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Authors Drs. Jessica Ross and Alissa Cooper share insights into their JCO PO article, "Clinical and Pathologic Landscapes of Delta-Like Ligand 3 and Seizure-Related Homolog Protein 6 Expression in Neuroendocrine Carcinomas"  Host Dr. Rafeh Naqash and Drs. Ross and Cooper discuss the landscape of Delta-like ligand 3 (DLL3) and seizure-related homolog protein 6 (SEZ6) across NECs from eight different primary sites. TRANSCRIPT Dr. Rafeh Naqash: Hello and welcome to JCO Precision Oncology Conversations, where we bring you engaging conversations with authors of clinically relevant and highly significant JCO PO articles. I'm your host, Dr. Rafeh Naqash, podcast editor for JCO PO and an Associate Professor at the OU Health Stephenson Cancer Center. Today, I'm excited to be joined by Dr. Jessica Ross, third-year medical oncology fellow at the Memorial Sloan Kettering Cancer Center, as well as Dr. Alissa Cooper, thoracic medical oncologist at the Dana-Farber Cancer Institute and instructor in medicine at Harvard Medical School. Both are first and last authors of the JCO Precision Oncology article entitled "Clinical and Pathologic Landscapes of Delta-like Ligand 3 and Seizure-Related Homolog Protein 6 or SEZ6 Protein Expression in Neuroendocrine Carcinomas." At the time of this recording, our guest disclosures will be linked in the transcript. Jessica and Alissa, welcome to our podcast, and thank you for joining us today. Dr. Jessica Ross: Thanks very much for having us. Dr. Alissa Cooper: Thank you. Excited to be here. Dr. Rafeh Naqash: It's interesting, a couple of days before I decided to choose this article, one of my GI oncology colleagues actually asked me two questions. He said, "Rafeh, do you know how you define DLL3 positivity? And what is the status of DLL3 positivity in GI cancers, GI neuroendocrine carcinomas?" The first thing I looked up was this JCO article from Martin Wermke. You might have seen it as well, on obrixtamig, a phase 1 study, a DLL3 bi-specific T-cell engager. And they had some definitions there, and then this article came along, and I was really excited that it kind of fell right in place of trying to understand the IHC landscape of two very interesting targets. Since we have a very broad and diverse audience, especially community oncologists, trainees, and of course academic clinicians and some people who are very interested in genomics, we'll try to make things easy to understand. So my first question for you, Jessica, is: what is DLL3 and SEZ6 and why are they important in neuroendocrine carcinomas? Dr. Jessica Ross: Yeah, good question. So, DLL3, or delta-like ligand 3, is a protein that is expressed preferentially on the tumor cell surface of neuroendocrine carcinomas as opposed to normal tissue. It is a downstream target of ASCL1, and it's involved in neuroendocrine differentiation, and it's an appealing drug target because it is preferentially expressed on tumor cell surfaces. And so, it's a protein, and there are several drugs in development targeting this protein, and then Tarlatamab is an approved bi-specific T-cell engager for the treatment of extensive-stage small cell lung cancer in the second line. SEZ6, or seizure-like homolog protein 6, is a protein also expressed on neuroendocrine carcinoma cell surface. Interestingly, so it's expressed on neuronal cells, but its exact role in neuroendocrine carcinomas and oncogenesis is actually pretty poorly understood, but it was identified as an appealing drug target because, similarly to DLL3, it's preferentially expressed on the tumor cell surface. And so this has also emerged as an appealing drug target, and there are drugs in development, including antibody-drug conjugates, targeting this protein for that reason. Dr. Alissa Cooper: Over the last 10 to 15 years or so, there's been an increasing focus on precision oncology, finding specific targets that actually drive the cancer to grow, not just within lung cancer but in multiple other primary cancers. But specifically, at least speaking from a thoracic oncology perspective, the field of non-small cell lung cancer has completely exploded over the past 15 years with the discovery of driver oncogenes and then matched targeted therapies. Within the field of neuroendocrine carcinomas, including small cell lung cancer but also other high-grade neuroendocrine carcinomas, there has not been the same sort of progress in terms of identifying targets with matched therapies. And up until recently, we've sort of been treating these neuroendocrine malignancies kind of as a monolithic disease process. And so recently, there's been sort of an explosion of research across the country and multiple laboratories, multiple people converging on the same open questions about why might patients with specific tumor biologies have different kind of responses to different therapies. And so first this came from, you know, why some patients might have a good response to chemo and immunotherapy, which is the first-line approved therapy for small cell lung cancer, and we also sort of extrapolate that to other high-grade neuroendocrine carcinomas. What's the characteristic of that tumor biology? And at the same time, what are other targets that might be identifiable? Just as Jesse was saying, they're expressed on the cell surface, they're not necessarily expressed in normal tissue. Might this be a strategy to sort of move forward and create smarter therapies for our patients and therefore move really into a personalized era for treatment for each patient? And that's really driving, I think, a lot of the synthesis of this work of not only the development of multiple new therapies, but really understanding which tumor might be the best fit for which therapy. Dr. Rafeh Naqash: Thank you for that explanation, Alissa. And as you mentioned, these are emerging targets, some more further along in the process with approved drugs, especially Tarlatamab. And obviously, DLL3 was something identified several years back, but drug development does take time, and readout for clinical trials takes time. Could you, for the sake of our audience, try to talk briefly about the excitement around Tarlatamab in small cell lung cancer, especially data that has led to the FDA approval in the last year, year and a half? Dr. Alissa Cooper: Sure. Yeah, it's really been an explosion of excitement over, as you're saying, the last couple of years, and work really led by our mentor, Charlie Rudin, had identified DLL3 as an exciting target for small cell lung cancer specifically but also potentially other high-grade neuroendocrine malignancies. Tarlatamab is a DLL3-targeting bi-specific T-cell engager, which targets DLL3 on the small cell lung cancer cells as well as CD3 on T cells. And the idea is to sort of introduce the cancer to the immune system, circumventing the need for MHC class antigen presentation, which that machinery is typically not functional in small cell lung cancer, and so really allowing for an immunomodulatory response, which had not really been possible for most patients with small cell lung cancer prior to this. Tarlatamab was tested in a phase 2 registrational trial of about 100 patients and demonstrated a response rate of 40%, which was very exciting, especially compared with other standard therapies which were available for small cell lung cancer, which are typically cytotoxic therapies. But most excitingly, more than even the response rate, I think, in our minds was the durability of response. So patients whose disease did have a response to Tarlatamab could potentially have a durable response lasting a number of months or even over a year, which had previously not ever been seen in this in the relapsed/refractory setting for these patients. I think the challenge with small cell lung cancer and other high-grade neuroendocrine malignancies is that a response to therapy might be a bit easier to achieve, but it's that durability. The patient's tumors really come roaring back quite aggressively pretty quickly. And so this was sort of the most exciting prospect is that durability of response, that long potential overall survival tail of the curve really being lifted up. And then most recently at ASCO this year, Dr. Rudin presented the phase 3 randomized controlled trial which compared Tarlatamab to physician's choice of chemotherapy in a global study. And the choice of chemotherapy did vary depending on the part of the world that the patients were enrolled in, but in general, it was a really markedly positive study for response rate, for progression-free survival, and for overall survival. Really exciting results which really cemented Tarlatamab's place as the standard second-line therapy for patients with small cell lung cancer whose disease has progressed on first-line chemo-immunotherapy. So that has been very exciting. This drug was FDA approved in May of 2024, and so has been used extensively since then. I think the adoption has been pretty widespread, at least in the US, but now in this global trial that was just presented, and there was a corresponding New England Journal paper, I think really confirms that this is something we really hopefully can offer to most of our patients. And I think, as we all know, that this therapy or other therapies like it are also being tested potentially in the first-line setting. So there was data presented with Tarlatamab incorporated into the maintenance setting, which also showed exciting results, albeit in a phase 1 trial, but longer overall survival than we're used to seeing in this patient population. And we await results of the study that is incorporating Tarlatamab into the induction phase with chemotherapy as well. So all of this is extraordinarily exciting for our patients to sort of move the needle of how many patients we can keep alive, feeling functional, feeling well, for as long as possible. Dr. Rafeh Naqash: Very exciting session at ASCO. I was luckily one of the co-chairs for the session that Dr. Rudin presented it, and I remember somebody mentioning there was more progress seen in that session for small cell lung cancer than the last 30, 35 years for small cell, very exciting space and time to be in as far as small cell lung cancer. Now going to this project, Jessica, since you're the first author and Alissa's the last, I'm assuming there was a background conversation that you had with Alissa before you embarked on this project as an idea. So could you, again, for other trainees who are interested in doing research, and it's never easy to do research as a resident and a fellow when you have certain added responsibilities. Could you give us a little bit of a background on how this started and why you wanted to look at this question? Dr. Jessica Ross: Yeah, sure. So, as with many exciting research concepts, I think a lot of them are derived from the clinic. And so I think Alissa and I both see a good number of patients with small cell, large cell lung cancer, and then high-grade neuroendocrine carcinomas. And so I think this was really born out of a basic conversation of we have these drugs in development targeting these two proteins, DLL3 and SEZ6, but really what is the landscape of cancers that express these proteins and who are the patients that really might benefit from these exciting new therapies. And of course, there was some data out there, but sort of less than one would imagine in terms of, you know, neuroendocrine carcinomas can really come from anywhere in the body. And so when you're seeing a patient with small cell of the cervix, for example, like what are the chances that their cancer expresses DLL3 or expresses SEZ6? So it was really derived from this pragmatic, clinically oriented question that we had both found ourselves thinking about, and we were lucky enough at MSK, we had started systematically staining patients' tumors for DLL3, tumors that are high-grade neuroendocrine carcinomas, and then we had also more recently started staining for SEZ6 as well. And so we had this nice prospectively collected dataset with which to answer this question. Dr. Rafeh Naqash: Excellent. And Alissa, could you try to go into some of the details around which patients you chose, how many patients, what was the approach that you selected to collect the data for this project? Dr. Alissa Cooper: This is perhaps a strength but also maybe a limitation of this dataset is, as Jesse alluded to, our pathology colleagues are really the stars of this paper here because we were lucky enough at MSK that they were really forethinking. They are absolute experts in the field and really forward-thinking people in terms of what information might be needed in the future to drive treatment decision-making. And so, as Jesse had said, small cell lung cancer tumor samples reflexively are stained for DLL3 and SEZ6 at MSK if there's enough tumor tissue. The other high-grade neuroendocrine carcinomas, those stains are performed upon physician request. And so that is a bit of a mixed bag in terms of the tumor samples we were able to include in this dataset because, you know, upon physician request depends on a number of factors, but actually at MSK, a number of physicians were requesting these stains to be done on their patients with high-grade neuroendocrine cancers of of other histologies. So we looked at all tumor samples with a diagnosis of high-grade neuroendocrine carcinoma of any histology that were stained for these two stains of interest. You know, I can let Jesse talk a bit more about the methodology. She was really the driver of this project. Dr. Jessica Ross: Yeah, sure. So we had 124 tumor samples total. All of those were stained for DLL3, and then a little less than half, 53, were stained for SEZ6. As Alissa said, they were from any primary site. So about half of them were of lung origin, that was the most common primary site, but we included GI tract, head and neck, GU, GYN, even a few tumors of unknown origin. And again, that's because I think a lot of these trials are basket trials that are including different high-grade neuroendocrine carcinomas no matter the primary site. And so we really felt like it was important to be more comprehensive and inclusive in this study. And then, methodologically, we also defined positivity in terms of staining of these two proteins as anything greater than or equal to 1% staining. There's really not a defined consensus of positivity when it comes to these two novel targets and staining for these two proteins. But in the Tarlatamab trials, for some of the correlative work that's been done, they use that 1% cutoff, and we just felt like being consistent with that and also using a sort of more pragmatic yes/no cutoff would be more helpful for this analysis. Dr. Alissa Cooper: And that was a point of discussion, actually. We had contemplated multiple different schemas, actually, for how to define thresholds of positivity. And I know you brought up that question before, what does it mean to be DLL3 positive or DLL3 high? I think you were alluding to prior that there was a presentation of obrixtamig looking at extra-pulmonary neuroendocrine carcinomas, and they actually divvied up the results between DLL3 50% or greater versus DLL3 low under 50%. And they actually did demonstrate differential efficacy certainly, but also some differential safety as well, which is very provocative and that kind of analysis has not been presented for other novel therapies as far as I'm aware. I could be wrong, but as far as I'm aware, that was sort of the first time that we saw a systematic presentation of considering patients to be, quote unquote, "high" or "low" in these sort of novel targets. I think it is important because the label for Tarlatamab does not require any DLL3 expression at all, actually. So it's not hinging upon DLL3 expression. They depend on the fact that the vast majority of small cell lung cancer tumors do express DLL3, 85% to 90% is what's been demonstrated in a few studies. And so, there's not prerequisite testing needed in that regard, but maybe for these extra-pulmonary, other histology neuroendocrine carcinomas, maybe it does matter to some degree. Dr. Rafeh Naqash: Definitely agree that this evolving landscape of trying to understand whether an expression for something actually really does correlate with, whether it's an immune cell engager or an antibody-drug conjugate is a very evolving and dynamically moving space. And one of the questions that I was discussing with one of my friends was whether IHC positivity and the level of IHC positivity, as you've shown in one of those plots where you have double positive here on the right upper corner, you have the double negative towards the left lower, whether that somehow determines mRNA expression for DLL3. Obviously, that was not the question here that you were looking at, but it does kind of bring into question certain other aspects of correlations, expression versus IHC. Now going to the figures in this manuscript, very nicely done figures, very easy to understand because I've done the podcast for quite a bit now, and usually what I try to do first is go through the figures before I read the text, and and a lot of times it's hard to understand the figures without reading the text, but in your case, specifically the figures were very, very well done. Could you give us an overview, a quick overview of some of the important results, Jessica, as far as what you've highlighted in the manuscript? Dr. Jessica Ross: Sure. So I think the key takeaway is that, of the tumors in our cohort, the majority were positive for DLL3 and positive for SEZ6. So about 80% of them were positive for DLL3 and 80% were positive for SEZ6. About half of the tumors were stained for both proteins, and about 65% of those were positive as well. So I think if there's sort of one major takeaway, it's that when you're seeing a patient with a high-grade neuroendocrine carcinoma, the odds are that their tumor will express both of these proteins. And so that can sort of get your head thinking about what therapies they might be eligible for. And then we also did an analysis of some populations of interest. So for example, we know that non-neuroendocrine pathologies can transform into neuroendocrine tumors. And so we specifically looked at that subset of patients with transformed tumors, and those were also- the majority of them were positive, about three-quarters of them were positive for both of these two proteins. We looked at patients with brain met samples, again, about 70% were positive. And then I'd say the last sort of population of interest was we had a subset of 10 patients who had serial biopsies stained for either DLL3 or SEZ6 or both. In between the two samples, these patients were treated with chemotherapy. They were not treated with targeted therapy, but interestingly, in the majority of cases, the testing results were concordant, meaning if it was DLL3 positive to begin with, it tended to remain DLL3 positive after treatment. And so I think that's important as well as we think about, you know, a patient who maybe had DLL3 testing done before they received their induction chemo-IO, we can somewhat confidently say that they're probably still DLL3 positive after that treatment. And then finally, we did do a survival analysis among specifically the patients with lung neuroendocrine carcinomas. We looked at whether DLL3 expression affected progression-free survival on first-line platinum-etoposide, and then we looked at did it affect overall survival. And we found that it did not have an impact or the median progression-free survival was similar whether you were DLL3 positive or negative. But interestingly, with overall survival, we found that DLL3 positivity actually correlated with slightly improved overall survival. These were small numbers, and so, you know, I think we have to interpret this with caution, for sure, but it is interesting. I think there may be something to the fact that five of the patients who were DLL3 positive were treated with DLL3-targeting treatments. And so this made me think of, like in the breast cancer world, for example, if you have a patient with HER2-positive disease, it initially portended worse prognosis, more aggressive disease biology, but on the other hand, it opens the door for targeted treatments that actually now, at least with HER2-positive breast cancer, are associated with improved outcomes. And so I think that's one finding of interest as well. Dr. Rafeh Naqash: Definitely proof-of-concept findings here that you guys have in the manuscript. Alissa, if I may ask you, what is the next important step for a project like this in your mind? Dr. Alissa Cooper: Jesse has highlighted a couple of key findings that we hope to move forward with future investigative studies, not necessarily in a real-world setting, but maybe even in clinical trial settings or in collaboration with sponsors. Are these biomarkers predictive? Are they prognostic? You know, those are still- we have some nascent data, data has been brewing, but I think that we we still don't have the answers to those open questions, which I think are critically important for determining not only clinical treatment decision-making, but also our ability to understand sequencing of therapies, prioritization of therapies. I think a prospective, forward-looking project, piggybacking on that paired biopsy, you know, we had a very small subset of patients with paired biopsies, but a larger subset or cohort looking at paired biopsies where we can see is there evolution of these IHC expression, even mRNA expression, as you're saying, is there differential there? Are there selection pressures to targeted therapies? Is there upregulation or downregulation of targets in response not just to chemotherapy, but for example, for other sort of ADCs or bi-specific T-cell engagers? I think those are going to be critically important future studies which are going to be a bit challenging to do, but really important to figure out this key clinical question of sequencing, which we're all contemplating in our clinics day in and day out. If you have a patient, and these patients often can be sick quite quickly, they might have one shot of what's the next treatment that you're going to pick. We can't guarantee that every patient is going to get to see every therapy. How can you help to sort of answer the question of like what should you offer? So I think that's the key question sort of underlying any future work is how predictive or prognostic are these biomarkers? What translational or correlative studies can we do on the tissue to understand clinical treatment decision-making? I think those are the key things that will unfold in the next couple of years. Dr. Rafeh Naqash: The last question for you, Alissa, that I have is, you are fairly early in your career, and you've accomplished quite a lot. One of the most important things that comes out from this manuscript is your mentorship for somebody who is a fellow and who led this project. For other junior investigators, early-career investigators, how did you do this? How did you manage to do this, and how did you mentor Jessica on this project with some of the lessons that you learned along the way, the good and other things that would perhaps help other listeners as they try to mentor residents, trainees, which is one of the important things of what we do in our daily routine? Dr. Alissa Cooper: I appreciate you calling me accomplished. Um, I'm not sure how true that is, but I appreciate that. I didn't have to do a whole lot with this project because Jesse is an extraordinarily smart, driven, talented fellow who came up with a lot of the clinical questions and a lot of the research questions as well. And so this project was definitely a collaborative project on both of our ends. But I think what was helpful from both of our perspectives is from my perspective, I could kind of see that this was a gap in the literature that really, I think, from my work leading clinical trials and from treating patients with these kinds of cancers that I really hoped to answer. And so when I came to Jessica with this idea as sort of a project to complete, she was very eager to take it and run with it and also make it her own. You know, in terms of early mentorship, I have to admit this was the first project that I mentored, so it was a great learning experience for me as well because as an early-career clinician and researcher, you're used to having someone else looking over your shoulder to tell you, "Yes, this is a good journal target, here's what we can anticipate reviewers are going to say, here are other key collaborators we should include." Those kind of things about a project that don't always occur to you as you're sort of first starting out. And so all of that experience for me to be identifying those more upper-level management sort of questions was a really good learning experience for me. And of course, I was fantastically lucky to have a partner in Jesse, who is just a rising star. Dr. Jessica Ross: Thank you. Dr. Rafeh Naqash: Well, excellent. It sounds like the first of many other mentorship opportunities to come for you, Alissa. And Jessica, congratulations on your next step of joining and being faculty, hopefully, where you're training. Thank you again, both of you. This was very insightful. I definitely learned a lot after I reviewed the manuscript and read the manuscript. Hopefully, our listeners will feel the same. Perhaps we'll have more of your work being published in JCO PO subsequently. Dr. Alissa Cooper: Hope so. Thank you very much for the opportunity to chat today. Dr. Jessica Ross: Yes, thank you. This was great. Dr. Rafeh Naqash: Thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or review and be sure to subscribe so as you never miss an episode. You can find all ASCO shows at asco.org/podcasts. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Disclosures: Dr. Alissa Jamie Cooper Honoraria Company: MJH Life Scienes, Ideology Health, Intellisphere LLC, MedStar Health, Physician's Education Resource, LLC,  Gilead Sciences, Regeneron, Daiichi Sankyo/Astra Zeneca, Novartis,  Research Funding: Merck, Roche, Monte Rosa Therapeutics, Abbvie, Amgen, Daiichi Sankyo/Astra Zeneca Travel, Accommodations, Expenses: Gilead Sciences

Discover how innovative drip irrigation technologies are transforming water management and boosting efficiency in farming. Mike Hemman, Netafim Senior Vice President of North America, shares his journey from crop protection to leading irrigation solutions, highlighting the challenges and opportunities in modern agriculture. Tune in to explore the future of precision farming and the vital role of water conservation across the globe. *** Show Notes: Ag Solutions Network Socials: https://www.agsolutionsnetwork.com/agemergepodcast https://www.facebook.com/ASN.farm https://www.linkedin.com/company/agsolutionsnetwork https://twitter.com/POWER2GRO https://www.instagram.com/agsolutionsnetwork/ Ag Solutions Network website: https://www.agsolutionsnetwork.com/ Click to watch or listen and as always, let us know if you have any questions or guest ideas by emailing ​contactus@agsolutionsnetwork.com​. Chapters: 00:00:00 - Introduction to Drip Irrigation 00:06:00 - Mike Hemman's Journey 00:12:00 - Innovative Irrigation Solutions 00:18:00 - Water Conservation and Efficiency 00:24:00 - Future of Precision Farming 00:30:00 - Challenges in Water Management 00:36:00 - The Role of Technology in Agriculture 00:42:00 - Sustainable Farming Practices 00:48:00 - Netafim's Global Impact 00:54:00 - Closing Thoughts and Future Outlook *** *** Introducing the Ag Modernization Fund Water basins are strained across the nation, and while modern irrigation remains one of the fastest and most proven ways to improve water use efficiency, many farmers still face barriers to accessing the financing for installing the latest systems. To address this challenge, Orbia, Netafim USA along with California Water Resilience Initiative (CWRI), launched the Ag Modernization Fund, a first-of-its-kind investment vehicle that pools private-sector capital to directly fund irrigation upgrades for growers. Backed by Keurig Dr Pepper, Gilead Sciences, and General Mills, the fund closed in 2025 with $300,000, already supporting five farms spanning 200 acres. These projects, to be completed within the year, are projected to reduce water use by 491 acre-feet — nearly 159 million gallons annually, enough to fill 241 Olympic-sized pools. This fund is also listed on the UN-backed CEO Water Mandate's Water Action Hub, aligning with global sustainability goals to address water stress across 100 priority basins worldwide — 8 of which are in the United States. About Our Guest: Mike Hemman - SVP, Netafim North America Division Mike joined Netafim, Orbia Precision Agriculture business, in 2019 as the President of Netafim USA and was promoted to Senior Vice President of North America in 2024. He has been instrumental in driving strategic growth and expanding profit margins through innovative market strategies, customer segmentation, product lifecycle management, and improvements in supply chain and manufacturing efficiencies. With multiple decades of experience in the crop protection and seed industry, Mike has held key commercial leadership positions at DuPont, Corteva, and Pioneer Seed. His extensive background in biologicals, fertility, crop protection, seed, and irrigation give him a unique cross-sector perspective on the agricultural industry. Mike holds a Bachelor of Science degree in Plant Science from California State University, Fresno, where he also pursued Master of Science coursework in agronomy. He is currently a member of the Executive Board of the Irrigation Association and has previously served on the boards of the Agricultural Retailers Association, Western Plant Health Association, and California Association of Pest Control Advisers.

