pancreatic cancer. But the drug itself may be involved in mediating drug resistance as well as in some tumor immune response modulation. Some of that's not clearly understood, I believe, right now. But certainly, preclinical data suggests that the drug may be effective in preclinical models and may also be effective in combination with chemotherapy and potentially with immune-modulating agents as well. So this particular study, as you said, was an open-label, randomized phase 2 study in which patients with pancreatic cancer were randomized 2:1 in favor of the elraglusib plus GMP—gemcitabine and nab-paclitaxel—versus the chemotherapy alone. And upon completion of the study, which is not right now, median overall survival was the primary end point, but there are a number of other end points which I'll talk about in just a moment. But the sample size was planned to be around 207 patients. The primary analysis included 155 patients in the combination arm versus 78 patients in the gemcitabine/nab-paclitaxel arm. Overall, the 1-year overall survival rate was 44.1% for the patients in the elraglusib-containing arm versus 23.0% in the patients receiving gemcitabine/nab-paclitaxel only. When they look at the median overall survival, it was 9.3 months for the experimental arm versus 7.2 months for chemotherapy alone. So put another way, there's around a 37% reduction in the risk of death with the use of this combination arm. The treatment was overall well-tolerated. There were some issues with grade 1 to 2 transient visual impairment in a large proportion of the patients. The most common treatment-related adverse effects with the elraglusib/GMP combination was transient visual impairment, which affected around 60% of the patients. Most of the more serious treatment-related adverse events included neutropenia, anemia, and fatigue in 50%, 25%, and 16% of the patients, respectively. So the early results from this study show a significant benefit for 1-year overall survival and for median overall survival with, as I mentioned above, a significant reduction in the risk of death. The authors went on to mention that the median overall survival for the control arm in this study is somewhat lower than in other comparable trials, but they think that this may be related to a more advanced disease burden in this particular study. Of interest to me was that right now: there is no apparent difference in progression-free survival between the 2 arms of this study. The authors described this as potentially indicating that this may be related in some way to immune modulation and immune effects on the tumor, which, if I'm completely honest, I don't totally understand. And so, the improvement in overall survival, as far as I can see at the moment, is not matched by an improvement in progression-free survival. So I think we probably need to wait for more time to elapse to see what happens with the study. And so, I think it certainly is an interesting study, and the results are intriguing, but I think it's probably a little early for it to actually shift the treatment paradigm in this disease. Dr. Hamilton: Fantastic. I think we've been waiting for advances in pancreatic cancer for a long time, but this, not unlike others, we learn more and then learn more we don't realize, so. Dr. Sweetenham: Right. Let's shift gears at this point and talk about a couple of other abstracts in kind of a very different space. Let's start out with symptom management for older adults with cancer. We know that undertreated symptoms are common among the older patient population, and Abstract 11002 reported on a randomized trial that demonstrated the effects of remote monitoring for older patients with cancer in terms of kind of symptoms and so on. Can you tell us a little bit about this study and whether you think this approach will potentially improve care for older patients? Dr. Hamilton: Yeah, I really liked this abstract. It was conducted through the Veterans Affairs, and it was based in California, which I'm telling you that because it's going to have a little bit of an implication later on. But essentially, adults that were 75 years or older who were Medicare Advantage beneficiaries were eligible to participate. Forty-three clinics in Southern California and Arizona, and patients were randomized either into a control group of usual clinic care alone, or an intervention group, which was usual care plus a lay health worker-led proactive telephone-based weekly symptom assessment, and this was for 12 months using the validated Edmonton Symptom Assessment System. So, there was a planned enrollment of at least 200 patients in each group. They successfully met that. And this lay health worker reviewed assessments with a physician assistant, who conducted follow-up for symptoms that changed by 2 points from a prior assessment or were rated 4 or greater. So almost a triage system to figure out who