In this episode, Benjamin Levy, MD, FASCO, and Alex Spira, MD, PhD, FASCO, discuss the latest developments in targeting TROP2 and TIGIT for the treatment of lung cancer, including:TROP2-targeting ADCs: datopotamab deruxtecan, sacituzumab govitecan, sacituzumab tirumotecan TROP2 ADCS for patients with EGFR-mutated NSCLCTIGIT-targeting agents: domvanalimab, rilvegostomigPresenters:Benjamin Levy, MD, FASCOAssociate ProfessorJohns Hopkins School of MedicineClinical DirectorJohns Hopkins Kimmel Cancer Center, National Capitol Region (NCR)Washington, DCAlex Spira, MD, PhD, FASCODirector Clinical ResearchVirginia Cancer SpecialistsCEO NEXT Oncology VirginiaFairfax, VirginiaContent based on an online CME program supported by an independent educational grant from Gilead Sciences, Inc.Link to full program:https://bit.ly/4qZLR6B Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

Send us a textGood morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we're diving into several groundbreaking advancements and strategic shifts in the industry that promise to reshape the landscape of patient care and therapeutic innovations.The U.S. Food and Drug Administration has introduced a novel regulatory pathway aimed at expediting the approval process for custom gene-editing therapies. Articulated by FDA officials Vinay Prasad, M.D., and Martin Makary, M.D., this new approach is set to revolutionize personalized medicine, particularly for genetic disorders where tailored interventions are crucial. Gene editing technologies, like CRISPR-Cas9, have opened unprecedented avenues for addressing genetic conditions directly at their source. However, the regulatory framework has struggled to keep pace with these advances, often hampering innovation with lengthy and complex approval processes.This proposed pathway seeks to streamline these requirements by adopting a risk-based assessment model that considers the unique properties of gene-editing therapies. Unlike traditional drugs, which follow a uniform clinical trial path, gene-editing treatments require a more nuanced regulatory approach due to their precision and potential off-target effects. The framework emphasizes adaptive trial designs—allowing for modifications based on interim results—and integrates real-world data to create a dynamic regulatory process. This not only promises faster development times but also fosters innovation by making it easier for companies to bring cutting-edge therapies to market.The implications are far-reaching. For researchers and biotech firms, this represents a chance to reduce time-to-market significantly while maintaining high safety standards. It also sets a precedent for future regulatory models that prioritize patient-centric approaches, acknowledging the diverse genetic landscapes of individuals with rare diseases. On a broader scale, this shift underscores the increasing recognition of personalized medicine's potential to transform healthcare delivery.In parallel developments, Gilead Sciences has achieved positive phase 3 results for its single-tablet regimen combining bictegravir and lenacapavir for HIV treatment. This milestone offers hope for simplifying treatment protocols for patients currently on multi-tablet regimens, potentially enhancing adherence and improving health outcomes. Gilead's preparation for regulatory filings marks an essential step forward in their therapeutic portfolio.Turning to cancer treatment advancements, Kyowa Kirin's collaboration with Kura Oncology has led to FDA approval for an oral medication targeting a subset of acute myeloid leukemia patients. This approval highlights the power of strategic partnerships in expediting the development of targeted cancer therapies and brings new hope to patients with limited treatment options.Meanwhile, several pharmaceutical companies, including Fresenius, Sun Pharma, and Teva, have been involved in product recalls ranging from hospital drugs to antibiotics and ADHD medications. These recalls underscore ongoing challenges in maintaining drug safety standards and emphasize the need for rigorous quality control measures across the industry.Zealand Pharma has opted to pause development of its dual GLP-1/GLP-2 agonist, dapiglutide, due to an increasingly crowded metabolic disorder treatment landscape. By reallocating resources towards programs with greater clinical differentiation potential, Zealand reflects broader industry trends prioritizing investments in areas with clearer paths to market success.In malaria treatment advances, Novartis has achieved significant progress with its next-generation drug 'Ganlum,Support the show

Overview: In this episode, Dr Toyin Nwafor and Dr Andrew Zolopa provide an overview of the HIV treatment landscape both globally and in the United States. They highlight the current gaps in the HIV care continuum, emphasize the importance of rapid start and viral suppression in reducing HIV transmission through sex and describe initiatives and strategies aimed at closing these gaps to help end the HIV epidemic in the United States. The views expressed are those of the panelist(s) and not necessarily Gilead Sciences, Inc. The information provided in this podcast is not intended to be and should not be understood to provide medical advice. Listeners should note that our discussions in this episode are relevant to the USA only and may not be appropriate for other regions. This episode was recorded in August 2025 and the content reflects the information available at that time. Guest: Toyin Nwafor, MD; Andrew Zolopa, MD   For more information, please visit: https://www.pri-med.com/clinical-resources/curriculum/hiv-in-focus  References AETC. Rapid (immediate) ART initiation and restart: guide for clinicians. 2023. Available from: https://aidsetc.org/resource/rapid-immediate-art-initiation-restart-guide-clinicians (Accessed June 25, 2025). Baxter A et al. J Acquir Immune Defic Syndr 2025;99:47–54. CDC. About ending the HIV epidemic in the US. 2024. Available from: https://www.cdc.gov/ehe/php/about/index.html (Accessed June 25, 2025). CDC. Clinical testing guidance for HIV. 2025. Available from: https://www.cdc.gov/hivnexus/hcp/diagnosis-testing/index.html (Accessed June 25, 2025). CDC. Getting tested for HIV. 2025. Available from: https://www.cdc.gov/hiv/testing/index.html#cdc_testing_why_get_tested-why-get-tested (Accessed June 25, 2025). CDC. Laboratory testing for the diagnosis of HIV infection. 2014. Available from: https://stacks.cdc.gov/view/cdc/23446 (Accessed June 25, 2025). CDC. National HIV prevention and care objectives: 2025 update. 2025. Available from: https://www.cdc.gov/hiv-data/nhss/national-hiv-prevention-and-care-objectives-2025.html (Accessed June 25, 2025). Delaney KP et al. Am J Prev Med 2021;61(5 Suppl 1):S6–S15. DHHS. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. 2024. Available from: https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/adult-adolescent-arv/guidelines-adult-adolescent-arv.pdf (Accessed June 25, 2025). HIV.gov. EHE overview. 2025. Available from: https://www.hiv.gov/federal-response/ending-the-hiv-epidemic/overview (Accessed June 25, 2025). HIV.gov. Global statistics. 2025. Available from: https://www.hiv.gov/hiv-basics/overview/data-and-trends/global-statistics (Accessed June 25, 2025). HIV.gov. HIV Care Continuum. 2025. Available from: https://www.hiv.gov/federal-response/other-topics/hiv-aids-care-continuum (Accessed June 25, 2025). HIV.gov. Key EHE strategies. 2024. Available from: https://www.hiv.gov/federal-response/ending-the-hiv-epidemic/key-strategies (Accessed June 25, 2025). HIV.gov. US statistics. 2025. Available from: https://www.hiv.gov/hiv-basics/overview/data-and-trends/statistics (Accessed June 25, 2025). HIV.gov. Viral suppression and undetectable viral load. 2025. Available from: https://www.hiv.gov/hiv-basics/staying-in-hiv-care/hiv-treatment/viral-suppression (Accessed June 25, 2025). Mirzazadeh A et al. PLoS Med 2022;19:e1003940. NIH. HIV testing. 2025. Available from: https://hivinfo.nih.gov/understanding-hiv/fact-sheets/hiv-testing (Accessed June 25, 2025). Palacio-Vieira J et al. BMC Public Health 2021;21:1596. Saag MS et al. JAMA 2018;320:379–96. The White House. National HIV/AIDS strategy for the United States 2022–2025. 2021. Available from: https://files.hiv.gov/s3fs-public/NHAS-2022-2025.pdf (Accessed June 25, 2025). WHO. Supporting re-engagement in HIV treatment services: policy brief. 2024. Available from: https://www.who.int/publications/i/item/9789240097339 (Accessed June 25, 2025).

Overview: In this episode, Dr Gina Brown and Dr Sahar Khalili draw on their expertise in HIV prevention to provide an overview of the current PrEP landscape in the United States. They highlight advancements in HIV prevention and emphasize the importance of targeted programs to address disparities in access and uptake across population groups and geographic regions. The views expressed are those of the panelist(s) and not necessarily Gilead Sciences, Inc. The information provided in this podcast is not intended to be and should not be understood to provide medical advice. Listeners should note that our discussions in this episode are relevant to the USA only and may not be appropriate for other regions. This episode was recorded in August 2025 and the content reflects the information available at that time. Guest: Gina Brown, MD; Sahar Khalili, PharmD   For more information, please visit: https://www.pri-med.com/clinical-resources/curriculum/hiv-in-focus  References ACOG. Preexposure prophylaxis for the prevention of human immunodeficiency virus. 2024. Available from: https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2022/06/preexposure-prophylaxis-for-the-prevention-of-human-immunodeficiency-virus (Accessed June 25, 2025). ADAP Directory. About. 2024. Available from: https://adap.directory/about (Accessed June 25, 2025). Aidsmap. Condoms. 2023. Available from: https://www.aidsmap.com/about-hiv/condoms#toc-how-effective-are-condoms (Accessed June 25, 2025). AIDSVu. AIDSVu releases new PrEP data and launches PrEPVu.org, a new PrEP equity platform. 2024. Available from: https://aidsvu.org/news-updates/aidsvu-releases-new-prep-data-and-launches-prepvu-org-a-new-prep-equity-platform/ (Accessed June 25, 2025). AIDSVu.org was developed by the Rollins School of Public Health at Emory University in partnership with Gilead Sciences, Inc. AIDSVu. AIDSVu releases 2024 PrEP use data showing growing use across the U.S. 2025. Available from: https://aidsvu.org/news-updates/aidsvu-releases-2024-prep-use-data-showing-growing-use-across-the-u-s/ (Accessed July 18, 2025). AIDSVu.org was developed by the Rollins School of Public Health at Emory University in partnership with Gilead Sciences, Inc. AIDSVu. Location profiles: South. 2025. Available from: https://map.aidsvu.org/profiles/region/south/prevention-and-testing#1-2-PnR (Accessed July 31, 2025). AIDSVu.org was developed by the Rollins School of Public Health at Emory University in partnership with Gilead Sciences, Inc. AIDSVu. PrEP use significantly associated with decreasing new HIV diagnoses across U.S. states. 2025. Available from: https://aidsvu.org/news-updates/prep-use-significantly-associated-with-decreasing-new-hiv-diagnoses-across-u-s-states/ (Accessed June 25, 2025). AIDSVu.org was developed by the Rollins School of Public Health at Emory University in partnership with Gilead Sciences, Inc. Baeten J et al. Curr HIV/AIDS Rep 2013;10:142–51. Bekker LG et al. N Engl J Med 2024;391:1179–92. CDC. About ending the HIV epidemic in the US. 2024. Available from: https://www.cdc.gov/ehe/php/about/index.html (Accessed June 2, 2025). CDC. Clinical Guidance for PrEP. 2025. Available from: https://www.cdc.gov/hivnexus/hcp/prep/index.html (Accessed June 25, 2025). CDC. Preexposure prophylaxis for the prevention of HIV infection in the United States - 2021 update. 2021. Available from: https://stacks.cdc.gov/view/cdc/112360 (Accessed June 25, 2025). Coates TJ et al. Lancet 2008;372:669–84. DHHS. Pre-exposure (PrEP) to prevent HIV during periconception, antepartum, ad postpartum. 2024. Available from: https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/perinatal-hiv/pre-exposure-prophylaxis-prep-prevent-hiv-perinatal.pdf (Accessed June 25, 2025). Gandhi RT et al. JAMA 2023;329:63–84. HIV.gov. HIV treatment as prevention. 2023. Available from: https://www.hiv.gov/tasp (Accessed June 25, 2025). HIV.gov. Key EHE strategies. 2024. Available from: https://www.hiv.gov/federal-response/ending-the-hiv-epidemic/key-strategies (Accessed June 2, 2025). HIV.gov. Pre-exposure prophylaxis. 2025. Available from: https://www.hiv.gov/hiv-basics/hiv-prevention/using-hiv-medication-to-reduce-risk/pre-exposure-prophylaxis (Accessed June 25, 2025). Kelley CF et al. N Engl J Med 2025;392:1261–76. Kourtis AP et al. Ann Epidemiol 2025:106:48-54. Landers S et al. Am J Public Health 2017;107:1534–35. Landovitz RJ et al. N Engl J Med 2021;385:595–608. NIH. HIV and sexually transmitted infections (STIs). 2021. Available from: https://hivinfo.nih.gov/understanding-hiv/fact-sheets/hiv-and-sexually-transmitted-diseases-stds (Accessed June 25, 2025). NIH. HIV medicines during pregnancy and childbirth. 2025. Available from: https://hivinfo.nih.gov/understanding-hiv/fact-sheets/hiv-medicines-during-pregnancy-and-childbirth (Accessed July 31, 2025) NIH. Post-exposure prophylaxis (PEP). 2025. Available from: https://hivinfo.nih.gov/understanding-hiv/fact-sheets/post-exposure-prophylaxis-pep (Accessed June 25, 2025). NIH. PrEP to prevent HIV and promote sexual health. 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK556471/ (Accessed June 25 2025). Siegler AJ et al. Ann Epidemiol 2020;45:24–31.e37 Sullivan PS et al. J Int AIDS Soc 2025;28:e26459. Townes A et al. Obstet Gynecol 2023;143:294–301. Underhill K et al. PLoS Med 2007;4:e275. United States Census Bureau. National population by characteristics: 2020–2024. 2024. Available from: https://www.census.gov/data/tables/time-series/demo/popest/2020s-national-detail.html (Accessed June 25, 2025). Owens DK et al. JAMA 2019;321:2326–36. Vermund SH et al. J Acquir Immune Defic Syndr 2013;63:S12–25. Washington State Department of Health. Pre-exposure prophylaxis drug assistance program (PrEP DAP). Available from: https://doh.wa.gov/you-and-your-family/illness-and-disease-z/hiv/prevention/pre-exposure-prophylaxis-drug-assistance-program-prep-dap (Accessed June 25, 2025). World Health Organization. Global HIV programme: pre-exposure prophylaxis (PrEP). Available from: https://www.who.int/teams/global-hiv-hepatitis-and-stis-programmes/hiv/prevention/pre-exposure-prophylaxis (Accessed June 25, 2025).

Overview: In this episode, Toyin Nwafor, MD, and Christian B Ramers, MD, draw on their experience in primary care, HIV and HIV prevention to highlight missed opportunities for HIV prevention and discuss strategies to help address gaps in the HIV care continuum. The views expressed are those of the panelist(s) and not necessarily Gilead Sciences, Inc. The information provided in this podcast is not intended to be and should not be understood to provide medical advice. Listeners should note that our discussions in this episode are relevant to the USA only and may not be appropriate for other regions. This episode was recorded in August 2025 and the content reflects the information available at that time. Guest: Toyin Nwafor, MD; Christian B Ramers, MD, MPH, FIDSA, AAHIVS   For more information, please visit: https://www.pri-med.com/clinical-resources/curriculum/hiv-in-focus  References AIDSVu.org. Prevalence in the United States. 2022. Available from: https://map.aidsvu.org/ (Accessed June 25, 2025). AIDSVu.org was developed by the Rollins School of Public Health at Emory University in partnership with Gilead Sciences, Inc. Baeten J et al. Curr HIV/AIDS Rep 2013;10:142–51. CDC. Clinical testing guidance for HIV. 2025. Available from: https://www.cdc.gov/hivnexus/hcp/diagnosis-testing/index.html (Accessed June 25, 2025). CDC. Discussing sexual health with your patients. 2025. Available from: https://www.cdc.gov/hivnexus/hcp/sexual-history/index.html (Accessed June 25, 2025). CDC.gov. HIV diagnoses, deaths, and prevalence. 2025. Available from: https://www.cdc.gov/hiv-data/nhss/hiv-diagnoses-deaths-prevalence.html (Accessed June 25, 2025). CDC. National HIV prevention and care objectives: 2025 update. 2025. Available from: https://www.cdc.gov/hiv-data/nhss/national-hiv-prevention-and-care-objectives-2025.html (Accessed June 25, 2025). CDC. Preexposure prophylaxis for the prevention of HIV infection in the United States – 2021 update: a clinical practice guideline. 2021. Available from: https://stacks.cdc.gov/view/cdc/112360 (Accessed June 25, 2025). Doblecki-Lewis S et al. J Int Assoc Provid AIDS Care 2019;18:2325958219848848. DHHS. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. 2024. Available from: https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/adult-adolescent-arv/guidelines-adult-adolescent-arv.pdf (Accessed June 25, 2025). HIV.gov. Key EHE strategies. 2024. Available from: https://www.hiv.gov/federal-response/ending-the-hiv-epidemic/key-strategies (Accessed June 2, 2025). HIV.gov. HIV treatment as prevention. 2023. Available from: https://www.hiv.gov/tasp (Accessed June 25, 2025). HIV.gov. US statistics. 2025. Available from: https://www.hiv.gov/hiv-basics/overview/data-and-trends/statistics (Accessed May 21, 2025). HIV.gov. Viral suppression and undetectable viral load. 2025. Available from: https://www.hiv.gov/hiv-basics/staying-in-hiv-care/hiv-treatment/viral-suppression (Accessed July 18, 2025). HIV.gov. Who is at risk for HIV. 2025. Available from: https://www.hiv.gov/hiv-basics/overview/about-hiv-and-aids/who-is-at-risk-for-hiv (Accessed June 25, 2025). Johns Hopkins Bloomberg School of Public Health. What to know about PrEP. 2025. Available from: https://publichealth.jhu.edu/2025/who-needs-prep-for-hiv-prevention (Accessed June 25, 2025). Kamis KF et al. Open Forum Infect Dis 2019;6:ofz310. KFF. HIV testing in the United States. 2024. Available from: https://www.kff.org/hiv-aids/hiv-testing-in-the-united-states/ting in the United States | KFF (Accessed August 26, 2025). NIH. HIV and sexually transmitted infections (STIs). 2021. Available from: https://hivinfo.nih.gov/understanding-hiv/fact-sheets/hiv-and-sexually-transmitted-infections-stis (Accessed June 25, 2025). Ramchandani MS et al. Curr HIV/AIDS Rep 2019;16:244–56. Saag MS et al. JAMA 2018;320:379–96. Sweeney P et al. J Acquir Immune Defic Syndr 2019;82(Suppl 1):S1–5. The White House. National HIV/AIDS strategy for the United States 2022–2025. 2021. Available from: https://files.hiv.gov/s3fs-public/NHAS-2022-2025.pdf (Accessed June 25, 2025). UNAIDS.org. Recommended 2030 targets for HIV. 2025. Available from: https://www.unaids.org/en/recommended-2030-targets-for-hiv (Accessed August 26, 2025). United States Census Bureau. National population by characteristics: 2020-2024. 2024. Available from: https://www.census.gov/data/tables/time-series/demo/popest/2020s-national-detail.html (Accessed June 25, 2025). United States Census Bureau. United States Population Growth by Region. 2025. Available from: https://www.census.gov/popclock/ (Accessed June 25, 2025). Yumori C et al. Sex Transm Dis 2021;48:32–6.

Overview: In this episode, Dr Melissa Jones and Dr Christian Ramers discuss the importance of pan-viral screening for HIV and hepatitis. They emphasize the need for integrated testing and prevention strategies and the current barriers to implementation. The views expressed are those of the panelist(s) and not necessarily Gilead Sciences, Inc. The information provided in this podcast is not intended to be and should not be understood to provide medical advice. Listeners should note that our discussions in this episode are relevant to the USA only and may not be appropriate for other regions. This episode was recorded in August 2025 and the content reflects the information available at that time. Guest: Christian B Ramers, MD, MPH, FIDSA, AAHIVS; Melissa Jones, DNP, APRN-BC   For more information, please visit: https://www.pri-med.com/clinical-resources/curriculum/hiv-in-focus  References AASLD/IDSA. HCV guidance: recommendations for testing, managing, and treating hepatitis C. 2025. 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Overview: In this episode, Dr Joel Gallant gives a history of antiretroviral therapy and HIV drug resistance, drawing on his personal and professional experience beginning in the early 1980s. The views expressed are those of the panelist and not necessarily Gilead Sciences, Inc. The information provided in this podcast is not intended to be and should not be understood to provide medical advice. Listeners should note that our discussions in this episode are relevant to the USA only and may not be appropriate for other regions. This episode was recorded in August 2023 and the content reflects the information available at that time. Guest: Joel Gallant, MD, MPH    For more information, please visit: https://www.pri-med.com/clinical-resources/curriculum/hiv-in-focus    References AIDSVu.org. New HIV diagnoses. 2023. 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Send us a textGood morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we're diving into a series of groundbreaking developments that are reshaping the landscape of drug development and patient care. These stories highlight the dynamic nature of the pharmaceutical and biotechnology industries, where scientific advancements and regulatory changes are driving significant shifts.We begin with a crucial milestone in oncology treatment. The FDA has granted approval to Johnson & Johnson's Darzalex Faspro for patients with high-risk smoldering multiple myeloma. This approval is particularly significant as it provides a new therapeutic pathway for individuals with this precursor condition to active multiple myeloma, which previously had few treatment options. The drug works by targeting CD38 proteins on myeloma cells, representing a leap forward in monoclonal antibody treatments for cancer. This decision underscores the FDA's ongoing commitment to expanding treatment options for conditions with high unmet needs, potentially setting a precedent for future approvals in early-stage malignancies.Meanwhile, Gilead Sciences encountered challenges with its oncology pipeline as Trodelvy failed to meet its primary endpoint in a Phase 3 trial for first-line HR+/HER2-negative metastatic breast cancer. This outcome highlights the complexities of oncology drug development, despite previous successes in other indications. Such setbacks remind us of the inherent risks involved in bringing innovative therapies to market.In contrast, Akeso has announced positive data for ivonescimab, a PD-(L)1xVEGF bispecific antibody. The drug demonstrated significant overall survival benefits in patients with previously treated EGFR-mutated non-small cell lung cancer. This advancement underscores the therapeutic potential of bispecific antibodies in cancer immunotherapy, which continue to gain traction as they target multiple pathways involved in tumor growth and immune evasion.Regulatory incentives have also been making waves. The FDA's rollout of the second round of "national priority" voucher winners aims to accelerate drug development timelines, particularly in critical areas such as obesity. Companies like Lilly and Novo Nordisk have been recognized for their efforts, highlighting a broader strategy to bring transformative therapies to market more swiftly.On the corporate front, Bayer's proposed private equity buyout fell through due to insufficient shareholder support, reflecting ongoing financial volatility and strategic recalibrations within biotech firms. Meanwhile, CMS's introduction of a new Medicaid pricing model aims to implement "most-favored nation" pricing strategies to control drug costs, signaling potential shifts in how pharmaceutical companies approach pricing negotiations and reimbursement strategies.Technological advancements are also at the forefront of innovation. Eli Lilly has expanded its AI-driven drug discovery partnership with XtalPi, focusing on antibody development. This collaboration exemplifies how AI is increasingly being integrated into pharmaceutical research to enhance drug discovery processes.Furthermore, China's decision to lift its ban on Illumina's DNA sequencers is expected to facilitate greater access to advanced genomic technologies within the region, fostering innovation in precision medicine.Leadership changes continue to shape industry dynamics. For instance, Recursion Pharmaceuticals is undergoing executive restructuring to better align with evolving market needs and innovation strategies. These changes are crucial for maintaining competitiveness and fostering an environment conducive to scientific breakthroughs.The industry is also witnessing strategic realignmenSupport the show

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we're diving into a series of fascinating advancements and strategic movements that are shaping the landscape of drug development and patient care.Starting with a significant milestone in precision oncology, China has approved its first EGFR-targeted antibody-drug conjugate. This approval marks a pivotal moment in the industry's shift towards targeted therapies, which promise more precise treatment options with potentially fewer side effects than traditional chemotherapy. Targeted therapies are at the forefront of personalized medicine, where treatments are tailored to individual genetic profiles, offering hope for more effective cancer care.In the realm of HIV prevention, Gilead Sciences has reported impressive sales for its new long-acting pre-exposure prophylaxis medication, Yetztugo. Since its launch in June 2025, Yetztugo has generated $54 million in U.S. sales, underscoring the demand for long-term HIV prevention solutions. This development is part of Gilead's broader strategy to strengthen its HIV franchise as it advances its pipeline with promising candidates like GS-3242 alongside lenacapavir. The aim is to develop treatments that require less frequent dosing, which could significantly improve patient adherence and outcomes. Despite challenges within its HIV portfolio and declining Veklury sales, Gilead Sciences is actively seeking growth opportunities through strategic partnerships and pipeline advancements—an essential approach for navigating patent cliffs while sustaining long-term growth.On the financial front, AbbVie has increased its revenue forecast by $400 million to a staggering $60.9 billion, driven by robust sales from its immunology drugs Skyrizi and Rinvoq. These treatments address chronic inflammatory conditions like psoriasis and rheumatoid arthritis, reflecting AbbVie's strong positioning in this therapeutic area despite competitive pressures. AbbVie continues to report strong earnings from Skyrizi and Rinvoq, reinforcing its dominance in the immunology market and highlighting the profitable nature of successful biologics in treating chronic inflammatory diseases.Biogen continues to bolster its multiple sclerosis franchise by focusing on both legacy treatments and new product launches. This strategy highlights the importance of balancing innovation with lifecycle management to maintain market strength against generic competition—a common challenge in the industry.Meanwhile, the American Academy of Pediatrics has taken a cautious stance by not endorsing leucovorin for autism treatment due to insufficient evidence. This decision emphasizes the critical need for rigorous, evidence-based practices in developing clinical guidelines for complex disorders like autism.Internationally, CSL Seqirus has partnered with Saudi Arabia to supply cell-based influenza vaccines and support local production capabilities. This move aligns with global efforts to enhance pandemic preparedness and healthcare resilience through local manufacturing initiatives.The volatile nature of the biotech sector is evident with reports of 16 companies ceasing operations in 2025 due to high R&D costs and regulatory challenges. Despite these closures, such volatility opens doors for new innovations that could address unmet medical needs.Turning our attention to obesity treatment, Eli Lilly stands at a crucial juncture with its novel obesity medication, orforglipron. The company aims to make this weight loss pill accessible while maintaining financial viability for future R&D—a balancing act faced by many pharmaceutical companies as they strive to deliver affordable yet innovative treatments amid growing global health concerns. However, not all R&D efforts reach fruition. Eli Lilly has decided to discontinue its mid-stage program Support the show

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE/AAPA information, and to apply for credit, please visit us at PeerView.com/QHH865. CME/NCPD/CPE/AAPA credit will be available until October 21, 2026.Advancing PBC Care Through Timely Referral and Treatment: From Diagnosis to Long-Term Management In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis program has been supported by an independent educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE/AAPA information, and to apply for credit, please visit us at PeerView.com/QHH865. CME/NCPD/CPE/AAPA credit will be available until October 21, 2026.Advancing PBC Care Through Timely Referral and Treatment: From Diagnosis to Long-Term Management In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis program has been supported by an independent educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE/AAPA information, and to apply for credit, please visit us at PeerView.com/QHH865. CME/NCPD/CPE/AAPA credit will be available until October 21, 2026.Advancing PBC Care Through Timely Referral and Treatment: From Diagnosis to Long-Term Management In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis program has been supported by an independent educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE/AAPA information, and to apply for credit, please visit us at PeerView.com/QHH865. CME/NCPD/CPE/AAPA credit will be available until October 21, 2026.Advancing PBC Care Through Timely Referral and Treatment: From Diagnosis to Long-Term Management In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis program has been supported by an independent educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE/AAPA information, and to apply for credit, please visit us at PeerView.com/QHH865. CME/NCPD/CPE/AAPA credit will be available until October 21, 2026.Advancing PBC Care Through Timely Referral and Treatment: From Diagnosis to Long-Term Management In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis program has been supported by an independent educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE/AAPA information, and to apply for credit, please visit us at PeerView.com/QHH865. CME/NCPD/CPE/AAPA credit will be available until October 21, 2026.Advancing PBC Care Through Timely Referral and Treatment: From Diagnosis to Long-Term Management In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis program has been supported by an independent educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE/AAPA information, and to apply for credit, please visit us at PeerView.com/QHH865. CME/NCPD/CPE/AAPA credit will be available until October 21, 2026.Advancing PBC Care Through Timely Referral and Treatment: From Diagnosis to Long-Term Management In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis program has been supported by an independent educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/NCPD/CPE/AAPA information, and to apply for credit, please visit us at PeerView.com/QHH865. CME/NCPD/CPE/AAPA credit will be available until October 21, 2026.Advancing PBC Care Through Timely Referral and Treatment: From Diagnosis to Long-Term Management In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis program has been supported by an independent educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

Dr. Hope Rugo and Dr. Giuseppe Curigliano discuss recent developments in the field of bispecific antibodies for hematologic and solid tumors, including strategies to optimize the design and delivery of the immunotherapy. TRANSCRIPT Dr. Hope Rugo: 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 am your host, Dr. Hope Rugo. I am the director of the Women's Cancers Program and division chief of breast medical oncology at the City of Hope Cancer Center. I am also the editor-in-chief of the Educational Book. Bispecific antibodies represent an innovative and advanced therapeutic platform in hematologic and solid tumors. And today, I am delighted to be joined by Dr. Giuseppe Curigliano to discuss the current landscape of bispecific antibodies and their potential to reshape the future of precision oncology. Dr. Curigliano was the last author of an ASCO Educational Book piece for 2025 titled, "Bispecific Antibodies in Hematologic and Solid Tumors: Current Landscape and Therapeutic Advances." Dr. Curigliano is a breast medical oncologist and the director of the Early Drug Development Division and chair of the Experimental Therapeutics Program at the European Institute of Oncology in Milan. He is also a full professor of medical oncology at the University of Milan. You can find our disclosures in the transcript of this episode. Dr. Curigliano, Giuseppe, welcome and thanks for being here. Dr. Giuseppe Curigliano: Thanks a lot for the invitation. Dr. Hope Rugo: Giuseppe, I would like to first ask you to provide some context for our listeners on how these novel therapeutics work. And then perhaps you could tell us about recent developments in the field of bispecific antibodies for oncology. We are at a time when antibody-drug conjugates (ADCs) are all the rage and, trying to improve on the targeting of specific antigens, proteins, receptors in the field of oncology is certainly a hot and emerging topic. Dr. Giuseppe Curigliano: So, thanks a lot. I believe really it was very challenging to try to summarize all the bispecific antibodies that are under development in multiple solid tumors. So, the first thing that I would like to highlight is the context and the mechanism of action of bispecific antibodies. Bispecific antibodies represent a groundbreaking advancement in cancer immunotherapy, because these engineered molecules have the unique ability to target and simultaneously bind to two distinct antigens. That is why we call them bispecific. So typically, one antigen is expressed on the tumor cell and the other one is expressed on the immune effectors, like T-cell or natural killer cells. So this dual targeting mechanism offers several key advantages over conventional monoclonal antibodies because you can target at the same time the tumor antigen, downregulating the pathway of proliferation, and you can activate the immune system. So the primary mechanism through which bispecific antibodies exert their therapeutic effects are: First, T-cell redirecting. I mean, many bispecific antibodies are designed to engage tumor-associated antigens like epidermal growth factor receptor, HER2, on the cancer cell and a costimulatory molecule on the surface of T-cell. A typical target antigen on T-cell is CD3. So what does it mean? That you activate the immune system, immune cells will reach the tumor bed, and you have a dual effect. One is downregulating cell proliferation, the other one is activation of the immune system. This is really important in hematological malignancies, where we have a lot of bispecifics already approved, like acute lymphoblastic leukemia or non-Hodgkin lymphoma.  The second, in fact, is the engagement of the tumor microenvironment. So, if you engage immune effector cells like NK cells or macrophages, usually the bispecific antibodies can exploit the immune system's ability to recognize and kill the immune cells, even if there is a lack of optimal antigen presentation.  And finally, the last mechanism of action, this may have a role in the future, maybe in the early cancer setting, is overcoming immune evasion. So bispecific antibodies can overcome some of the immune evasion mechanisms that we see in cancer. For example, bispecific antibodies can target immune checkpoint receptors, like PD-L1 and CTLA-4. Actually, there is a bispecific under development in breast cancer that has a dual targeting on vascular endothelial growth factor receptor and on PD-L1. So you have a dual effect at the same time. So, what is really important, as a comment, is we need to focus first on the optimal format of the bispecific, the optimal half-life, the stability, because of course even if they are very efficient in inducing a response, they may give also a lot of toxicities. So in clinical trials already, we have several bispecifics approved. In solid tumors, very few, specifically amivantamab for non-small cell lung cancer, but we have a pipeline of almost 40 to 50 bispecifics under development in multiple solid tumors, and some of them are in the context of prospective randomized trials. Dr. Hope Rugo: So this is really a fascinating area and it's really exciting to see the expansion of the different targets for bispecific antibodies. One area that has intrigued me also is that some of the bispecifics actually will target different parts of the same receptor or the same protein, but presumably those will be used as a different strategy. It's interesting because we have seen that, for example, in targeting HER2. Dr. Giuseppe Curigliano: Oh, yes, of course. You may consider some bispecifics like margetuximab, I suppose, in which you can target specifically two different epitopes of the same antigen. This is really an example of how a bispecific can potentially be more active and downregulating, let us say, a pathway, by targeting two different domains of a specific target antigen. This is an important point.  Of course, not all the bispecifics work this way, because some of the target antigen may dimerize, and so you have a family of target antigen; an example is epidermal growth factor receptor, in which you have HER1, HER2, HER3, and HER4. So some of them can inhibit the dimerization between one target antigen and the other one, in order to exert a more antiproliferative effect. But to be honest, the new generation of them are more targeting two different antigens, one on the tumor and one on the microenvironment, because according to the clinical data, this is a more efficient way to reduce proliferation and to activate the immune system. Dr. Hope Rugo: Really interesting, and I think it brings us to the next topic, which is really where bispecific antibodies have already shown success, and that is in hematologic malignancies where we have seen very interesting efficacy and these are being used in the clinic already. But the expansion of bispecific antibodies into solid tumors faces some key challenges. It's interesting because the challenges come in different shapes and forms. Tell us about some of those challenges and strategies to optimize bispecific antibody design, delivery, patient selection, and how we are going to use these agents in the right kind of clinical trials. Dr. Giuseppe Curigliano: This is really an excellent question because despite bispecific antibodies having shown a remarkable efficacy in hematological malignancies, their application in solid tumors may have some challenges. The first one is tumor heterogeneity. In hematological malignancy, you have a clear oncogene addiction. Let us say that 90% of the cells may express the same antigen. In solid tumors, it is not the same. Tumor heterogeneity is a typical characteristic of solid tumors, and you have high heterogeneity at the genetic, molecular, and phenotypic levels. So tumor cells can differ significantly from one another, even if within the same tumor. And this heterogeneity sometimes makes it difficult to identify a single target antigen that is universally expressed in an hematological malignancy. So furthermore, sometimes the antigen expressed on a tumor cell can be also present on the normal tissue. And so you may have a cross-targeting. So let's say, if you have a bispecific against epidermal growth factor receptor, this will target the tumor but will target also the skin with a lot of toxicity. The second challenge is the tumor microenvironment. The solid tumor microenvironment is really complex and often immunosuppressive. It is characterized by the presence of immunosuppressor cells like the T regulators, myeloid derived suppressor cells, and of course the extracellular matrix. All these factors hinder immune cell infiltration and also may reduce dramatically the effectiveness of bispecific antibodies. And as you know, there is also an hypoxic condition in the tumor. The other challenge is related to the poor tumor penetration. As you know also with antibody-drug conjugate, only 1 to 3% of the drug will arrive in the tumor bed. Unlike hematological malignancies where tumor cells are dispersed in the blood and easily accessible, the solid tumors have a lot of barriers, and so it means that tumor penetration can be very low. Finally, the vascularity also of the tumor can be different across solid tumors. That is why some bispecifics have a vascular endothelial growth factor receptor or vascular endothelial growth factor as a target. Of course, what do we have to do to overcome these challenges? First, we have to select the optimal antigen. So knowing very well the biology of cancer and the tumor-associated antigens can really select a subgroup of epitopes that are specifically overexpressed in cancer cells. And so we need to design bispecifics according to the tumor type. Second, optimize the antibody format. So there are numerous bispecific antibody formats. We can consider the dual variable domain immunoglobulin, we specified this in our paper. The single chain variable fragments, so FC variable fragments, and the diabodies that can enhance both binding affinity and stability. And finally, the last point, combination therapies. Because bispecific antibodies targeting immune checkpoint, we have many targeting PD-1 or PD-L1 or CTLA-4, combined eventually with other immune checkpoint inhibitors. And so you may have more immunostimulating effect. Dr. Hope Rugo: This is a fascinating field and it is certainly going to go far in the treatment of solid tumors. You know, I think there is some competition with what we have now for antibody-drug conjugates. Do you see that bispecifics will eventually become bispecific ADCs? Are we going to combine these bispecific antibodies with ADCs, with chemotherapy? What is the best combination strategy do you think looking forward? Dr. Giuseppe Curigliano: So, yes, we have a bispecific ADC. We have actually some bispecifics that are conjugated with a payload of chemotherapy. Some others are conjugated with immunoactivation agents like IL-2. One of the most effective strategies for enhancing bispecific activity is the combination therapy. So which type of combination can we do? First, bispecific antibodies plus checkpoint inhibitors. If you combine a bispecific with an immune checkpoint, like anti-PD-1, anti-PD-L1, or anti-CTLA-4, you have more activity because you have activation of T-cells, reduction of immunosuppressive effect, and of course, the capability of this bispecific to potentiate the activity of the immune checkpoint inhibitor. So, in my opinion, in a non-small cell lung cancer with an expression of PD-L1 more than 50%, if you give pembrolizumab plus a bispecific targeting PD-L1, you can really improve both response rate and median progression-free survival.  Another combination is chemotherapy plus bispecific antibodies. Combining chemotherapy with bispecific can enhance the cytotoxic effect because chemotherapy induces immunogenic cell death, and then you boost with a bispecific in order to activate the immune system. Bispecific and CAR T-cells, until now, we believe that these are in competition, but this is not correct. Because CAR T-cells are designed to deliver an activation of the immune system with the same lymphocytes engineered of the patients, with a long-term effect. So I really do not believe that bispecifics are in competition with CAR T-cells because when you have a complete remission induced by CAR T-cell, the effect of this complete remission can last for years. The activity of a bispecific is a little bit different. So there are some studies actually combining CAR T-cells with bispecifics. For example, bispecific antibodies can direct CAR T-cells in the tumor microenvironment, improving their specificity and enhancing their therapeutic effect.  And finally, monoclonal antibody plus bispecific is another next generation activity. Because if you use bispecific antibodies in combination with existing monoclonal antibodies like anti-HER2, you can potentially increase the immune response and enhance tumor cell targeting. In hematological malignancies, this has been already demonstrated and this approach has been particularly effective. Dr. Hope Rugo: That's just so fascinating, the whole idea that we have these monoclonal antibodies and now we are going to add them to bispecifics that we could maybe attach on different toxins to try and improve this, or even give them with different approaches. I suppose giving an ADC with a bispecific would sort of be similar to that idea of giving a monoclonal antibody with the bispecific. So it is certainly intriguing. We also will need to understand the toxicity and cost overall and how we are going to use these, the duration of treatment, the assessment of biomarkers. There are just so many different aspects that still need to be explored.  And then with that idea, can you look ahead five or ten years from now, and tell us how you think bispecific antibodies will shape our next generation cancer therapies, how they will be incorporated into precision oncology, and the new combinations and approaches as we move forward that will help us tailor treatment for patients both with solid tumors and hematologic malignancies? Are we going to be giving these in early-stage disease in solid tumors? So far, the studies are primarily focusing on the metastatic setting, but obviously one of the goals when we have successful treatments is to move them into the early stage setting as quickly as possible. Dr. Giuseppe Curigliano: Let us try to look ahead five years rather than ten years, to be more realistic. So, personally I believe some bispecifics can potentially replace current approaches in specifically T-cell selected population. As we gather more data from ongoing clinical trials and we adopt a deeper understanding of the tumor immuno microenvironment, of course we may have potentially new achievement. A few days ago, we heard that bispecifics in triple negative breast cancer targeting VEGF and PD-L1 demonstrated an improvement in median progression-free survival.  So, how to improve and to impact on clinical practice both in the metastatic and in the early breast cancer setting or solid tumor setting? First, personalized antigen selection. So we need to have the ability to tailor bispecific antibody therapy to the unique tumor profile of individual patients. So the more we understand the biology of cancers, the more we will be able to better target. Second, bispecific antibodies should be combined. I can see in the future a potential trial in which you combine a bispecific anti-PD-L1 and VEGF with immune checkpoint inhibitor selected also to the level of expression of PD-L1, because integration of antibody bispecific with a range of immunotherapies, and this cannot be only immune checkpoint inhibitors, but can be CAR T-cells, oncolytic viruses, also targeted therapy, will likely be a dominant theme in the coming years. This combination will be based on the specific molecular and immuno feature of the cancer of the patient.  Then we need an enhanced delivery system. This is really important because you know now we have a next generation antibody. An example are the bicyclic. So you use FC fragment that are very short, with a low molecular weight, and this short fragment can be bispecific, so can target at the same time a target antigen and improving the immune system. And so the development of this novel delivery system, including also nanoparticles or engineered viral vectors, can enhance the penetration in the tumor bed and the bioavailability of bispecific antibodies. Importantly, we need to reduce toxicity. Until now, bispecifics are very toxic. So the more we are efficient in delivering in the tumor bed, the more we will reduce the risk of toxicity. So it will be mandatory to reduce off-target effects and to minimize toxicity.  And finally, the expansion in new indication. So I really believe you raised an excellent point. We need to design studies in the neoadjuvant setting in order to better understand with multiple biopsies which is the effect on the tumor microenvironment and the tumor itself, and to generate hypotheses for potential trials or in the neoadjuvant setting or in those patients with residual disease.  So, in my opinion, as we refine design, optimize patient selection, and explore new combination, in the future we will have more opportunity to integrate bispecifics in the standard of care. Dr. Hope Rugo: I think it is particularly helpful to hear what we are going to be looking for as we move forward to try and improve efficacy and reduce toxicity. And the ability to engineer these new antibodies and to more specifically target the right proteins and immune effectors is going to be critical, of course, moving forward, as well as individualizing therapy based on a specific tumor biology.  Hearing your insights has been great, and it really has opened up a whole area of insight into the field of bispecifics, together with your excellent contribution to the ASCO Educational Book. Thank you so much for sharing your thoughts and background, as well as what we might see in the future on this podcast today. Dr. Giuseppe Curigliano: Thank you very much for the invitation and for this excellent interview. Dr. Hope Rugo: And thanks to our listeners for joining us today. You will find a link to the Ed Book article we discussed today in the transcript of this episode. It is also, of course, on the ASCO website, as well as on PubMed. Please join us again next month on By the Book for more insightful views on the key issues and innovations that are shaping modern oncology. 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. Hope Rugo  @hope.rugo  Dr. Giuseppe Curigliano @curijoey Follow ASCO on social media:       @ASCO on X (formerly Twitter)       ASCO on Bluesky      ASCO on Facebook       ASCO on LinkedIn       Disclosures:      Dr. Hope Rugo:   Honoraria: Mylan/Viatris, Chugai Pharma  Consulting/Advisory Role: Napo Pharmaceuticals, Sanofi, Bristol Myer  Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Merck, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Hoffman La-Roche AG/Genentech, In., Stemline Therapeutics, Ambryx  Dr. Giuseppe Curigliano: Leadership: European Society for Medical Oncology, European Society of Breast Cancer Specialists, ESMO Open, European Society for Medical Oncology Honoraria: Ellipses Pharma Consulting or Advisory Role: Roche/Genentech, Pfizer, Novartis, Lilly, Foundation Medicine, Bristol-Myers Squibb, Samsung, AstraZeneca, Daiichi-Sankyo, Boerigher, GSK, Seattle Genetics, Guardant Health, Veracyte, Celcuity, Hengrui Therapeutics, Menarini, Merck, Exact Sciences, Blueprint Medicines, Gilead Sciences Speakers' Bureau: Roche/Genentech, Novartis, Pfizer, Lilly, Foundation Medicine, Samsung, Daiichi Sankyo, Seagen, Menarini, Gilead Sciences, Exact Sciences Research Funding: Merck Travel, Accommodations, Expenses: Roche/Genentech, Pfizer, Daiichi Sankyo, AstraZeneca      