needed to be reached out to and to kind of work on symptoms. What I thought was fantastic about this was it was very representative of where it enrolled. There were actually about 50% of patients enrolled here that were Hispanic or Latinos. So some of our underserved populations and really across a wide variety of tumor types. They found that the intervention group had 53% lower odds of emergency room use, 68% lower odds of hospital use than the control group. And when they translated this to actual total cost of care, this was a savings of about $12,000 U.S. per participant and 75% lower odds of a death in an acute care facility. So I thought this was really interesting for a variety of reasons. One, certainly health care utilization and cost, but even more so, I think any of our patients would want to prevent hospitalizations and ER visits. Normally, that's not a fantastic experience having to feel poorly enough that you're in the emergency room or the hospital. And really showing in kind of concrete metrics that we were able to decrease this with this intervention. In terms of sustainability and scalability, I think the question is really the workforce to do this. Obviously, you know, this is going to take dedicated employees to have the ability to reach out to these patients, etc., but I think in value-based care, there's definitely a possibility of having reimbursement and having the funds to institute a program like this. So, definitely thought-provoking, and I hope it leads to more interventions. Dr. Sweetenham: Yeah, we've seen, over several years now, many of these studies which have looked at remote symptom monitoring and so on in this patient population, and many of them do show benefits for that in kinds of end points, not the least in this study being hospitalization and emergency room avoidance. But I think the scalability and personnel issue is a huge one, and I do wonder at some level whether we may see some AI-based platforms coming along that could actually help with this and provide interactions with these patients outside of actual real people, or at least in combination with real people. Dr. Hamilton: Yeah, that's a fantastic point.  So let's talk a little bit about clinical trials. So eligibility assessment for oncology clinical trials, or prescreening, really relies on manual review of unstructured clinical notes. It's time-consuming, it's prone to errors, and Abstract 1508 reported on the final analysis of a randomized trial that looked at the effect of human-AI teams prescreening for clinical trial eligibility versus human-only or AI-only prescreening. So give us more good news about AI. What did the study find? Dr. Sweetenham: Yeah, this is a really, a really interesting study. And of course, any of us who have ever been involved in clinical trials will know that accrual is always a problem. And I think most centers have attempted, and some quite successfully managed to develop prescreening programs so that patients are screened by a health care provider or health care worker prior to being seen in the clinic, and the clinical investigator will then already know whether they're going to be eligible for a trial or not. But as you've already said, it's a slow process. It's typically somewhat inefficient and requires a lot of time on the part of the health care workers to actually do this in a successful way. And so, this was a study from Emory University where they took three models of ways in which they could assess the accuracy of the prescreening of charts for patients who are going to be considered for clinical trials. One of these was essentially the regular way of having two research coordinators physically abstract the charts. The second one was an AI platform which would extract longitudinal EHR data. And then the third one was a combination of the two. So the AI would be augmented by the research coordinator or the other way around. As a gold standard, they had three independent oncology reviewers who went through all of these charts to provide what they regarded as being the benchmark for accuracy. In a way, it's not a surprise to me because I think that a number of other systems which have used this combination of human verification of AI-based tools, it actually ultimately concluded that the combination of the two in terms of chart accuracy was for the most part better than either one individually, either the research coordinator or the AI alone. So I'll give you just a few examples of where specifically that mattered. The human plus AI platform was more accurate in terms of tumor staging, in terms of identifying biomarker testing and biomarker results, as well as biomarker interpretation, and was also superior in terms of listing medications. There are one or two other areas where either the AI alone was somewhat more accurate, but the significant differences were very much in favor of a combination of human + AI screening of these patient charts. So, in full disclosure, this didn't save time, but what the authors reported was that there were definite efficiency gains, and presumably this would actually become even more improved once the research coordinators were somewhat more comfortable and at home with the AI tool. So, I thought it was an interesting way of trying to enhance clinical trial accrual up front by this combination of humans and technology, and I think it's going to be interesting to see if this gets adopted at other centers in the future. Dr. Hamilton: Yeah, I think it's really fascinating, all the different places that we can be using AI, and I love the takeaway that AI and humans together are better than either individually. Dr. Sweetenham: Absolutely.  Thanks once again, Dr. Hamilton, for sharing your insights with us today and for all of the incredible work you did to build a robust program. And also, congratulations on what was, I think, a really remarkable ASCO this year, one of the most exciting for some time, I think. So thank you again for that. Dr. Hamilton: Thanks so much. It was really a pleasure to work on ASCO 2025 this year. Dr. Sweetenham: And thank you to our listeners for joining us today. You'll find links to all the abstracts we discussed today in the transcript of this episode. Be sure to catch up on all of our coverage from the Annual Meeting. You can catch up on my daily reports that were published each day of the Annual Meeting, featuring the key science and innovations presented. And we'll have wrap-up episodes publishing in June, covering the full spectrum of malignancies from ASCO25. If you value the insights you hear on the ASCO Daily News Podcast, please remember 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.   More on today's speakers: Dr. John Sweetenham   Dr. Erika Hamilton @erikahamilton9   Follow ASCO on social media:  @ASCO on Twitter  ASCO on Bluesky  ASCO on Facebook   ASCO on LinkedIn     Disclosures:     Dr. John Sweetenham:     No relationships to disclose    Dr. Erika Hamilton: Consulting or Advisory Role (Inst): Pfizer, Genentech/Roche, Lilly, Daiichi Sankyo, Mersana, AstraZeneca, Novartis, Ellipses Pharma, Olema Pharmaceuticals, Stemline Therapeutics, Tubulis, Verascity Science, Theratechnologies, Accutar Biotechnology, Entos, Fosun Pharma, Gilead Sciences, Jazz Pharmaceuticals, Medical Pharma Services, Hosun Pharma, Zentalis Pharmaceuticals, Jefferies, Tempus Labs, Arvinas, Circle Pharma, Janssen, Johnson and Johnson   Research Funding (Inst): AstraZeneca, Hutchison MediPharma, OncoMed, MedImmune, Stem CentRx, Genentech/Roche, Curis, Verastem, Zymeworks, Syndax, Lycera, Rgenix, Novartis, Millenium, TapImmune, Inc., Lilly, Pfizer, Lilly, Pfizer, Tesaro, Boehringer Ingelheim, H3 Biomedicine, Radius Health, Acerta Pharma, Macrogenics, Abbvie, Immunomedics, Fujifilm, eFFECTOR Therapeutics, Merus, Nucana, Regeneron, Leap Therapeutics, Taiho Pharmaceuticals, EMD Serono, Daiichi Sankyo, ArQule, Syros Pharmaceuticals, Clovis Oncology, CytomX Therapeutics, InventisBio, Deciphera, Sermonix Pharmaceuticals, Zenith Epigentics, Arvinas, Harpoon, Black Diamond, Orinove, Molecular Templates, Seattle Genetics, Compugen, GI Therapeutics, Karyopharm Therapeutics, Dana-Farber Cancer Hospital, Shattuck Labs, PharmaMar, Olema Pharmaceuticals, Immunogen, Plexxikon, Amgen, Akesobio Australia, ADC Therapeutics, AtlasMedx, Aravive, Ellipses Pharma, Incyte, MabSpace Biosciences, ORIC Pharmaceuticals, Pieris Pharmaceuticals, Pieris Pharmaceuticals, Pionyr, Repetoire Immune Medicines, Treadwell Therapeutics, Accutar Biotech, Artios, Bliss Biopharmaceutical, Cascadian Therapeutics, Dantari, Duality Biologics, Elucida Oncology, Infinity Pharmaceuticals, Relay Therapeutics, Tolmar, Torque, BeiGene, Context Therapeutics, K-Group Beta, Kind Pharmaceuticals, Loxo Oncology, Oncothyreon, Orum Therapeutics, Prelude Therapeutics, Profound Bio, Cullinan Oncology, Bristol-Myers Squib, Eisai, Fochon Pharmaceuticals, Gilead Sciences, Inspirna, Myriad Genetics, Silverback Therapeutics, Stemline Therapeutics

From Nurse to Oncology Sales: Catina Pitzen's Journey   What does it take to go from bedside nurse to top oncology sales rep? In this episode of Medical Sales U, I sit down with Catina Pitzen, Senior Oncology Sales Representative at Eisai and board member of the Columbus chapter of the Oncology Nursing Society.   Catina shares how her nursing roots—especially her love for labor and delivery—prepared her for success in one of the most complex areas of pharmaceutical sales.   We discuss the realities of breaking into oncology, the power of pre-call planning, and how her commitment to lifelong learning shapes her approach. Whether you're a nurse considering a new career or a sales professional exploring oncology, Catina's story is a powerful reminder that clinical experience and curiosity can open doors in medical sales.