Dr. Monty Pal and Dr. Matteo Lambertini discuss a compelling global study on the clinical behavior of breast cancer in young BRCA1 and BRCA2 carriers, the association of pre-diagnostic awareness of BRCA status with prognosis, and the importance of identifying healthy people who are at risk of carrying the BRCA1/2 pathogenic variants. TRANSCRIPT Dr. Monty Pal: Well, hello everyone, 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 medical oncology at the City of Hope Comprehensive Cancer Center in Los Angeles. Now, when we think about genetic testing, whether for patients diagnosed with breast cancer or for other family members of them, it seems to be widely underutilized. Today, we're going to be discussing a recently published study in the Journal of Clinical Oncology that reported on the clinical behavior of breast cancer and specifically young BRCA1 and BRCA2 carriers, and the association of pre-diagnostic awareness of BRCA status with prognosis. I thought this was just a fascinating piece, and I honestly couldn't wait to have this conversation. It's a really compelling paper that highlights the importance of identifying healthy people who are at risk of carrying the BRCA1/2 pathogenic variants, and really the need for genetic counseling and testing to inform people about early detection that could lead to a better prognosis. I'm really delighted to welcome the study's lead author, Dr. Matteo Lambertini. He really needs no introduction. He's very well known in the breast cancer world for his amazing contributions to fertility in the context of breast cancer, to pregnancy in the context of breast cancer, and genetic testing. He's an associate professor at the University of Genova, and a breast cancer medical oncologist at the San Martino Polyclinic Hospital in Genova, Italy.  Dr. Lambertini, thank you so much for joining us today. Dr. Matteo Lambertini: Thank you very much, Dr. Pal. It's a great pleasure. Dr. Monty Pal: Oh, thanks. And just FYI, if you're listening in and you want to hear our disclosures, they're all listed at the transcript of this podcast.  So, I poured through this paper [Clinical Behavior of Breast Cancer in Young BRCA Carriers and Prediagnostic Awareness of Germline BRCA Status] yesterday, Dr. Lambertini, and first of all, congratulations on this study. This was a huge international multicenter effort, 4,752 patients. How did you pool all these patients with young breast cancer? Dr. Matteo Lambertini: Thanks a lot for the question. Yes, this was an effort made by several centers all over the world. The main idea behind the creation of this network that we have named as BRCA BCY Collaboration, was to get as many data as possible in a sort of niche patient population in the breast cancer field, meaning women diagnosed with breast cancer at the age of 40 years or younger, and all of them being BRCA carriers. We know that around, in the Western world, around 5% of breast cancer cases are being diagnosed under the age of 40 years, and among them around 10-15% are BRCA carriers. So, I would say it's a relatively rare patient population where we did not have a lot of evidence to support our choices in terms of counseling on treatment, prevention, and oncofertility as well. That was the idea behind the creation of this network that includes many centers. Dr. Monty Pal: Yeah. You know, what's so interesting about this is that you sort of draw this line between patients who have BRCA testing at the time of diagnosis and then BRCA testing earlier in their course and then leading to a diagnosis perhaps. And I think that's where really sort of the dichotomy in outcome sits. Can you maybe elaborate on this and tell us about timing of genetic testing in this study and what that meant ultimately in terms of prognosis? Dr. Matteo Lambertini: In this specific analysis from this large network, including almost 5,000 women with breast cancer diagnosed at the age of 40 years or younger and being a BRCA carrier, we looked specifically into the timing of genetic testing because this is a retrospective study and the criteria for inclusion are those that I have just mentioned, so diagnosis at a young age plus carrying germline BRCA pathogenic or likely pathogenic variant. In this analysis, we have looked into the time the patient has got the genetic testing and particular we focused on two populations: those that were diagnosed, knowing already to be a BRCA carrier, and those that got tested after being diagnosed with breast cancer. And the main findings from this analysis have been that knowing to be a BRCA carrier was associated with a lower stage at the time of diagnosis, meaning more T1 tumors, so a tumor less than 2 cm, more node-negative disease, and this translated into less aggressive treatment, so less often axillary dissection, less often use of chemotherapy and anthracycline-based chemotherapy. And even more importantly, we have seen a better overall survival for those patients that were diagnosed already knowing to be BRCA carriers as compared to those tested after breast cancer diagnosis. These results after adjusting for all the confounding, stage, treatment and so on, there was not significant anymore, meaning that it's not the timing of test per se that is probably leading to a better survival, but it is the fact that knowing to be a BRCA carrier would likely translate into having access to all the preventive measures that we have in this setting and this will translate into an overall survival benefit, so in terms of saving more lives in young BRCA carriers. Dr. Monty Pal: I think it's such an important point, and it's one that I think might sound implicit, right, but it needs to be proven, I think, through a study like this. You know, the fact that finding this early, identifying the mutation, doing enhanced screening, and so forth, is really going to lead to superior clinical outcomes. One of the things that I think many people puzzle over, including myself, is what to do? I personally occasionally will see BRCA altered patients in the context of prostate cancer. But that's a very different population of individuals, right? Typically older men. In young females with BRCA mutation, I guess there's a specific set of considerations around reproductive health. You'd already highlighted preventive strategies, but what sorts of things should we be talking about in the clinics once a patient's diagnosed and once perhaps their breast cancer diagnosis is established? Dr. Matteo Lambertini: Yes, exactly. Knowing to be a BRCA carrier has a lot of implications from prevention to treatment to survivorship issues including reproductive counseling. And this is important not only for the patient that has been diagnosed with breast cancer but also for all the family members that will get tested and maybe identify with this sort of genetic alteration before diagnosis of cancer. Why this is important is because we have access to very effective preventive measures, a few examples: MRI screening, which starts at a very young age and normally young women don't have an effective screening strategy outside the BRCA field. Also, primary preventive measures, for example, risk-reducing surgery. These women are known to have a high risk of breast cancer and high risk of ovarian cancer. So the guidelines are suggesting to undergo risk-reducing salpingo-oophorectomy at a young age, so 35 to 40 years in BRCA1 carrier, 40 to 45 years in BRCA2 carrier. And also risk-reducing mastectomy should be discussed because it is a very effective way to prevent the occurrence of breast cancer. And in some situations, including the setting that we are talking about, so young women with breast cancer, BRCA carrier, also risk-reducing mastectomy has shown to improve overall survival.  On the other side, once diagnosed with breast cancer, nowadays knowing to be or not a BRCA carrier can make a difference in terms of treatment. We have PARP inhibitors in the early setting, in the adjuvant setting as well as in the metastatic setting. And in terms of survivorship implication, one of the critical aspects for young women is the oncofertility care which is even more complicated when we talk about BRCA carriers that are women candidates for gynecological surgery at a very young age. So this sort of counseling is even more complicated. Dr. Monty Pal: One of the other things, and this is subtle in your paper and I hope you don't mind me bringing it up, is the difference between BRCA1 and BRCA2. It really got me thinking about that because there are differences in phenotype and manifestation. Do you mind just expanding on that a little bit for the audience because I think that's a really important reminder that you brought up in the discussion? Dr. Matteo Lambertini: The difference between BRCA1 and BRCA2 carriers has been known that there are different phenotypes of breast cancer that are more often diagnosed in these two different populations. Normally BRCA1 carriers have a higher likelihood to develop a triple negative breast cancer as compared to BRCA2 carriers, more likely to develop a hormone receptor-positive HER2-negative disease. In this study, again, a specific population of young women with breast cancer, we have seen the same findings, mostly triple negative disease in BRCA1 carrier, mostly luminal-like disease in BRCA2 carrier. But what's novel or interesting from this study is to look also at the age at the time of diagnosis of this disease. And particularly in BRCA1 carriers, we should be sort of more careful about diagnosis of breast cancer and also other primary tumors including ovarian cancer because the risk of developing these malignancies is higher even at a younger age as compared to BRCA2 carriers. And this has implications also in the primary and secondary prevention that we were talking about earlier. Dr. Monty Pal: Oh, interesting. I guess the fundamental question then from your paper becomes, how do we get at the right patients for screening for BRCA1 and BRCA2? And I realize our audience here is largely oncologists who are going to be listening to this podcast, oncology providers, MDs, nurses, etc. But maybe speak for a moment to the general practitioner. Are there things that, for instance, a general practitioner should be looking for to say, “Wait a minute, this patient's high risk, we should consider BRCA1, BRCA2 testing or germline screening”? Dr. Matteo Lambertini: Yes, it's a very important question for the breast cancer community. After the updated ASCO guideline, the counseling is way easier because right now the age cutoff goes up to 65 years, meaning that all the patients diagnosed with breast cancer below the age of 65 years should be tested these days. And then above the age of 65, there are different criteria like triple-negative disease or family history. From a general practitioner standpoint, it's of course a bit more difficult, but knowing particularly the family history of the person that they have in front will be crucial to know if there are cases of breast cancer diagnosed at a young age, maybe triple-negative cases, knowing cases of ovarian cancer in first-degree relatives or pancreatic cancer in first-degree relatives, and of course cases of prostate cancer as well. So, I would say probably mostly the family side will be important from a general practitioner perspective.  From an oncology one, the other point that I think is important to stress also based on the data that we have shown in this publication is that having a case of breast cancer known to carry a BRCA pathogenic or likely pathogenic variant. It means that all the people around this case should get tested and if found to be BRCA carrier and healthy carrier, these people should also undergo the primary and secondary prevention strategies because this is very critical also to improve their outcomes and try to avoid the developing of breast or ovarian cancer, but also in the case of diagnosis of this disease, a diagnosis at an earlier stage, as we have seen in this paper. Dr. Monty Pal: Brilliant. I'm going to diverge from our list of questions here and close by asking a question that I have at the top of my mind. You're very young. I know our podcast listeners can't see you, but you're very, very young. Dr. Matteo Lambertini: Thank you. Thank you for that. Not so young but yeah. Dr. Monty Pal: You have nearly 300 papers. Your H-index is 67. You've already made these seminal contributions, as I outlined it from the outset, regarding fertility, regarding use of GnRH analogs, regarding pregnancy and breast cancer. What are you studying now? What are you really excited about right now that you're doing that you think might potentially be practice changing? Give us a little teaser. Dr. Matteo Lambertini: Yeah. Thanks a lot, Dr. Pal. Receiving this compliment from you is fantastic. So, thanks a lot for that. From my side, in terms of my research, I've been interested in the field of breast cancer in young women since the start of my training. I've had very good mentors from Italy, from Europe, from the U.S. I'm still interested in this field, so I think we still have a lot to learn to try to improve the care of young women with breast cancer. For example, the oncofertility care, which is something I worked a lot over the past years. Now with all the new treatment options, there's a sort of new chapter of oncofertility counseling. So, what's the impact of immunotherapy? What's the impact of the new targeted agents?  More on the genetic aspects, now we know that there's not only BRCA1 or BRCA2. There are a lot of other different genes that may increase the risk of breast cancer and other malignancies. And also for these genes, we really don't have a lot of evidence to counsel women on prognosis, treatment, prevention strategy. So we need to learn way more for this special patient population that are quite rare, and so we really need a multicenter academic effort to try to give some evidence in this field. Dr. Monty Pal: Yeah. It's tough because these are rare circumstances, but, you know, I think that you've done really well to sort of define some collective experiences that I think really define therapy. I mean, I just remember when I was in training 25 years ago, just reading through textbooks where all the experience around breast cancer and pregnancy was really just very sort of anecdotal almost, you know? And so it's great to see that the state of the science has moved forward.  Well, gosh, I really enjoyed our conversation today. I think your study really reminds us how powerful genetic information is in terms of improving outcomes. And, you know, hopefully this will lead some individuals to perhaps test more broadly in appropriate settings. So, thank you so much, Matteo, for joining us today with your fantastic insights on the ASCO Daily News Podcast. Dr. Matteo Lambertini: Thank you very much, Dr. Pal. It's a real pleasure. Dr. Monty Pal: And thanks to our listeners too. You'll find a link to Dr. Lambertini's study in the transcript of this episode. Finally, if you value the insights that you heard today on the ASCO Daily News Podcast, please rate, review, and subscribe wherever you get your podcasts. Thanks a ton. 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. Sumanta (Monty) Pal  @montypal  Dr. Matteo Lambertini @matteolambe   Follow ASCO on social media:     @ASCO on Twitter    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. Matteo Lambertini: Consulting or Advisory Role: Roche, Novartis, Lilly, AstraZeneca, Pfizer, MSD, Exact Sciences, Gilead Sciences, Seagen, Menarini, Nordic Pharma Speakers' Bureau: Takeda, Roche, Lilly, Novartis, Pfizer, Sandoz, Ipsen, Knight Therapeutics, Libbs, Daiichi Sankyo, Gilead Sciences, AstraZeneca, Menarini, AstraZeneca, Menarini Research Funding (Inst.): Gilead Sciences Travel, Accommodations, Expenses: Gilead Sciences, Daiichi Sankyo Europe GmbH, Roche

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA information, and to apply for credit, please visit us at PeerView.com/UDA865. CME/MOC/NCPD/CPE/AAPA credit will be available until September 16, 2026.The Path to Viral Hepatitis Elimination: Enhancing Screening, Vaccination, Treatment, and Care In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Hepatitis B Foundation. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis program has been supported by an independent educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA information, and to apply for credit, please visit us at PeerView.com/UDA865. CME/MOC/NCPD/CPE/AAPA credit will be available until September 16, 2026.The Path to Viral Hepatitis Elimination: Enhancing Screening, Vaccination, Treatment, and Care In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Hepatitis B Foundation. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis program has been supported by an independent educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA information, and to apply for credit, please visit us at PeerView.com/UDA865. CME/MOC/NCPD/CPE/AAPA credit will be available until September 16, 2026.The Path to Viral Hepatitis Elimination: Enhancing Screening, Vaccination, Treatment, and Care In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Hepatitis B Foundation. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis program has been supported by an independent educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA information, and to apply for credit, please visit us at PeerView.com/UDA865. CME/MOC/NCPD/CPE/AAPA credit will be available until September 16, 2026.The Path to Viral Hepatitis Elimination: Enhancing Screening, Vaccination, Treatment, and Care In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Hepatitis B Foundation. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis program has been supported by an independent educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA information, and to apply for credit, please visit us at PeerView.com/UDA865. CME/MOC/NCPD/CPE/AAPA credit will be available until September 16, 2026.The Path to Viral Hepatitis Elimination: Enhancing Screening, Vaccination, Treatment, and Care In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Hepatitis B Foundation. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis program has been supported by an independent educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

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JCO PO authors Dr. Abhishek Tripathi and Dr. Salvador Jaime-Casas at City of Hope Comprehensive Cancer Center share insights into their article, “Comparative Genomic Characterization of Small Cell Carcinoma of the Bladder Compared With Urothelial Carcinoma and Small Cell Lung Carcinoma.”  Host Dr. Rafeh Naqash and Drs. Tripathi and Jaime-Casas discuss a novel understanding of the genomic alterations underlying SCBC, revealing actionable mutations that could serve as potential targets for improved clinical outcomes. TRANSCRIPT Dr. Rafeh Naqash: Hello and welcome to JCO Precision Oncology Conversations, where we bring you engaging conversations with authors of clinically relevant and highly significant JCO PO articles. I am your host, Dr. Dr. Rafeh Naqash, Podcast Editor for JCO Precision Oncology and Associate Professor at the OU Health Stephenson Cancer Center at the University of Oklahoma. Today, I am thrilled to be joined by Dr. Abhishek Tripathi, Associate Professor in the Department of Medical Oncology and Experimental Therapeutics Research at the City of Hope Comprehensive Cancer Center, as well as his mentee, Dr. Salvador Jaime-Casas, postdoctoral research fellow and first author of the JCO Precision Oncology article entitled "Comparative Genomic Characterization of Small Cell Carcinoma of the Bladder Compared with Urothelial Carcinoma and Small Cell Lung Carcinoma". At the time of this recording, our guest disclosures will be linked in the transcript. Abhishek and Salvador, welcome to our podcast and thank you for joining us today. This is a very interesting topic given that at least the landscape for neuroendocrine carcinomas, where small cell lung cancer is on one end of the spectrum, has been changing, at least on the lung cancer side, with recent approvals and some new ADCs. So, of course, understanding the genomic and transcriptomic similarities or differences between pulmonary small cell and extrapulmonary small cell is of huge interest. Could you tell us a little bit about small cell bladder cancer, current approaches to treatment of small cell bladder cancer, and then why you wanted to investigate that in this project as far as the genomic differences or similarities are concerned? Dr. Salvador Jaime-Casas: Well, first of all, thank you very much for having me. I am very excited to be here. And really what served as backbone for this research project was the notion that there is a currently evolving genomic landscape in the area of bladder cancer. We know this is a highly heterogeneous disease when it comes to molecular underpinnings and mutational profile. Specifically, we know that the most common histologic subtype is urothelial carcinoma. Small cell bladder cancer represents a histology that is found in less than 1% of all bladder cancer cases. However, it is one of the most aggressive histologies. It presents with a very poor prognosis to patients and very poor response to treatment, which is why we attempted to really elucidate what is the mutational profile behind this and provide a comparison contrast between small cell bladder cancer, small cell lung cancer, and conventional urothelial carcinoma. As your question mentioned, in terms of treatment, the conventional urothelial carcinoma and small cell bladder cancer are two distinct pathways when it comes to treatment algorithms. We know that in the current era there are newer and newer drugs being developed for conventional urothelial carcinoma. We have perioperative immunotherapy in the context of metastatic disease. We have antibody-drug conjugates such as enfortumab vedotin. But really, this amazing track record of drug development hasn't been mirrored in small cell bladder cancer. And here most of the therapy is usually extrapolated from studies from other small cell histologies like you mentioned earlier, small cell lung cancer has given some form of background in terms of what therapies are used here. Cytotoxic chemotherapy, for some patients with localized disease and small cell bladder cancer, concurrent chemotherapy and radiotherapy or perioperative cytotoxic chemotherapy have been the cornerstone of treatment for many years now. However, like I mentioned, the oncologic outcomes are very suboptimal when it comes to comparing it with other disease histologies, which is why we really wanted to describe the landscape here and provide this comparison across three different groups. For this particular study, we leveraged the Tempus dataset. So, include patients with urothelial carcinoma with small cell bladder cancer and small cell lung cancer. We included their demographic information, as well as the frequency of most common genomic alterations identified. And really, it was a very comparable Table 1. We see the demographic data across the three groups was very similar. One key thing that we identified was the female prevalence was a little bit lower in patients with small cell bladder cancer when compared to small cell lung cancer. But other than that, the age, race, ethnicity, was comparable across groups, and even the smoking history. Most of the patients in this cohort were former smokers, which we believe comes to explain that regardless of any mutational profile that we talked about in a few minutes, there are shared commonalities between these histologies and shared environmental exposures and risk factors that are going to be implicated in the disease biology for these three histologies. Dr. Rafeh Naqash: Thank you so much, Salvador, for that useful background. I would like to shift to Abhishek real quick. Abhishek, you are a practicing clinician, you have led several studies in the GU space, especially bladder. Based on what you see in the small cell lung cancer space, how drug development is shaping up, which aligns with what you are trying to evaluate in this paper as targets, how do you see some of that being implemented for small cell bladder cancer in the current era and age? Abhishek Tripathi: Thanks so much for the excellent question, Rafeh. As a GU investigator, small cell bladder cancer has always lagged behind in some regards regarding enrollment abilities for the novel clinical trials. And small cell lung cancer has paved the way and led the development of a lot of these drugs across the board. With the most recent sort of drugs targeting DLL3 already approved and several antibody-drug conjugates currently in development. That actually translates really well to how we should approach drug development in bladder cancer. What we saw in the study is that although there are overlaps and similarities between small cell lung cancer and small cell bladder cancer, there are also certain differences. So the long-term assumption that all therapies for small cell bladder cancer can be extrapolated to small cell bladder], may or may not be true, and I think it is high time that we specifically investigate these novel agents in tissue-specific small cell carcinomas. To that effect, we are excited to be participating in trials that are looking at some of the novel DLL3 targeted agents, specifically bispecific antibodies and T cell engagers so to speak, and antibody-drug conjugates that are now starting to open enrollment specifically in non-lung cancer cohorts to evaluate its efficacy. So overall, I think studies like this have the opportunity to identify more putative targets for organ-specific development of these novel agents. Dr. Rafeh Naqash: Absolutely, I could not agree more. I think tumor-agnostic therapies definitely have a place, but not all therapies work the same in different tumors with a similar histological or genomic background because there are definitely differences. So now going to the comparison that Salvador, you guys did in this project, could you help us understand what are some of the things you looked at, what were some of the commonalities and the differences, and what were some of the conceptual thoughts that come out from those results? Dr. Salvador Jaime-Casas: Of course. So, the first thing that we identified was which were the most frequent molecular alterations across these histologies. We actually provided a table showcasing how the most common mutations that we identified were TP53, TERT, RB1. However, like Dr. Tripathi mentioned, the distinction between these histologies is notable in the sense that some are more predominant in small cell-pertaining cancers such as bladder cancer and lung cancer. While some others are more common in bladder-pertaining malignancies like urothelial carcinoma and small cell bladder cancer. For instance, we saw that TP53 and RB1 were significantly more evident in small cell histologies, both small cell bladder cancer and small cell lung cancer, as opposed to conventional urothelial carcinoma, which really this mirrors what is known about these mutations and what has been published. These are markers associated with more aggressive disease with a worse prognosis and even to resistance to treatment. We also identified how TERT mutations were characteristically more prevalent in small cell bladder cancer as opposed to small cell lung cancer, as well as in urothelial carcinoma. TERT mutations were more commonly identified than in small cell lung cancer. And we give a long list of these mutations that we identified, but really what we wanted to underscore here was, A, the most common mutations across histologies; B, the most common co-occurring mutations where we saw that these are not mutually exclusive. A lot of patients had co-occurring TP53 and RB1 or RB1 and TERT or RB1 and ARID1A, really elucidating how heterogeneous this molecular landscape is across histologies. And the third one that we believe really brings down the clinical impact of this research was evidencing the idea of clinically actionable mutations. We also provided a table here showcasing how mutations like FGFR, DLL notch pathway, HER2, were evident in these histologies, and what is the current status of some clinical trials evaluating different drug designs for these mutations. Like Dr. Tripathi mentioned in the context of FGFR, approximately 6% of our cohort with small cell bladder cancer showcased mutations in FGFR3. However, up to 14% of them had mutations in any FGFR gene, which really underscores the notion that drugs like erdafitinib, which have been introduced in the market in recent years, could potentially showcase some response in the space of small cell bladder cancer. We actually provide the description of two trials, phase two, phase three trials, that are evaluating erdafitinib in the context of high-risk non-muscle invasive bladder cancer and even metastatic urothelial carcinoma. Like Dr. Tripathi mentioned as well, antibody-drug conjugates, another very interesting area of drug development targeting HER2, we included evidence on how disitamab vedotin and trastuzumab deruxtecan are currently being explored across different phase two and phase three clinical trials, both as part of basket trial designs for solid malignancies expressing HER2, but also for patients with urothelial carcinoma where there is evidence of HER2 expression. So, we believe that the landscape is shifting in the right direction in the sense that therapies are becoming much more personalized and targeted against these known molecular profiles. Dr. Rafeh Naqash: Thank you, Salvador, for summarizing some of those very interesting results and providing a very unique conceptual context to that. I would like to go to Abhishek this last portion. Of course, I am sure you guys will expand on this work and there are a lot of other interesting things that will likely come out from this work and hopefully you will publish that in JCO PO. But one of the very important things that I wanted to highlight from this podcast specifically was the science is obviously very interesting, but I feel the more important interesting aspect is giving trainees and fellows, residents, mentorship opportunities, mentoring them and giving them lead roles in projects like this, which is what Dr. Tripathi has successfully done for you in this project, Salvador. So, Abhishek, as somebody I have known for a couple of years now, more than a couple of years, as a very successful clinical translational investigator in the GU space in the early phase setting, Abhishek, really briefly, within a minute, could you tell us about your journey and what are some of the things that have worked for you as an early career investigator that you have learned from, and then your journey of mentorship, how has that been for you and what are some of the things that you take home from your mentorship role? Abhishek Tripathi: Absolutely. And as you mentioned, mentorship has been pivotal for all early career investigators for them to really succeed. So, my journey, as you know, I started off as an early career investigator at another institution, and I think I owe it to my mentors even at that time and even now who are helping me develop some of these newer translational and clinical trial ideas, creating opportunities where we could really showcase some of the interesting work that we are doing. That actually goes a long way in terms of creating independence as an established investigator. And I think the sooner we start off with mentorship prospects, I think the better it is. And paying it forward, I think I have been lucky to have mentees like Salvador who are just extremely talented, really committed, and goal-oriented. He really led the project right from the beginning in terms of initial analyses and looking up all the sort of correlative studies that we could do and the contextual data between small cell lung cancer and bladder cancer that we have delved into for the past several years. And it really showcases the ability of young mentees like Salvador to really excel given the right guidance and the support. As a mentor, it has been a really rewarding experience. It is really helpful to actually learn from some of these mentees as well as to approach the same problem from a different angle and different thought process and guide them through the study. So, it has been incredibly helpful and rewarding both being a mentee and a mentor over the past several years as I have transitioned. Dr. Rafeh Naqash: Thank you, Abhishek, for those very insightful comments on how both being a mentee and being a mentor helps shape you as an individual as well. And then you take a lot of pride in the success of your mentees. Now real quick, Salvador, could you tell us a little bit about yourself, you know, how you ended up at City of Hope under Dr. Tripathi's mentorship and what are some of the next important things that you are looking forward to doing? Dr. Salvador Jaime-Casas: So, a little bit about who I am. I did medical school in Mexico City. I was born and raised there, and towards the end of my medical training, I started to be engaged in research projects. And through one of my mentors in Mexico, I was actually introduced to the team here at City of Hope, including Dr. Tripathi. And through this, we got the opportunity to have some conversations about what I wanted to do, become a physician-researcher in the area of genitourinary oncology and hopefully my transition to residency in a few years. And that is how I came to be his mentee here at City of Hope. I think it has been a very rewarding experience, like Dr. Tripathi said, having such an incredible mentor and really being with him both in the academic setting and in the clinical setting, in patients with clinic, seeing this curiosity and all these clinical trials, all of this evidence that we have coming together to generate this insight. Dr. Rafeh Naqash: Thank you so much for both the scientific insights, as well as the journey of being a mentee for you, Salvador, and as a mentor for you, Abhishek. I really enjoyed talking to you guys about both aspects here today and hopefully we will see more of your work, Abhishek and Salvador, as far as understanding the transcriptomic heterogeneity in neuroendocrine tumors or neuroendocrine cancers of the bladder. Dr. Salvador Jaime-Casas: Thank you very much. Thank you for having us. Dr. Rafeh Naqash: Thank you for listening to JCO Precision Oncology Conversations. Do not forget to give us a rating or review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at ASCO.org/podcasts. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.   Dr. Abhishek Tripathi Disclosures Consulting or Advisory Role:  Company: Aadi biosciences, Seattle Genetics/Astellas, Exelixis, Bayer, Gilead Sciences, Pfizer, Deka biosciences Speakers' Bureau: Company: Sanofi

Dr. Sumanta (Monty) Pal and Dr. Petros Grivas discuss innovative new intravesical therapies and other recent advances in the treatment of non-muscle invasive bladder cancer. TRANSCRIPT Dr. Sumanta (Monty) Pal: Hello and welcome. I'm Dr. Monty Pal here at the ASCO Daily News Podcast. I'm a medical oncologist and professor and vice chair of academic affairs at the City of Hope Comprehensive Cancer Center in Los Angeles. And I'm really delighted to be your new host here. Today's episode is going to really sort of focus on an area near and dear to my heart, something I actually see in the clinics, and that's bladder cancer. We're specifically going to be discussing non-muscle invasive bladder cancer, which actually comprises about 75% of new cases. Now, in recent years, there's been a huge shift towards personalized bladder-preserving strategies, including innovative therapies and new agents that really are reducing reliance on more primitive techniques like radical cystectomy and radiation therapy. And I'm really excited about this new trend. And really at the forefront of this is one of my dear friends and colleagues, Dr. Petros Grivas. He's a professor in the Department of Medicine and Division of Hematology Oncology at the University of Washington. It's going to take a while to get through all these titles. He's taken on a bunch of new roles. He is medical director of the International Program, medical director of the Local and Regional Outreach Program, and also professor in the Clinical Research Division at the Fred Hutch Cancer Center. Petros, welcome to the program. Dr. Petros Grivas: Thank you so much, Monty. It's exciting for me to be here. Dr. Sumanta (Monty) Pal: Just FYI for our audience, our disclosures are available in the transcript of this episode.  We're going to get right into it, Petros. Non-muscle invasive bladder cancer, this is a really, really challenging space. We see a lot of recurrence and progression of the disease over time, about 50% to 70% of patients do have some recurrence after initial treatment, and about 30% are ultimately going to progress on to muscle-invasive or metastatic disease. Now, I will say that when you and I were in training, non-muscle invasive bladder cancer was something that was almost relegated to the domain of the urologist, right? They would use treatments such as BCG (Bacillus Calmette-Guérin) in a serial fashion. It was rare, I think, for you and I to really enter into this clinical space, but that's all changing, isn't it? I mean, can you maybe tell us about some of the new therapies, two or three that you're really excited about in this space? Dr. Petros Grivas: Monty, you're correct. Traditionally and conventionally, our dear friends and colleagues in urology have been managing patients with non-muscle invasive bladder cancer. The previous term was superficial bladder cancer. Now, it has changed, to your point, to non-muscle invasive bladder cancer. And this has to do with the staging of this entity. These tumors in superficial layers of bladder cancer, not invading the muscularis propria, the muscle layer, which makes the bladder contract for urine to be expelled. As you said, these patients have been treated traditionally with intravesical BCG, one of the oldest forms of immunotherapy that was developed back in the 1970s, and this is a big milestone of immunotherapy development. However, over the years, in the last 50 years, there were not many options for patients in whom the cancers had progression or recurrence, came back after this intravesical BCG. Many of those patients were undergoing, and many of them still may be undergoing, what we call radical cystectomy, meaning removal of the bladder and the lymph nodes around the bladder. The development of newer agents over the last several years has given the patients the option of having other intravesical therapies, intravesical meaning the delivery of drugs, medications inside the bladder, aiming to preserve the bladder, keep the bladder in place. And there are many examples of those agents. Just to give you some examples, intravesical chemotherapy, chemotherapy drugs that you and me may be giving intravenously, some of them can be given inside the bladder, intravesical installation. One example of that is a combination of gemcitabine and docetaxel. These drugs are given in sequence one after the other inside the bladder, and they have seen significant efficacy, good results, again, helping patients keeping the bladder when they can for patients with what we call BCG unresponsive non-muscle invasive bladder cancer. And again, there's criteria that the International Bladder Cancer Group and the FDA developed, how to define when BCG fails, when we have BCG unresponsive non-muscle invasive bladder cancer. Dr. Sumanta (Monty) Pal: And we're actually going to get into some of the FDA requirements and development pathways and so forth. What I'm really interested in hearing, and I'm sure our audience is too, are maybe some of the new intravesical treatments that are coming around. I do think it's exciting that the gemcitabine and docetaxel go into the bladder indeed, but what are some of the top new therapies? Pick two or three that you're excited about that people should be looking out for in this intravesical space. Dr. Petros Grivas: For sure, for sure. In terms of the new up-and-coming therapies, there are a couple that come to mind. One of them is called TAR-200, T-A-R 200. This agent is actually a very interesting system. It's an intravesical delivery of a chemotherapy called gemcitabine, the one that I just mentioned a few minutes ago, that is actually being delivered through what we call a pretzel, which is like a rounded [pretzel-shaped] structure working like an osmotic pump, and that is being delivered inside the bladder intravesically by urologists. And this drug is releasing, through the osmotic release mechanism, this chemotherapeutic drug, gemcitabine, inside the bladder. And this can be replaced once every 3 weeks in the beginning. And the data so far from early-phase trials are really, really promising, showing that this agent may be potentially regulatory approved down the road. So TAR-200 is something to keep in mind. And similarly, in the same context, there is a different drug that also uses the same mechanism, and this osmotic release, this pretzel, it's just encoded with a different agent. The different agent is an FGFR inhibitor, a target therapy called erdafitinib, a drug that you and me may give in patients with metastatic urothelial carcinoma if they have an FGFR3 mutation or fusion. And that drug is called TAR-210. Dr. Sumanta (Monty) Pal: And can I ask you, in that setting, do you have to have an FGFR3 mutation to receive it? Or what is the context there? Dr. Petros Grivas: So for TAR-210, TAR-2-1-0, usually there is a checking to see if there is an FGFR3 mutation or fusion. And the big question, Monty, is do we have adequate tissue, right? From a limited tissue on what we call the TURBT, right, that urologists do. And now there is a lot of development in technology, for example, urine circulating tumor DNA to try to detect these mutations in the urine to see whether the patient may be eligible for this TAR-210. Both of those agents are not FDA approved, but there are significant promising clinical trials. Dr. Sumanta (Monty) Pal: So now let's go to a rapid-fire round. Give us two more agents that you're excited about in this intravesical space. What do you think? Dr. Petros Grivas: There is another one called cretostimogene. It's a long name. Dr. Sumanta (Monty) Pal: They really make these names very easy for us, don't they? Dr. Petros Grivas: They are not Greek names, Monty, I can tell you, you know. Even my Greek language is having trouble pronouncing them. The cretostimogene, it's actually almost what we call a growth factor, a GM-CSF. The actual name of this agent is CG0070. This is a replicating mechanism where GM-CSF is replicating in cells. And this agent has shown significant results again, like the TAR-200, in BCG unresponsive non-muscle invasive bladder cancer. I would say very quickly, two agents that actually were recently approved and they're already available in clinical practice, is nadofaragene firadenovec, another long name. That's a non-replicating vector that has the gene of interferon alfa-2b that stimulates the immune system in the bladder. It's given once every 3 months. And the last one that was, as I mentioned, already FDA approved, it's an interleukin-15 superagonist. It's another long name, which is hard to pronounce, but I will give it a try. It's a drug that was recently actually approved also in the UK. The previous name was N-803. It's given together with BCG as a combination for BCG unresponsive non-muscle invasive bladder cancer. Dr. Sumanta (Monty) Pal: This is a huge dilemma, I think, right? Because if you're a practicing, I'm going to say urologist for the moment, I guess the challenge is how do you decide between an IL-15 superagonist? How do you decide between a pretzel-eluting agent? How do you decide between that and maybe something that's ostensibly, I'm going to guess, cheaper, like gemcitabine and docetaxel? What's sort of the current thinking amongst urologists? Dr. Petros Grivas: Multiple factors play into our account when the decision is being made. I discuss with urologists all the time. It's not an easy decision because we do not have head-to-head comparisons between those agents. As you mentioned, intravesical chemotherapy with gemcitabine and docetaxel has been used over the years and this is the lowest cost, I would say, the cheapest option with good efficacy results. Obviously, the nadofaragene firadenovec every 3 months and the interleukin-15 superagonist, N-803, plus BCG have also been approved. The question is availability of those agents, are they available? Are they reimbursed? Cost of those agents can come into play. Frequency of administration, you know, once every 3 months versus more frequent. And of course, the individual efficacy and toxicity data, preference of the patients; sometimes the provider, the urologist, may have something that they may be more familiar with. But we lack this head-to-head comparison. Of course, I want to make sure I mention that radical cystectomy may still be the option for appropriate patients. So that complicates also the decision making and has to be individualized, customized, and personalized, taking into account all those factors. And there is not one size fitting all. Dr. Sumanta (Monty) Pal: So I think we discussed five intravesical therapies. As you point out, and you know, I'm going to get some calls about this: I think I referred to radical cystectomy as being a more primitive procedure. Not true at all. I think it's something that still is, you know, a mainstay of management in this disease space. But I guess it gets even more complicated, am I right, Petros? Because now we have systemic therapies that we can actually apply in this non-muscle invasive setting for at this point, refractory disease. Can you maybe just give us a quick two-minute primer on that? Dr. Petros Grivas: Absolutely, and systemic therapies now come into play, as you said. And a classical example of that, Monty, came from the KEYNOTE-057 trial that we published about 6 years ago. This is intravenous pembrolizumab, given intravascularly, intravenously, as opposed to the previously discussed intravesical administration of agents. Pembrolizumab was tested in that KEYNOTE-057 trial and showed efficacy about, I would say, one out of five patients, about 20%, had a complete response of the tumor in the bladder in a year after starting the treatment. Again, it's hard to compare across different agents, but obviously when we give something intravenously, there is a risk of toxicity, side effects systemically, what we call immune-related adverse events. And this can also play in the decision making, right? When you have intravesical agents versus intravascular agents, there is different toxicity profiles in terms of systemic toxicity. But intravenous pembrolizumab has been an option, FDA approved, since, if I remember, it was early 2020 when this became FDA approved. There are other agents being tested in this disease, but like atezolizumab through the SWOG study that Dr. Black and Dr. Singh led, but atezolizumab is not FDA approved for this indication. Again, this is for BCG unresponsive, high-risk, non-muscle invasive bladder cancer. Dr. Sumanta (Monty) Pal: So maybe teach us how it works, for instance, at an expert center like the Fred Hutch. When you see a patient with non-muscle invasive bladder cancer, there's obviously the option of surgery, there's the intravesical therapies, which I imagine the urology team is still really at the helm of. But then, I guess there has to be consideration of all options. So you've got to bring up systemic therapy with agents like pembrolizumab. In that context, are you involved that early on in the conversation? Dr. Petros Grivas: That's a great discussion, Monty. Paradigm is shifting as we mentioned together. The urologists have been treating these patients and still they are the mainstay of the treaters, the managers in this disease. But medical oncologists come to play more and more, especially with the FDA approval of intravenous pembrolizumab about 5 years ago [GC1]  [KM2] . We have the concept of multidisciplinary bladder cancer clinic here at Fred Hutch and University of Washington. This happens every Tuesday morning, and we're very excited because it's a one-stop shop for the patients. We have the urologist, a medical oncologist, radiation oncologist, and experts from radiology and pathology, and we all review cases specifically with muscle-invasive bladder cancer. But every now and then, we see patients with BCG unresponsive non-muscle invasive bladder cancer. And this is where we discuss and we talk to the patient about pros and cons of all those options. And that's a classic example where medical oncologists may start to see those patients and offer their input and expertise. In addition to that, sometimes we have clinical trials, we may see these patients because there are systemic agents that may be administered in this setting. We have the SunRISe trial program that includes also a systemically administered checkpoint inhibitor. So that's another example where we see patients either in the context of multi-clinic or in individual solo clinics to counsel the patients about the pros and cons of the systemically administered agents in the context of clinical trials. Usually checkpoint inhibitors are the class of agents that are being tested in this particular scenario. Dr. Sumanta (Monty) Pal: I can see a scenario where it's really going to require this sort of deep dive, much in the way that we do for prostate cancer, for instance, where the medical oncologist is involved very early on and planning out any sort of systemic therapy component of treatment or at the very least, at least spelling out those options. I think it's going to be really interesting to see what this space looks like 5 or 10 years down the road. In closing, I wanted to go through something that I think is so different in this space, at least for the time being, and that is the paradigm for FDA approval. When you and I have our fellows in the clinics, we always say, “Look, you know, the paradigm in this disease and that disease and the other disease needs to be phase 3 randomized trials, right? Big thousand patient experiences where you're testing clinical endpoints.” That's tough in non-muscle invasive bladder cancer, right? Because thankfully, outcomes can actually be quite good, you know, in this setting, right? It's tough to actually estimate overall survival in some of these early-stage populations. Tell me what the current regulatory bar is, and this is a tough thing to do in 2 minutes or less but tell me where you see it headed. Dr. Petros Grivas: You alluded to that before, Monty, when I was giving the background and we talked about the regulatory approval. And I have to very quickly go back in time about 10 years ago because it's important for context that can help us in other disease types too. We had workshops with the FDA and the NCI with the help of the International Bladder Cancer Group and other colleagues. And we try to define a framework, what endpoints are meaningful for those patients in this disease. It was a multidisciplinary, multiple stakeholders meeting, where we tried to define what is important for patients. What are the available agents? What are the trial designs we can accept? And what are the meaningful endpoints that the regulatory agencies can accept for regulatory approval? And that was critical in that mission because it allowed us to design clinical trials, for example, single-arm trials in a disease where there was no standard of care. There was intravesical valrubicin and chemotherapy anthracycline that was approved for many years, but was not practically used in clinical practice, despite being approved, the valrubicin. And because of that, the FDA allowed these single-arm trials to happen. And obviously the endpoint was also discussed in that meeting. For example, for carcinoma in situ, complete response, clinical complete response, because the bladder remains intact in many patients, clinical complete response was a meaningful primary endpoint, also duration of response is also very important. So what is the durable clinical complete response in 1 year or 18 months is relevant. And when you have papillary tumors like Ta or T1 with CIS, for papillary tumors, event-free survival becomes one of the key endpoints and you look at it over time, for example, at 12 or 18 months, what is the event-free survival? So clinical complete response, duration of response, event-free survival, depending on the CIS presence or papillary tumors, I think these are endpoints that have allowed us to design those trials, get those agents approved.  Now, the question going forward, Monty, and we can close with that is, since now we have the embarrassment of riches, many more options available compared to where we were 6 and 7 years ago, is now the time to do randomized trials? And if we do randomized trials, which can be the control group? Which of those agents should be allowed to be part of the control group? These are ongoing discussions right now with the NCI, with other agencies, cooperative groups, trying to design those trials and move forward from here.[GC3]  Dr. Sumanta (Monty) Pal: Well, it's awesome to have you here on the program so we can get some early looks into some of these conversations. I mean, clearly, you're at the table at a lot of these discussions, Petros. So I want to thank you for sharing your insights with us today. This was just tremendous. Dr. Petros Grivas: Thank you, Monty. You know, patients in the center, I just came back from the Bladder Cancer Advocacy Network meeting in Washington, D.C., and we discussed all those questions, the topics you very eloquently mentioned and asked me today, and patients gave us great feedback and patients guide us in that effort. Thank you so, so much for having me and congratulations for the amazing podcast you're doing. Dr. Sumanta (Monty) Pal: Oh, cheers, Petros, thanks so much.  And thank you to the listeners who joined us today. If you really like the insights that you heard on this ASCO Daily News Podcast, please rate, review, and subscribe wherever you get your podcasts. Thanks, everyone. 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. Sumanta (Monty) Pal  @montypal  Dr. Petros Grivas @PGrivasMDPhD   Follow ASCO on social media:     @ASCO on Twitter    ASCO on Bluesky   ASCO on Facebook     ASCO on LinkedIn     Disclosures:    Dr. Sumanta (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. Petros Grivas: Consulting or Advisory Role: Merck, Bristol-Myers Squibb, AstraZeneca, EMD Serono, Pfizer, Janssen, Roche, Astellas Pharma, Gilead Sciences, Strata Oncology, Abbvie, Bicycle Therapeutics Replimune, Daiichi Sankyo, Foundation Medicine, Bicycle Therapeutics, Eli Lilly, Urogen Pharma, Tyra Biosciences Research Funding (Inst.): Bristol-Myers Squibb, Merck, EMD Serono, Gilead Sciences, Acrivon Therapeutics, ALX Oncology, ALX Oncology, Genentech Travel, Accommodations, Expenses: Gilead Sciences