In this episode of Molecule to Market, you'll go inside the outsourcing space of the global drug development sector with Adriana Herrera, CEO at Pierre Fabre Pharmaceuticals (USA). Your host, Raman Sehgal, discusses the pharmaceutical and biotechnology supply chain with Adriana, covering: Why Big Pharma is such a great training ground for future pharma leaders, and how a period living and working in Mexico defined her leadership style The reality of being purchased by a big pharma like Gilead, and retaining independence as the acquired company, Kite Pharma The opening of a market opportunity that led Adriana to her first CEO role, and how the role is pushing her outside of her comfort zone Why she is optimistic about the future of manufacturing and commercialising cell therapies - innovation will find a way, but it takes time How the current geopolitical environment is adding more risk and uncertainty to an industry plagued with risk... and how that may impact investments and supply chains Adriana leads the expansion of Pierre Fabre's US presence in precision oncology, cell therapy and rare diseases with an immediate focus on the commercialization of a groundbreaking allogenic cell therapy. Most recently, Adriana served as U.S. General Manager at Kite Pharma where she successfully commercialized the autologous CART-cell therapy portfolio and led the US commercial functions. Prior to that, her experience included a tenure at Eisai as Senior Vice President and commercial head for U.S. Oncology and high-impact leadership roles at Novartis Oncology including Vice President and Global Diseases Lead for Lung and Genitourinary cancers. Adriana commenced her career at Bristol Myers-Squibb. Please subscribe, tell your industry colleagues and join us in celebrating and promoting the value and importance of the global life science outsourcing space. We'd also appreciate a positive rating! Molecule to Market is also sponsored and funded by ramarketing, an international marketing, design, digital and content agency helping companies differentiate, get noticed and grow in life sciences.

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

This Oncology PER®Spectives™ podcast explores the role of EZH2 in metastatic castration-resistant prostate cancer (mCRPC) progression and its synergy with androgen receptor inhibitors. In this podcast, experts Neeraj Agarwal, MD, FASCO; Himisha Beltran, MD; and Maha Hussain, MD, FACP, FASCO, discuss the management of mCRPC. Acknowledgment of Educational Grant Support This activity is supported by an educational grant from Pfizer Inc. Accreditation/Credit Designation Physicians' Education Resource®, LLC, is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Physicians' Education Resource®, LLC, designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians' Education Resource®, LLC is approved by the California Board of Registered Nursing, Provider #16669, for 1.5 Contact Hours. Instructions on How to Receive Credit Listen to this podcast in its entirety. Go to gotoper.com/credit and enter code: 6947 Answer the evaluation questions. Request credit using the drop-down menu. You may immediately download your certificate. Today's faculty are: Neeraj Agarwal, MD, FASCO Professor of Medicine Senior Director for Clinical Research HCI Presidential Endowed Chair of Cancer Research Director, Center of Investigational Therapeutics Director, Genitourinary Oncology Program Huntsman Cancer Institute, University of Utah (NCI-CCC) Salt Lake City, UT Disclosures: Grant/Research Support (paid to institution): Arvinas, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Calithera, Celldex, Clovis, Crispr, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Gilead, GlaxoSmithKline, Immunomedics, Janssen, Lava, Merck, Nektar, Neoleukin, Novartis, Oric, Pfizer, Roche, Sanofi, Seagen, Takeda, Tra-con Himisha Beltran, MD Associate Professor of Medicine Director of Translational Research Within Medical Oncology Harvard Medical School Lank Center for Genitourinary Oncology and the Division of Molecular and Cellular Oncology Dana Farber Cancer Institute Boston, MA Disclosures: Grant/Research Support: Circle Pharma, Daiichi Sankyo, Novartis; Adviser: Amgen, AstraZeneca, Daiichi Sankyo, Novartis Maha Hussain, MD, FACP, FASCO Genevieve E. Teuton Professor of Medicine Professor, Medicine (Hematology/Oncology) Deputy Director Robert H. Lurie Comprehensive Cancer Center Northwestern University Feinberg School of Medicine Chicago, IL Disclosures: Advisory Board: AstraZeneca, Bayer, Convergent Therapeutics, Honoraria: AstraZeneca, Bayer The staff of Physicians' Education Resource®, LLC, have no relevant financial relationships with ineligible companies. PER® mitigated all COI for faculty, staff, and planners prior to the start of this activity by using a multistep process. Off-Label Disclosure and Disclaimer This activity may or may not discuss investigational, unapproved, or off-label use of drugs. Learners are advised to consult prescribing information for any products discussed. The information provided in this accredited activity is for continuing education purposes only and is not meant to substitute for the independent clinical judgment of a health care professional relative to diagnostic, treatment, or management options for a specific patient's medical condition. The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of PER® or any company that provided commercial support for this activity. Release Date May 14, 2025 Expiration Date May 14, 2026