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Are you looking to save time, make money, and start winning with less risk? Then head to https://www.ovtlyr.com.In this exclusive video, we're diving deep into a trading session that's packed with powerful insights and game-changing strategies. Get ready to uncover the secrets of the Golden Ticket Trading strategy and learn how to navigate the market with confidence and precision. This video takes you inside a live trading room to reveal a plan and show you exactly how the market is being traded today. We'll start by breaking down a truly fascinating and controversial market buy signal that has everyone talking. You'll get a sneak peek at the new OVTLYR 4.0 and see firsthand how signal noise is being reduced to give you a clearer picture of the market trends. This is your chance to see the future of trading tools before anyone else.There is also a major announcement that is hard to believe: SoFi was just bought. After years of talking smack about it, multiple SoFi contracts are now owned, and the excitement is high. The decision will be explained and why this trade is a massive part of the current strategy. Plus, several other stocks bought today will be revealed.This video isn't just about new trades; it's also about managing current positions like a professional. The open trades in VXX, Gilead Sciences, and GME will be walked through. You'll learn the powerful technique of rolling options to keep trades alive, take partial profits, and free up capital for new opportunities. This is a critical skill that every serious trader needs to master.A core tenet of the trading philosophy will also be shared: the importance of trading psychology and risk reduction. We'll discuss why you should never set profit targets and how to have a solid plan in place to reduce risk before you even think about putting on a new trade. This disciplined approach is the foundation of long-term success.The mission is to help you save time, make money, and start winning with less risk, together.Don't forget to hit the like button and share this video with everyone you know. The best way to give back for these valuable insights is to help spread the word about the OVTLYR trading philosophy.Gain instant access to the AI-powered tools and behavioral insights top traders use to spot big moves before the crowd. Start trading smarter today

Dr. Hope Rugo and Dr. Kamaria Lee discuss the prevalence of financial toxicity in cancer care in the United States and globally, focusing on breast cancer, and highlight key interventions to mitigate financial hardship. TRANSCRIPT  Dr. Hope Rugo: 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 your host, Dr. Hope Rugo. I'm the director of the Women's Cancer Program and division chief of breast medical oncology at the City of Hope Cancer Center, and I'm also the editor-in-chief of the Educational Book. Rising healthcare costs are causing financial distress for patients and their families across the globe. Patients with cancer report financial toxicity as a major impediment to their quality of life, and its association with worse outcomes is well documented. Today, we'll be discussing how patients with breast cancer are uniquely at risk for financial toxicity. Joining me for this discussion is Dr. Kamaria Lee, a fourth-year radiation oncology resident and health equity researcher at MD Anderson Cancer Center and a co-author of the recently published article titled, "Financial Toxicity in Breast Cancer: Why Does It Matter, Who Is at Risk, and How Do We Intervene?" Our full disclosures are available in the transcript of this episode.  Dr. Lee, it's great to have you on this podcast. Dr. Kamaria Lee: Hey, Dr. Rugo. Thank you so much for having me. I'm excited to be here today. I also would like to recognize my co-authors, Dr. Alexandru Eniu, Dr. Christopher Booth, Molly MacDonald, and Dr. Fumiko Chino, who worked on this book chapter with me and did a fantastic presentation on the topic at ASCO this past year. Dr. Hope Rugo: Thanks very much. We'll now just jump into the questions. We know that rising medical costs contribute to a growing financial burden on patients, which has [GC1]  [JG2]  been documented to contribute to lower quality-of-life, compromised clinical care, and worse health outcomes. How are patients with breast cancer uniquely at risk for financial toxicity? How does the problem vary within the breast cancer population in terms of age, racial and ethnic groups, and those who have metastatic disease? Dr. Kamaria Lee: Breast cancer patients are uniquely at risk of financial toxicity for several reasons. Three key reasons are that breast cancer often requires multimodal treatment. So this means patients are receiving surgery, many receive systemic therapies, including hormonal therapies, as well as radiation. And so this requires care coordination and multiple visits that can increase costs. Secondly, another key reason that patients with breast cancer are uniquely at risk for financial toxicity is that there's often a long survivorship period that includes long-term care for toxicities and continued follow-ups, and patients might also be involved in activities regarding advocacy, but also physical therapy and mental health appointments during their prolonged survivorship, which can also add costs. And a third key reason that patients with breast cancer are uniquely at risk for financial toxicity is that the patient population is primarily women. And we know that women are more likely to have increased caregiver responsibilities while also potentially working and managing their treatments, and so this is another contributor. Within the breast cancer population, those who are younger and those who are from marginalized racial/ethnic groups and those with metastatic disease have been shown to be at an increased risk. Those who are younger may be more likely to need childcare during treatment if they have kids, or they're more likely to be employed and not yet retired, which can be disrupted while receiving treatment. And those who are racial/ethnic minorities may have increased financial toxicity due to reasons that exist even after controlling for socioeconomic factors. And some of these reasons have been shown to be increased risk of job or income loss or transportation barriers during treatment. And lastly, for those with metastatic breast cancer, there can be ongoing financial distress due to the long-term care that is needed for treatment, and this can include parking, transportation, and medications while managing their metastatic disease. Dr. Hope Rugo: I think it is really important to understand these issues as you just outlined. There has been a lot of focus on financial toxicity research in recent years, and that has led to novel approaches in screening for financial hardship. Can you tell us about the new screening tools and interventions and how you can easily apply that to clinical practice, keeping in mind that people aren't at MD Anderson with a bunch of support and information on this but are in clinical practice and seeing many, many patients a day with lots of different cancers? Dr. Kamaria Lee: You're exactly right that there is incredible nuance needed in understanding how to best screen for financial hardship in different types of practices. There are multiple financial toxicity tools. The most commonly used tool is the Comprehensive Score for Financial Toxicity, also known as the COST tool. In its full form, it's an 11-item survey. There's also a summary question as well. And these questions look at objective and subjective financial burden, and it uses a five-point Likert scale. For example, one question on the full form is, "I know that I have enough money in savings, retirement, or assets to cover the cost of my treatment," and then patients are able to respond "not at all" to "very much" with a threshold score for financial toxicity risk. Of course, as you noted, one critique of having an 11-item survey is that there's limited time in patient encounters with their providers. And so recently, Thom et al validated an abbreviated two-question version of the COST tool. This validation was done in an urban comprehensive cancer center, and it was found to have a high predictive value to the full measure. We note which two questions are specifically pulled from the full measure within the book chapter. And this is one way that it can be easier for clinicians who are in a busier setting to still screen for financial toxicity with fewer questions. I also do recommend that clinicians who know their clinic's workflow the best, work with their team of nurses, financial navigators, and others to best integrate the tool into their workflow. For some, this may mean sending the two-item survey as a portal message so that patients can answer it before consults. Other times, it could mean having it on the tablet that can be done in the clinic waiting room. And so there are different ways that screening can be done, even in a busy setting, and acknowledging that different practices have different amounts of resources and time. Dr. Hope Rugo: And where would people access that easily? I recognize that that information is in your chapter, or your article that's on PubMed that will be linked to this podcast, but it is nice to just know where people could easily access that online. Dr. Kamaria Lee: Yes, and so you should be able to Google ‘the COST measure', and then there is a website that also has the forms as well. So it's also beyond the book chapter, Googling ‘the COST measure', and then online they would be able to find access to the form. Dr. Hope Rugo: And how often would you do that screening? Dr. Kamaria Lee: So, I think it's definitely important that we are as proactive as possible. And so initially, I recommend that the screening happens at the time of diagnosis, and so if it's done through the portal, it can be sent before the initial consult, or again, however, is best in the workflow. So at the time of diagnosis and then at regular intervals, so throughout the treatment process, but then also into the follow-up period as well to best understand if there's still a financial burden even after the treatments have been completed. Dr. Hope Rugo: I wonder if in the metastatic setting, you could do it at the change of treatment, you know, a month after somebody's changed treatment, because people may not be as aware of the financial constraints when they first get prescribed a drug. It's more when you hear back from how much it's going to cost. And leading into that, I think it's, what do you do with this? So, you know, this cost conversation is really important. You're going to be talking to the patient about the cost considerations when you, for example, see that there are financial issues, you're prescribing treatments. How do we implement impactful structured cost conversations with our breast cancer patients, help identify financial issues, and intervene? How do we intervene? I mean, as physicians often we aren't really all that aware, or providers, of how to address the cost. Dr. Kamaria Lee: Yes, I agree fully that another key time when to screen for financial toxicity is at that transition between treatments to best understand where they're at based off of what they've received previously for care, and then to anticipate needs when changing regimens, such as like you said in the metastatic setting. As we're collecting this information, you're right, we screen, we get this information, and what do we do? I do agree that there is a lack of knowledge among us clinicians of how do we manage this information. What is insurance? How do we manage insurance and help patients with insurance concerns? How do we help them navigate out-of-pocket costs or even the indirect costs of transportation? Those are a lot of things that are not covered in-depth in traditional medical training. And so it can be overwhelming for a lot of clinicians, not only due to time limitations in clinic, but also just having those conversations within their visit. And so what I would say, a key thing to note, is that this is another area for multidisciplinary care. So just as we're treating patients in a multidisciplinary way within oncology as we work with our medical oncology, surgical colleagues across the board, it's knowing that this is another area for multidisciplinary care. So the team members include all of the different oncologists, but it also includes team members such as financial counselors and navigators and social workers and even understanding nonprofit partners who we have who have money that can be set aside to help reduce costs for certain different aspects of treatment. Another thing I will note is that most patients with breast cancer often say they do want to have these conversations still with their clinicians. So they do still see a clinician as someone that can weigh in on the costs of their treatment or can weigh in on this other aspect of their care, even if it's not the actual medication or the radiation. And so patients do desire to hear from their clinicians about this topic, and so I think another way to make it feel less overwhelming for clinicians like ourselves is to know that even small conversations are helpful and then being knowledgeable about within your institution or, like I said, outside of it with nonprofits, being aware of who can I refer this patient to for continued follow-up and for more detailed information and resources. Dr. Hope Rugo: Are those the successful interventions? It's really referring to financial navigators? How do people identify? You know, in an academic center, we often will sort of punt this to social workers or our nurse navigators. What about in the community? What's a successful intervention example of mitigating financial toxicity? Dr. Kamaria Lee: I agree completely that the context at which people are practicing is important to note. So as you alluded to, in some bigger systems, we do have financial navigators and this has been seen to be successful in providing applications and assisting with applications for things such as pharmaceutical assistance, insurance applications, discount opportunities.  Another successful intervention are financial toxicity tumor boards, which I acknowledge might not be able to exist everywhere. But where this is possible, multidisciplinary tumor boards that include both doctors and nurses and social workers and any other members of the care team have been able to effectively decrease patients' personal spending on care costs and decrease co-pays through having a dedicated time to discuss concerns as they arise or even proactively. Otherwise, I think in the community, there are other interventions in regards to understanding different aspects of government programs that might be available for patients that are not, you know, limited to an institution, but that are more nationally available, and then again, also having the nonprofit, you know, partnerships to see other resources that patients can have access to.  And then I would also say that the indirect costs are a significant burden for many patients. So by that, I mean even parking costs, transportation, childcare. And so even though those aren't interventions necessarily with someone who is a financial navigator, I would recommend that even if it's a community practice, they discuss ways that they can help offset those indirect costs with patients with parking or if there are ways to help offset transportation costs or at least educate patients on other centers that may be closer to them or they can still receive wonderful care, and then also making sure that patients are able to even have appointments scheduled in ways that are easier for them financially.  So even if someone's receiving care out in the community where there's not a financial navigator, as clinicians or our scheduling teams, sometimes there are options to make sure if a patient wants, visits are more so on one day than throughout the week or many hours apart that can really cause loss of income due to missed work. And so there are also kind of more nuanced interventions that can happen even without a financial navigation system in place. Dr. Hope Rugo: I think that those are really good points and it is interesting when you think about financial toxicity. I mean, we worry a lot when patients can't take the drugs because they can't afford them, but there are obviously many other non-treatment, direct treatment-related issues that come up like the parking, childcare, tolls, you know, having a working car, all those kinds of things, and the unexpected things like school is out or something like that that really play a big role where they don't have alternatives. And I think that if we think about just drug costs, I think those are a big issue in the global setting. And your article did address financial toxicity in the global setting. International financial toxicity rates range from 25% of patients with breast cancer in high-income countries to nearly 80% in low- and middle-income countries or LMICs. You had cited a recent meta-analysis of the global burnout from cancer, and that article found that over half of patients faced catastrophic health expenditures. And of course, I travel internationally and have a lot of colleagues who are working in oncology in many countries, and it is really often kind of shocking from our perspective to see what people can get coverage for and how much they have to pay out-of-pocket and how much that changes, that causes a lot of disparity in access to healthcare options, even those that improve survival. Can you comment on the global impact of this problem? Dr. Kamaria Lee: I am glad that you brought this up for discussion as well. Financial toxicity is something that is a significant global issue. As you mentioned, as high as 80% of patients with breast cancer in low- and middle-income countries have had significant financial toxicity. And it's particularly notable that even when looking at breast cancer compared to other malignancies around the world, the burden appears to be worse. This has been seen even in countries with free universal healthcare. One example is Sri Lanka, where they saw high financial toxicity for their patients with breast cancer, even with this free universal healthcare. But there were also those travel costs and just additional out-of-hospital tests that were not covered. Also, literature in low- and middle-income countries shows that patients might also be borrowing money from their social networks, so from their family and their friends, to help cover their treatment costs, and in some cases, people are making daily food compromises to help offset the cost of their care. So there is a really large burden of financial toxicity generally for cancer globally, but also specifically in breast cancer, it warrants specific discussion. In the meta-analysis that you mentioned, they identified key risk factors of financial toxicity globally that included people who had a larger family size, a lower income, a lack of insurance, longer disease duration, so again, the accumulation of visits and costs and co-pay over time, and those who had multiple treatments. And so in the global setting, there is this significant burden, but then I will also note that there is a lack of literature in low-income countries on financial toxicity. So where we suspect that there is a higher burden and where we need to better understand how it's distributed and what interventions can be applied, especially culturally specific interventions for each country and community, there's less research on this topic. So there is definitely an increased need for research in financial toxicity, particularly in the global setting. Dr. Hope Rugo: Yes, and I think that goes on to how we hope that financial toxicity researchers will have approaches to large-scale multi-institutional interventions to improve financial toxicity. I think this is an enormous challenge, but one of the SWOG organizations has done some great work in this area, and a randomized trial addressing cancer-related financial hardship through the delivery of a proactive financial navigation intervention is one area that SWOG has focused on, which I think is really interesting. Of course, that's going to be US-based, which is how we might find our best paths starting. Do you think that's a good path forward, maybe that being able to provide something like that across institutions that are independent of being a cancer only academic center, or more general academic center, or a community practice? You know, is finding ways to help patients with breast cancer and their families understand and better manage financial aspects of cancer care on a national basis the next approach? Dr. Kamaria Lee: Yes, I agree that that is a good approach, and I think the proactive component is also key. We know that patients that are coming to us with any cancer, but including breast cancer, some of them have already experienced a financial burden or have recently had a job loss before even coming to us and having the added distress of our direct costs and our indirect costs. So I think being proactive when they come to us in regards to the additional burden that their cancer treatments may cause is key to try to get ahead of things as much as we can, knowing that even before they've seen us, there might be many financial concerns that they've been navigating.  I think at the national level, that allows us to try to understand things at what might be a higher level of evidence and make sure that we're able to address this for a diverse cohort of patients. I know that sometimes the enrollment can be challenging at the national level when looking at financial toxicity, as then we're involving many different types of financial navigation partners and programs, and so that can maybe make it more complex to understand the best approaches, but I think that it can be done and can really bring our understanding of important financial toxicity interventions to the next level. And then the benefit to families with the proactive component is just allowing them to feel more informed, which can help decrease anticipation, anxiety related to anticipation, and allow them to help plan things moving forward for themselves and for the whole family. Dr. Hope Rugo: Those are really good points and I wonder, I was just thinking as you were talking, that having some kind of a process where you could attach to the electronic health record, you could click on the financial toxicity survey questions that somebody filled out, and then there would be a drop-down menu for interventions or connecting you to people within your clinic or even more broadly that would be potential approaches to manage that toxicity issue so that it doesn't impact care, you know, that people aren't going to decide not to take their medication or not to come in or not to get their labs because of the cost or the transportation or the home care issues that often are a big problem, even parking, as you pointed out, at the cancer center. And actually, we had a philanthropic donor when I was at UCSF who donated a large sum of money for patient assistance, and it was interesting to then have these sequential meetings with all the stakeholders to try and decide how you would use that money. You need a big program, you need to have a way of assessing the things you can intervene with, which is really tough. In that general vein, you know, what are the governmental, institutional, and provider-level actions that are required to help clinicians do our best to do no financial harm, given the fact that we're prescribing really expensive drugs that require a lot of visits when caring for our patients with breast cancer in the curative and in the metastatic setting? Dr. Kamaria Lee: At the governmental level, there are patient assistant programs that do exist, and I think that those can continue and can become more robust. But I also think one element of those is oftentimes the programs that we have at the government level or even institutional levels might have a lot of paperwork or be harder for people with lower literacy levels to complete. And so I think the government can really try to make sure that the paperwork that is given, within reason, with all the information they need, but that the paperwork can be minimized and that there can be clear instructions, as well as increased health insurance options and, you know, medical debt forgiveness as more broad just overall interventions that are needed. I think additionally, institutions that have clinical trials can help ensure that enrollment can be at geographically diverse locations. Some trials do reimburse for travel costs, of course, but sometimes then patients need the reimbursement sooner than it comes. And so I think there's also those considerations of more so upfront funds for patients involved in clinical trials if they're going to have to travel far to be enrolled in that type of care or trying to, again, make clinical trials more available at diverse locations.  I would also say that it's important that those who design clinical trials use what is known as the “Common Sense Oncology” approach of making sure that they're designed in minimizing the use of outcomes that might have a smaller clinical benefit but may have a high financial toxicity. And that also goes to what providers can do, of understanding what's most important to a particular patient in front of them, what outcomes and what benefit, or you know, how many additional months of progression-free survival or things like that might be important to a particular patient and then also educating them and discussing what the associated financial burden is just so that they have the full picture as they make an informed decision. Dr. Hope Rugo: As much as we know. I mean, I think that that's one of the big challenges is that as we prescribe these expensive drugs and often require multiple visits, even, you know, really outside of the clinical trial setting, trying to balance the benefit versus the financial toxicity can be a huge challenge. And that's a big area, I think, that we still need help with, you know. As we have more drugs approved in the early-stage setting and treatments that could be expensive, oral medications, for example, in our Medicare population where the share of cost may be substantial upfront, you know, with an upfront cost, how do we balance the benefits versus the risk? And I think you make an important point that discussing this individually with patients after we found out what the cost is. I think warning patients about the potential for large out-of-pocket cost and asking them to contact us when they know is one way around this. You know, patients feeling like they're sort of out there with a prescription, a recommendation from their doctor, they're scared of their cancer, and they have this huge share of cost that we didn't know about. That's one challenge, and I don't know if there's any suggestions you have about how one should approach that communication with the patient. Dr. Kamaria Lee: Yes, I think part of it is truly looking at each patient as an individual and asking how much they want to know, right? So we all know that patients, some who want more information, some want less, and so I think one way to approach that is asking them about how much information do they want to know, what is most helpful to them. And then also, knowing that if you're in a well-resourced setting that does have the social workers and financial navigators, also making sure it's integrated in the multidisciplinary setting and so that they know who they can go to for what, but also know that as a clinician, you're always happy for them to bring up their concerns and that if it's something that you're not aware of, that you will connect them to the correct multidisciplinary team members who can accurately provide that additional information. Dr. Hope Rugo: Do you have any other additional comments that you'd like to mention that we haven't covered? I think the idea of a financial toxicity screen with two questions that could be implemented at change of therapy or just periodically throughout the course of treatment would be a really great thing, but I think we do need as much information on potential interventions as possible because that's really what challenges people. It's like finding out information that you can't handle. Your article provides a lot of strategies there, which I think are great and can be discussed on a practice and institutional level and applied. Dr. Kamaria Lee: Yeah, I would just like to thank you for the opportunity to discuss such an important topic within oncology and specifically for our patients with breast cancer. I agree that it can feel overwhelming, both for clinicians and patients, to navigate this topic that many of us are not as familiar with, but I would just say that the area of financial toxicity is continuing to evolve as we gather more information on most successful interventions and that our patients can often inform us on, you know, what interventions are most needed as we see them. And so you can have your thinking about it as you see individual patients of, "This person mentioned this could be more useful to them." And so I think also learning from our patients in this space that can seem overwhelming and that maybe we weren't all trained on in medical school to best understand how to approach it and how to give our patients the best care, not just medically, but also financially. Dr. Hope Rugo: Thank you, Dr. Lee, for sharing your insights with us today. Our listeners will find a link, as I mentioned earlier, to the Ed Book article we discussed today in the transcript of this episode. I think it's very useful, a useful resource, and not just for providers, but for clinic staff overall. I think this can be of great value and help open the discussion as well. Dr. Kamaria Lee: Thank you so much, Dr. Rugo. Dr. Hope Rugo: And thanks to our listeners for joining us today. Please join us again next month on By the Book for more insightful views on topics you'll be hearing at Education Sessions from ASCO meetings and our deep dives into new approaches that are shaping modern oncology. Thank you. 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. Hope Rugo  @hope.rugo  Dr. Kamaria Lee @ lee_kamaria Follow ASCO on social media:       @ASCO on X (formerly Twitter)       ASCO on Bluesky      ASCO on Facebook       ASCO on LinkedIn       Disclosures:      Dr. Hope Rugo:   Honoraria: Mylan/Viatris, Chugai Pharma  Consulting/Advisory Role: Napo Pharmaceuticals, Sanofi, Bristol Myer  Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Merck, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Hoffman La-Roche AG/Genentech, In., Stemline Therapeutics, Ambryx    Dr. Kamaria Lee: No relationships to disclose  

In der heutigen Folge sprechen die Finanzjournalisten Daniel Eckert und Holger Zschäpitz über enttäuschende Zahlen bei Münchener Rück, einen KI-Schocker von C3 AI und eine der besten Aktien auf dem deutschen Kurszettel. Außerdem geht es um Nordex, Nvidia, AMD, Gilead Sciences, The Trade Desk, Firefly Airospace, Rocket Lab US, Vaneck Space Innovators (WKN: A3DP9J), ARK Space Exploration & Innovation ETF (WKN: A3CUNY), Allianz, Apple, Berkshire Hathaway, Tesla, Rheinmetall. Wir freuen uns an Feedback über 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. Der Börsen-Podcast 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

Americká společnost Gilead Sciences, ve které je viceprezidentem český virolog a biochemik Tomáš Cihlář, před časem představila novou injekci na prevenci viru HIV. Slibuje účinnost vyšší než 99%, přičemž hlavní výhodou oproti dosavadním způsobům prevence je to, že její podání stačí jednou za šest měsíců. Lék už prošel Úřadem pro kontrolu potravin a léčiv (FDA), Světovou zdravotnickou organizací (WHO) a ke schválení ho na konci července doporučila i Evropská agentura pro léčivé přípravky (EMA). Co ještě musí následovat, aby se injekce dostala k pacientům? Na jakém principu funguje? A co by mohla znamenat pro celosvětový boj s virem HIV, kterým je podle odhadů nakažených více než 40 milionů lidí? I na to ve Výtahu Respektu odpovídá Martin Uhlíř.

HIV isn’t over — it’s just been ignored. Black women account for a disproportionate number of new cases, the South is ground zero, and the stigma is still killing us. Roland Martin, Dr. Toyin Nwafor, Raheem DeVaughn, and frontline organizers break the silence on a public health crisis America refuses to face. In response to this staggering trend, Gilead Sciences has launched the Setting the P.A.C.E. initiative. The Prevention, Arts and Advocacy, Community, and Education program is a three-year, $12.6 million commitment aimed at expanding HIV prevention efforts in underserved communities. Dr. Toyin Nwafor, Executive Director of Gilead U.S. HIV Medical Affairs, and Raheem DeVaughn, an award-winning musician and partner in the Gilead Setting the P.A.C.E. initiative.

In this episode, Kevin Kalinsky, MD, MS, FASCO, and Sara M. Tolaney, MD, MPH, discuss the most clinically relevant data in breast cancer presented at the 2025 ASCO Annual Meeting, including: DESTINY-Breast09: phase III trial of trastuzumab deruxtecan with or without pertuzumab vs THP as first-line treatment of HER2-positive advanced/metastatic breast cancerASCENT-04/KEYNOTE-D19: phase III trial of first-line sacituzumab govitecan plus pembrolizumab vs chemotherapy plus pembrolizumab in PD-L1–positive advanced TNBCSERENA-6: phase III trial of ctDNA-guided switch to camizestrant plus CDK4/6i vs continued AI plus CDK4/6i following ESR1 mutation emergence in HR-positive/HER2-negative advanced breast cancerINAVO120: OS from phase III study of first-line inavolisib/PBO plus palbociclib plus fulvestrant in PIK3CA-mutated, HR-positive/HER2-negative, endocrine-resistant advanced breast cancerPresenters:Kevin Kalinsky, MD, MS, FASCO​Professor of Medicine​Louisa and Rand Glenn Family Chair in Breast Cancer Research​Winship Cancer Institute​Emory UniversityAtlanta, Georgia​Sara M. Tolaney, MD, MPH​Chief, Breast Oncology​Dana-Farber Cancer Institute​Associate Professor of Medicine​Harvard Medical School​Boston, Massachusetts​Content based on an online CME program supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc, Gilead Sciences, Inc., Lilly, Novartis Pharmaceuticals Corporation, and Stemline Therapeutics, Inc.Link to full program: https://bit.ly/4lFS4BC

What does it really mean to be “the man”? In many Latino communities—and beyond—men are taught that having lots of sexual partners is proof of status, strength, and masculinity. In this special episode, Dramos unpacks that toxic message, sharing personal stories about chasing validation, peer pressure, and the role of machismo culture in shaping harmful expectations. He explores why this obsession with “numbers” can lead to dishonesty, emptiness, and broken trust, and why true masculinity means respect, empathy, and protecting the people you’re intimate with—including their sexual health. Dramos also gets real about what he’s learned from his own past, and why having tough, honest conversations is the foundation of healthy relationships and healthy sexuality. This episode is brought to you by Healthysexual from Gilead Sciences.See omnystudio.com/listener for privacy information.

Synopsis: Host Rahul Chaturvedi sits down with Jeremy Bender, CEO of Day One Biopharmaceuticals, to explore the bold mission of transforming pediatric oncology. From earning FDA approval for a groundbreaking brain cancer drug to building a culture rooted in execution and empathy, Jeremy shares lessons from big pharma and startups alike. He discusses how to lead through uncertainty, scale with discipline, and stay focused on delivering targeted therapies for underserved patients. They also dive into real-world data, AI's emerging role in clinical trial design, and why pediatric-first innovation could reshape the future of oncology. Biography: Jeremy Bender, Ph.D., M.B.A. has served as our Chief Executive Officer, President and a member of our board of directors since September 2020. Prior to joining Day One, Dr. Bender was Vice President of Corporate Development at Gilead Sciences, a pharmaceutical company, from March 2018 to September 2020. Prior to that, he was Chief Operating Officer of Tizona Therapeutics from July 2015 to March 2018 and Chief Business Officer of Sutro Biopharma, a biotechnology company specializing in cancer and autoimmune therapeutics, from October 2012 to July 2015. Prior to joining Sutro Biopharma, he was Vice President of Corporate Development at Allos Therapeutics, a biotechnology company focused on cancer treatments, from January 2006 to September 2012. Dr. Bender also sits on the board of Mereo BioPharma as an independent board member. He started his career in the life sciences practice at Boston Consulting Group, a management consulting company. Dr. Bender holds a B.S. in Biological Sciences from Stanford University, a Ph.D. in Microbiology and Immunology from the University of Colorado, and an M.B.A. from the MIT Sloan School of Management.

Tune in as Dr Daejin Adiboye, Vice President, Therapeutic Area Head, Solid Tumor Oncology, AbbVie, explores both the evolution of cancer care and his leadership style over the last two decades. Together, Daejin and Jade discuss the lessons from his time in the clinic that shaped who he is today, the move to precision medicine in oncology, his work with the Cancer Support Community in San Francisco and much more. A little more on EMJ GOLD's guest… Dr Daejin Abidoye serves as Vice President, Therapeutic Area Head for Solid Tumor Oncology at AbbVie. In this role, he is responsible for the clinical development of all assets in late oncology clinical development.  His career includes over 20 years of experience in oncology, cancer research and drug development. Prior to joining AbbVie, Daejin was the Therapeutic Area Lead for Oncology Development and Clinical Research at Gilead Sciences. He has also held various roles at Seattle Genetics and Roche-Genentech. Dr. Abidoye is a board-certified oncologist with a career in clinical practice at Scripps Health in Southern California. 

In this episode, host Ben Plumley, along with co-host Yvette Raphael, reports from the International AIDS Society Scientific Conference in Kigali, Rwanda. They discuss significant advancements in HIV prevention, particularly the recent FDA approval of Lenacapavir, with Dr. Alex Kintu from Gilead Sciences. The conversation covers the clinical journey and delivery mechanisms of Lenacapavir, its impact on young people and pregnant women, and the urgency of making this innovation widely accessible amidst funding challenges. The episode also highlights the critical role of community engagement and accountability boards in informing and driving HIV prevention strategies. Tune in for an in-depth look at the latest scientific and policy developments in the fight against HIV/AIDS. 00:00 Introduction and Welcome 00:37 Yvette's Stage Takeover Experience 01:33 Discussion on Gilead Sciences and HIV Prevention 02:15 Dr. Alex Kintu's Background and Role 03:33 FDA Approval and Next Steps for Lenacapavir 04:08 Global Access and Regulatory Processes 11:04 Understanding Lena Kavir and Its Importance 17:36 Challenges and Future of HIV Prevention 27:23 Community Engagement and Youth Involvement 34:33 Closing Remarks and Call to Action

Growing up in a Latino household, real conversations about sex often felt one-sided—or didn’t happen at all. In this special episode, Dramos opens up about how that silence made it harder to talk openly with friends and partners about sex, intimacy, and boundaries. He explores the fears and cultural pressures that make these talks intimidating, from worries about inexperience to the weight of tradition. Dramos also shares why learning to be vulnerable with peers and partners is so important for sexual health and building real trust. From navigating dating and safe sex to getting tested regularly, this episode breaks down why these “hard conversations” matter—and how having them can help protect yourself and others, emotionally and physically. This episode is brought to you by Healthysexual from Gilead Sciences.See omnystudio.com/listener for privacy information.

Governor Josh Shapiro says he wants to be sure Pennsylvania plays a key role in developing artificial intelligence, as well as providing the energy needed to support it. Speaking at an energy and A-I summit in Pittsburgh this week, Shapiro said the state's skilled workforce and natural gas reserves helped attract a $20 billion dollar investment in new data centers recently pledged by Amazon. A number of large-scale data center projects were announced across the state including a $15 billion project planned for the Carlisle area, a $6 billion project in the Lancaster area and a $5 billion project planned for York County. A nonprofit group that helps unemployed people stay in their homes is calling for state property reassessment laws to be updated. The lawsuit could affect property owners across the state. Another attempt is being made to eliminate local property taxes in Pennsylvania: This latest effort, in the form of an amendment to the state Constitution, is co-sponsored by state Senator Doug Mastriano of Franklin County. It would prohibit school districts from collecting property taxes beginning July first, 2029 and require the General Assembly to come up with another funding method for public schools. Some state lawmakers are taking another shot at legalizing adult cannabis use in Pennsylvania. Senators Daniel Laughlin and Sharif Street, as well as Representatives Emily Kinkead and Abby Major introduced bipartisan recreational cannabis bills just four days apart. Both bills incentivize minority, women and veteran-owned small businesses to open dispensaries across the state. Pennsylvania is one of 49 states sharing in a 20 million dollar settlement with drug maker Gilead Sciences. It stems from a lawsuit which accused Gilead of illegally providing financial and other incentives to medical personnel in exchange for promoting and prescribing its HIV medications. Danville-based Geisinger is eliminating nearly 100 Geisinger Health Plan positions as part of an "operational restructuring" amid financial challenges that include a $231 million operating loss last year. Four independent voters in Pennsylvania are asking the state Supreme Court to rule that the closed primary system violates the state constitution. They filed a lawsuit arguing that keeping independents out of primaries effectively denies them the right to vote in many districts where primaries determine the outcome. The 260th York State Fair kicks off Friday. and runs through the following weekend until Sunday, July 27th. Support WITF: https://www.witf.org/support/give-now/See omnystudio.com/listener for privacy information.