Parkinson's: Diagnosis and Treatment Evaluation and Credit:  https://www.surveymonkey.com/r/medchat78 Target Audience             This activity is targeted toward primary care physicians and advanced providers. Statement of Need This podcast will provide an overview of the diagnosis and management of Parkinson's disease including screening guidelines to improve early recognition. In that early symptoms of Parkinson's disease can mimic other conditions, for early recognition a review of this will be highlighted. The goal of this podcast is to provide tools for early recognition and management to maintain a patient's quality of life. According to the Parkinson's Foundation, there are approximately 90,000 people in the U.S. diagnosed with Parkinson's each year, which represents significant increase.  Objectives  Define Parkinson's disease and highlight its prevalence. Explain the signs and symptoms of Parkinson's disease, including the moto and non-motor manifestations. Outline the diagnostic criteria for Parkinson's disease, including clinical evaluations, neurological exams and applicable testing. Discuss the management of Parkinson's disease symptoms, addressing pharmacological treatments, surgical options and multidisciplinary team strategies to optimize patient care. ModeratorGregory E. Cooper, M.D., Ph.D. Neurologist Chief of Adult Neurology and Director of the Memory Center Norton Neuroscience Institute Louisville, Kentucky SpeakerJason L. Crowell, M.D. Neurologist and Movement Disorders Specialist Norton Neuroscience Institute Louisville, Kentucky  Moderator and Planner Disclosures  The moderator, Gregory E. Cooper, M.D., Ph.D, discloses relevant financial relationships with Eli Lilly and Eisai as a principal investigator. The planners of this activity do not have any relevant financial relationships with ineligible companies to disclose.   Speaker DisclosureThe speaker, Jason L. Cromwell, M.D. discloses a relevant financial relationship with the ineligible company AbbVie as a consultant and CND Life Services in research.  All relevant financial relationships have been successfully mitigated. Commercial Support There was no commercial support for this activity.    Physician Credits Accreditation Norton Healthcare is accredited by the Kentucky Medical Association to provide continuing medical education for physicians. Designation Norton Healthcare designates this enduring material for a maximum of .50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Nursing CreditsNorton Healthcare Institute for Education and Development is approved as a provider of nursing continuing professional development by the South Carolina Nurses Association, an accredited approver by the American Nurses Credentialing Center's Commission on Accreditation. This continuing professional development activity has been approved for 0.50 ANCC CE contact hours.  In order for nursing participants to obtain credits, they must claim attendance by attesting to the number of hours in attendance.  For more information related to nursing credits, contact Sally Sturgeon, DNP, RN, SANE-A, AFN-BC at (502) 446-5889 or sally.sturgeon@nortonhealthcare.org. Resources for Additional Study/References  Perspectives of People At-Risk on Parkinson's Prevention Research https://pubmed.ncbi.nlm.nih.gov/38489198/ Risk of Parkinson Disease Among Adults With vs Without Posttraumatic Stress Disorder https://pubmed.ncbi.nlm.nih.gov/35925604/ Date of Original Release | May 2025; Information is current as of the time of recording.  Course Termination Date | May 2028 Contact Information | Center for Continuing Medical Education; (502) 446-5955 or cme@nortonhealthcare.org Also listen to Norton Healthcare's podcast Stronger After Stroke. This podcast, produced by the Norton Neuroscience Institute, discusses difficult topics, answers frequently asked questions and provides survivor stories that provide hope. Norton Healthcare, a not for profit health care system, is a leader in serving adult and pediatric patients throughout Greater Louisville, Southern Indiana, the commonwealth of Kentucky and beyond. More information about Norton Healthcare is available at NortonHealthcare.com.  

Episode 114 - Eisai have developed a drug to help patients with Alzheimers - hear about how it works and the development process. Disclaimer: Please note that all information and content on the UK Health Radio Network, all its radio broadcasts and podcasts are provided by the authors, producers, presenters and companies themselves and is only intended as additional information to your general knowledge. As a service to our listeners/readers our programs/content are for general information and entertainment only.  The UK Health Radio Network does not recommend, endorse, or object to the views, products or topics expressed or discussed by show hosts or their guests, authors and interviewees.  We suggest you always consult with your own professional – personal, medical, financial or legal advisor. So please do not delay or disregard any professional – personal, medical, financial or legal advice received due to something you have heard or read on the UK Health Radio Network.