Drs. Hope Rugo, Sheri Brenner, and Mikolaj Slawkowski-Rode discuss the struggle that health care professionals experience when terminally ill patients are suffering and approaches to help clinicians understand and respond to suffering in a more patient-centered and therapeutic way. TRANSCRIPT Dr. Hope Rugo: Hello, and welcome to By the Book, a monthly podcast series from ASCO that features engaging conversations between editors and authors of the ASCO Educational Book.  I'm your host, Dr. Hope Rugo. I'm director of the Women's Cancers Program and division chief of breast medical oncology at the City of Hope Cancer Center, and I'm also the editor-in-chief of the Educational Book. On today's episode, we'll be exploring the complexities of grief and oncology and the struggle we experience as healthcare professionals when terminally ill patients are suffering. Our guests will discuss approaches to help clinicians understand and respond to suffering in a more patient-centered and therapeutic way, as outlined in their recently published article titled, “Oncology and Suffering: Strategies on Coping With Grief for Healthcare Professionals.” I'm delighted today to welcome Dr. Keri Brenner, a clinical associate professor of medicine, palliative care attending, and psychiatrist at Stanford University, and Dr. Mikołaj Sławkowski-Rode, a senior research fellow in philosophy in the Humanities Research Institute at the University of Buckingham, where he also serves as director of graduate research in p hilosophy. He is also a research fellow in philosophy at Blackfriars Hall at the University of Oxford and associate professor at the University of Warsaw.  Our full disclosures are available in the transcript of this episode. Dr. Brenner and Dr. Sławkowski-Rode, thanks for being on the podcast today. Dr. Keri Brenner: Great to be here, Dr. Rugo. Thank you so much for that kind introduction. Dr. Mikołaj Sławkowski-Rode: Thank you very much, Dr. Rugo. It's a pleasure and an honor. Dr. Hope Rugo: So I'm going to start with some questions for both of you. I'll start with Dr. Brenner. You've spoken and written about the concept of suffering when there is no cure. For oncologists, what does it mean to attune to suffering, not just disease? And how might this impact the way they show up in difficult conversations with patients? Dr. Keri Brenner: Suffering is something that's so omnipresent in the work of clinical oncology, and I like to begin by just thinking about what is suffering, because it's a word that we use so commonly, and yet, it's important to know what we're talking about. I think about the definition of Eric Cassell, who was a beloved mentor of mine for decades, and he defined suffering as the state of severe distress that's associated with events that threaten the intactness of a person. And my colleague here at Stanford, Tyler Tate, has been working on a definition of suffering that encompasses the experience of a gap between how things are versus how things ought to be. Both of these definitions really touch upon suffering in a person-centered way that's relational about one's identity, meaning, autonomy, and connectedness with others. So these definitions alone remind us that suffering calls for a person-centered response, not the patient as a pathology, but the panoramic view of who the patient is as a person and their lived reality of illness. And in this light, the therapeutic alliance becomes one of our most active ingredients in care. The therapeutic alliance is that collaborative, trusting bond as persons that we have between clinician and patient, and it's actually one of the most powerful predictors of meaningful outcomes in our care, especially in oncologic care.  You know, I'll never forget my first day of internship at Massachusetts General Hospital. A faculty lecturer shared this really sage insight with us that left this indelible mark. She shared, “As physicians and healers, your very self is the primary instrument of healing. Our being is the median of the medicine.” So, our very selves as embodied, relationally grounded people, that's the median of the medicine and the first most enduring medicine that we offer. That has really borne fruit in the evidence that we see around the therapeutic alliance. And we see this in oncologic care, that in advanced cancer, a strong alliance with one's oncologist truly improves a patient's quality of life, treatment adherence, emotional well-being, and even surpasses structured interventions like psychotherapeutic interventions. Dr. Hope Rugo: That's just incredibly helpful information and actually terminology as well, and I think the concept of suffering differs so much. Suffering comes in many shapes and forms, and I think you really have highlighted that. But many oncologists struggle with knowing what to do when patients are suffering but can't be fixed, and I think a lot of times that has to do with oncologists when patients have pain or shortness of breath or issues like that. There are obviously many ways people suffer. But I think what's really challenging is how clinicians understand suffering and what the best approaches to respond to suffering are in the best patient-centered and therapeutic way. Dr. Keri Brenner: I get that question a lot from my trainees in palliative care, not knowing what to do. And my first response is, this is about how to be, not about knowing what to do, but how to be. In our medical training, we're trained often how to think and treat, but rarely how to be, how to accompany others. And I often have this image that I tell my trainees of, instead of this hierarchical approach of a fix-it mentality of all we're going to do, when it comes to elements of unavoidable loss, mortality, unavoidable sufferings, I imagine something more like accompaniment, a patient walking through some dark caverns, and I am accompanying them, trying to walk beside them, shining a light as a guide throughout that darkness. So it's a spirit of being and walking with. And it's so tempting in medicine to either avoid the suffering altogether or potentially overidentify with it, where the suffering just becomes so all-consuming like it's our own. And we're taught to instead strike a balance of authentic accompaniment through it. I often teach this key concept in my palli-psych work with my team about formulation. Formulation is a working hypothesis. It's taking a step back and asking, “Why? Why is this patient behaving in this manner? What might the patient's core inner struggle be?” Because asking that “why” and understanding the nuanced dimensions of a patient's core inner struggle will really help guide our therapeutic interactions and guide the way that we accompany them and where we choose to shine that light as we're walking with them. And oftentimes people think, “Well Keri, that sounds so sappy or oversentimental,” and it's not. You know, I'm just thinking about a case that I had a couple months ago, and it was a 28-year-old man with gastric cancer, metastatic disease, and that 28-year-old man, he was actually a college Division I athlete, and his dad was an acclaimed Division I coach. And our typical open-ended palliative care questions, that approach, infuriated them. They needed to know that I was showing up confident, competent, and that I was ready, on my A-game, with a real plan for them to follow through. And so my formulation about them was they needed somebody to show up with that confidence and competence, like the Division I athletes that they were, to really meet them and accompany them where they were on how they were going to walk through that experience of illness. Dr. Hope Rugo: These kinds of insights are so helpful to think about how we manage something that we face every day in oncology care. And I think that there are many ways to manage this.  Maybe I'll ask Dr. Sławkowski-Rode one question just that I think sequences nicely with what you're talking about.  A lot of our patients are trying to think about sort of the bigger picture and how that might help clinicians understand and support patients. So, the whole concept of spirituality, you know, how can we really use that as oncology clinicians to better understand and support patients with advanced illness, and how can that help patients themselves? And we'll talk about that in two different ways, but we'll just start with this broader question. Dr. Mikołaj Sławkowski-Rode: I think spirituality, and here, I usually refer to spirituality in terms of religious belief. Most people in the world are religious believers, and it is very intuitive and natural that religious beliefs would be a resource that people who help patients with a terminal diagnosis and healthcare professionals who work with those patients appeal to when they try to help them deal with the trauma and the stress of these situations.  Now, I think that the interesting thing there is that very often the benefit of appealing to a religious belief is misunderstood in terms of what it delivers. And there are many, many studies on how religious belief can be used to support therapy and to support patients in getting through the experience of suffering and defeating cancer or facing a terminal diagnosis. There's a wealth of literature on this. But most of the literature focuses on this idea that by appealing to religious belief, we help patients and healthcare practitioners who are working with them get over the fact and that there's a terminal diagnosis determining the course of someone's life and get on with our lives and engaging with whatever other pursuits we might have, with our job if we're healthcare practitioners, and with the other things that we might be passionate about in our lives. And the idea here is that this is what religion allows us to do because we sort of defer the need to worry about what's going to happen to us until the afterlife or some perspective beyond the horizon of our life here.  However, my view is – I have worked beyond philosophy also with theologians from many traditions, and my view here is that religion is something that does allow us to get on with our life but not because we're able to move on or move past the concerns that are being threatened by illness or death, but by forming stronger bonds with these things that we value in our life in a way and to have a sense of hope that these will be things that we will be able to keep an attachment to despite the threat to our life. So, in a sense, I think very many approaches in the field have the benefit of religion upside down, as it were, when it comes to helping patients and healthcare professionals who are engaged with their illness and treating it. Dr. Hope Rugo: You know, it's really interesting the points that you make, and I think really important, but, you know, sometimes the oncologists are really struggling with their own emotional reactions, how they are reacting to patients, and dealing with sort of taking on the burden, which, Dr. Brenner, you were mentioning earlier. How can oncologists be aware of their own emotional reactions? You know, they're struggling with this patient who they're very attached to who's dying or whatever the situation is, but you want to avoid burnout as an oncologist but also understand the patient's inner world and support them. Dr. Keri Brenner: I believe that these affective, emotional states, they're contagious. As we accompany patients through these tragic losses, it's very normal and expected that we ourselves will experience that full range of the human experience as we accompany the patients. And so the more that we can recognize that this is a normative dimension of our work, to have a nonjudgmental stance about the whole panoramic set of emotions that we'll experience as we accompany patients with curiosity and openness about that, the more sustainable the work will become. And I often think about the concept of countertransference given to us by Sigmund Freud over 100 years ago. Countertransference is the clinician's response to the patient, the thoughts, feelings, associations that come up within us, shaped by our own history, our own life events, those unconscious processes that come to the foreground as we are accompanying patients with illness. And that is a natural part of the human experience. Historically, countertransference was viewed as something negative, and now it's actually seen as a key that can unlock and enlighten the formulation about what might be going on within the patient themselves even. You know, I was with a patient a couple weeks ago, and I found myself feeling pretty helpless and hopeless in the encounter as I was trying to care for them. And I recognized that countertransference within myself that I was feeling demoralized. It was a prompt for me to take a step back, get on the balcony, and be curious about that because I normally don't feel helpless and hopeless caring for my patients. Well, ultimately, I discovered through processing it with my interdisciplinary team that the patient likely had demoralization as a clinical syndrome, and so it's natural many of us were feeling helpless and hopeless also accompanying them with their care. And it allowed us to have a greater interdisciplinary approach and a more therapeutic response and deeper empathy for the patient's plight. And we can really be curious about our countertransferences. You know, a few months ago, I was feeling bored and distracted in a family meeting, which is quite atypical for me when I'm sharing serious illness news. And it was actually a key that allowed me to recognize that the patient was trying to distract all of us talking about inconsequential facts and details rather than the gravitas of her illness.  Being curious about these affective states really allows us to have greater sustainability within our own practice because it normalizes that human spectrum of emotions and also allows us to reduce unconscious bias and have greater inclusivity with our practice because what Freud also said is that what we can't recognize and say within our own selves, if we don't have that self-reflective capacity, it will come out in what we do. So really recognizing and having the self-awareness and naming some of these emotions with trusted colleagues or even within our own selves allows us to ensure that it doesn't come out in aberrant behaviors like avoiding the patient, staving off that patient till the end of the day, or overtreating, offering more chemotherapy or not having the goals of care, doing everything possible when we know that that might result in medically ineffective care. Dr. Hope Rugo: Yeah, I love the comments that you made, sort of weaving in Freud, but also, I think the importance of talking to colleagues and to sharing some of these issues because I do think that oncologists suffer from the fact that no one else in your life wants to hear about dying people. They don't really want to hear about the tragic cases either. So, I think that using your community, your oncology community and greater community within medicine, is an important part of being able to sort of process. Dr. Keri Brenner: Yes, and Dr. Rugo, this came up in our ASCO [Education] Session. I'd love to double click into some of those ways that we can do this that aren't too time consuming in our everyday practice. You know, within palliative care, we have interdisciplinary rounds where we process complex cases. Some of us do case supervision with a trusted mentor or colleague where we bring complex cases to them. My team and I offer process rounds virtually where we go through countertransference, formulation, and therapeutic responses on some tough cases.  You know, on a personal note, just last week when I left a family meeting feeling really depleted and stuck, I called one of my trusted colleagues and just for 3 minutes constructively, sort of cathartically vented what was coming up within me after that family meeting, which allowed me to have more of an enlightened stance on what to do next and how to be therapeutically helpful for the case. One of my colleagues calls this "friend-tors." They coined the phrase, and they actually wrote a paper about it. Who within your peer group of trusted colleagues can you utilize and phone in real time or have process opportunities with to get a pulse check on where what's coming up within us as we're doing this work? Dr. Hope Rugo: Yeah, and it's an interesting question about how one does that and, you know, maintaining that as you move institutions or change places or become more senior, it's really important.  One of the, I think, the challenges sometimes is that we come from different places from our patients, and that can be an issue, I think when our patients are very religious and the provider is not, or the reverse, patients who don't have religious beliefs and you're trying to sort of focus on the spirituality, but it doesn't really ring true. So, Dr. Sławkowski-Rode, what resources can patients and practitioners draw on when they're facing death and loss in the absence of, or just different religious beliefs that don't fit into the standard model? Dr. Mikołaj Sławkowski-Rode: You're absolutely right that this can be an extremely problematic situation to be in when there is that disconnect of religious belief or more generally spiritual engagement with the situation that we're in. But I just wanted to tie into what Dr. Brenner was saying just before. I couldn't agree more, and I think that a lot of healthcare practitioners, oncologists in particular who I've had the pleasure to talk to at ASCO and at other events as well, are very often quite skeptical about emotional engagement in their profession. They feel as though this is something to be managed, as it were, and something that gets in the way. And they can often be very critical of methods that help them understand the emotions and extend them towards patients because they feel that this will be an obstacle to doing their job and potentially an obstacle also to helping patients to their full ability if they focus on their own emotions or the burden that emotionally, spiritually, and in other ways the illness is for the patient. They feel that they should be focusing on the cancer rather than on the patient's emotions. And I think that a useful comparison, although, you know, perhaps slightly drastic, is that of combat experience of soldiers. They also need to be up and running and can't be too emotionally invested in the situation that they're in. But there's a crucial difference, which is that soldiers are usually engaged in very short bursts of activity with the time to go back and rethink, and they often have a lot of support for this in between. Whereas doctors are in a profession where their exposure to the emotions of patients and their own emotions, the emotions of families of patients is constant. And I think that there's a great danger in thinking that this is something to be avoided and something to compartmentalize in order to avoid burnout. I think, in a way, burnout is more sure to happen if your emotions and your attachment to your patients goes ignored for too long. So that's just following up on Keri's absolutely excellent points. As far as the disconnect is concerned, that's, in fact, an area in which I'm particularly interested in. That's where my research comes in. I'm interested in the kinds of connections that we have with other people, especially in terms of maintaining bonds when there is no spiritual belief, no spiritual backdrop to support this connection. In most religious traditions, we have the framework of the religious belief that tells us that the person who we've lost or the values that have become undermined in our life are something that hasn't been destroyed permanently but something that we can still believe we have a deep connection to despite its absence from our life. And how do you rebuild that sense of the existence of the things that you have perceivably lost without the appeal to some sort of transcendent realm which is defined by a given religion? And that is a hard question. That's a question, I think, that can be answered partly by psychology but also partly by philosophy in terms of looking at who we are as human beings and our nature as people who are essentially, or as entities that are essentially connected to one another. That connection, I believe, is more direct than the mediation of religion might at first suggest. I think that we essentially share the world not only physically, it's not just the case that we're all here, but more importantly, the world that we live in is not just the physical world but the world of meanings and values that helps us orient ourselves in society and amongst one another as friends and foes. And it is that shared sense of the world that we can appeal to when we're thinking about retaining the value or retaining the connection with the people who we have lost or the people who are helping through, go through an experience of facing death. And just to finish, there's a very interesting question, I think, something that we possibly don't have time to explore, about the degree of connection that we have with other people. So, what I've just been saying is something that rings more true or is more intuitive when we think about the connections that we have to our closest ones. We share a similar outlook onto the world, and our preferences and our moods and our emotions and our values are shaped by life with the other person. And so, appealing to these values can give us a sense of a continued presence. But what in those relationships where the connection isn't that close? For example, given the topic of this podcast, the connection that a patient has with their doctor and vice versa. In what sense can we talk about a shared world of experience? Well, I think, obviously, we should admit degrees to the kind of relationship that can sustain our connection with another person. But at the same time, I don't think there's a clear cutoff point. And I think part of emotional engagement in medical practice is finding yourself somewhere on that spectrum rather than thinking you're completely off of it. That's what I would say. Dr. Hope Rugo: That's very helpful and I think a very helpful way of thinking about how to manage this challenging situation for all of us.  One of the things that really, I think, is a big question for all of us throughout our careers, is when to address the dying process and how to do that. Dr. Brenner, you know, I still struggle with this – what to do when patients refuse to discuss end-of-life but they're very close to end of life? They don't want to talk about it. It's very stressful for all of us, even where you're going to be, how you're going to manage this. They're just absolutely opposed to that discussion. How should we approach those kinds of discussions? How do we manage that? How do you address the code discussion, which is so important? You know, these patients are not able to stay at home at end-of-life in general, so you really do need to have a code discussion before you're admitting them. It actually ends up being kind of a challenge and a mess all around. You know, I would love your advice about how to manage those situations. Dr. Keri Brenner: I think that's one of the most piercing and relevant inquiries we have within our clinical work and challenges. I often think of denial not as an all-or-nothing concept but rather as parts of self. There's a part of everyone's being where the unconscious believes it's immortal and will live on forever, and yet we all know intellectually that we all have mortality and finitude and transience, and that time will end. We often think of this work as more iterative and gradual and exposure based. There's potency to words. Saying, “You are dying within days,” is a lot higher potency of a phrase to share than, “This is serious illness. This illness is incurable. Time might be shorter than we hoped.” And so the earlier and more upstream we begin to have these conversations, even in small, subtle ways, it starts to begin to expose the patient to the concept so they can go from the head to the heart, not only knowing their prognosis intellectually but also affectively, to integrate it into who they are as a person because all patients are trying to live well while also we're gradually exposing them to this awareness of mortality within their own lived experience of illness. And that, ideally, happens gradually over time. Now, there are moments where the medical frame is very limited, and we might have short days, and we have to uptitrate those words and really accompany them more radically through those high-affective moments. And that's when we have to take a lot of more nuanced approaches, but I would say the more earlier and upstream the better. And then the second piece to that question as well is coping with our own mortality. The more we can be comfortable with our own transience and finitude and limitations, the more we will be able to accompany others through that. And even within my own life, I've had to integrate losses in a way where before I go in to talk to one of my own palliative care patients, one mantra I often say to myself is, “I'm just a few steps behind you. I don't know if it's going to be 30 days or 30 years, but I'm just a few steps behind you on this finite, transient road of life that is the human experience.” And that creates a stance of accompaniment that patients really can experience as they're traversing these tragedies. Dr. Hope Rugo: That's great. And I think those are really important points and actually some pearls, which I think we can take into the clinic. I think being really concrete when really the expected life expectancy is a few days to a couple of weeks can be very, very helpful. And making sure the patients hear you, but also continuing to let them know that, as oncologists, we're here for them. We're not abandoning them. I think that's a big worry for many, certainly of my patients, is that somehow when they would go to hospice or be a ‘no code', that we're not going to support them anymore or treat them anymore. That is a really important process of that as well. And of course, engaging the team makes a big difference because the whole oncology team can help to manage situations that are particularly challenging like that. And just as we close, I wanted to ask one last question of you, Dr. Brenner, that suffering, grief, and burnout, you've really made the point that these are not problems to fix but dimensions that we want to attend to and acknowledge as part of our lives, the dying process is part of all of our lives. It's just dealing with this in the unexpected and the, I think, unpredictability of life, you know, that people take on a lot of guilt and all sorts of things about, all sorts of emotions. And the question is now, people have listened to this podcast, what can they take back to their oncology teams to build a culture that supports clinicians and their team at large to engage with these realities in a meaningful and sustainable way? I really feel like if we could build the whole team approach where we're supporting each other and supporting the patients together, that that will help this process immeasurably. Dr. Keri Brenner: Yes, and I'm thinking about Dr. Sławkowski-Rode's observation about the combat analogy, and it made me recognize this distinction between suppression and repression. Repression is this unconscious process, and this is what we're taught to do in medical training all the time, to just involuntarily shove that tragedy under the rug, just forget about it and see the next patient and move on. And we know that if we keep unconsciously shoving things under the rug, that it will lead to burnout and lack of sustainability for our clinical teams. Suppression is a more conscious process. That deliberate effort to say, “This was a tragedy that I bore witness to. I know I need to put that in a box on the shelf for now because I have 10 other patients I have to see.” And yet, do I work in a culture where I can take that off the shelf during particular moments and process it with my interdisciplinary team, phone a friend, talk to a trusted colleague, have some trusted case supervision around it, or process rounds around it, talk to my social worker? And I think the more that we model this type of self-reflective capacity as attendings, folks who have been in the field for decades, the more we create that ethos and culture that is sustainable because clinician self-reflection is never a weakness, rather it's a silent strength. Clinician self-reflection is this portal for wisdom, connectedness, sustainability, and ultimately transformative growth within ourselves. Dr. Hope Rugo: That's such a great point, and I think this whole discussion has been so helpful for me and I hope for our audience that we really can take these points and bring them to our practice. I think, “Wow, this is such a great conversation. I'd like to have the team as a whole listen to this as ways to sort of strategize talking about the process, our patients, and being supportive as a team, understanding how we manage spirituality when it connects and when it doesn't.” All of these points, they're bringing in how we process these issues and the whole idea of suppressing versus sort of deciding that it never happened at all is, I think, very important because that's just a tool for managing our daily lives, our busy clinics, and everything we manage. Dr. Keri Brenner: And Dr. Rugo, it's reminding me at Stanford, you know, we have this weekly practice that's just a ritual where every Friday morning for 30 minutes, our social worker leads a process rounds with us as a team, where we talk about how the work that we're doing clinically is affecting us in our lives in ways that have joy and greater meaning and connectedness and other ways that might be depleting. And that kind of authentic vulnerability with one another allows us to show up more authentically for our patients. So those rituals, that small 30 minutes once a week, goes a long way. And it reminds me that sometimes slowing things down with those rituals can really get us to more meaningful, transformative places ultimately. Dr. Hope Rugo: It's a great idea, and I think, you know, making time for that in everybody's busy days where they just don't have any time anymore is important. And you don't have to do it weekly, you could even do something monthly. I think there's a lot of options, and that's a great suggestion. I want to thank you both for taking your time out for this enriching and incredibly helpful conversation. Our listeners will find a link to the Ed Book article we discussed today, which is excellent, in the transcript of this episode. I want to thank you again, Dr. Brenner and Dr. Sławkowski-Rode, for your time and for your excellent thoughts and advice and direction. Dr. Mikołaj Sławkowski-Rode: Thank you very much, Dr. Rugo. Dr. Keri Brenner: Thank you. Dr. Hope Rugo: And thanks to our listeners for joining us today. Please join us again next month on By the Book for more insightful views on topics you'll be hearing at the education sessions from ASCO meetings and our deep dives on new approaches that are shaping modern oncology. 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. Hope Rugo @hope.rugo Dr. Keri Brenner @keri_brenner Dr. Mikolaj Slawkowski-Rode @MikolajRode Follow ASCO on social media:      @ASCO on X (formerly Twitter)      ASCO on Bluesky     ASCO on Facebook      ASCO on LinkedIn      Disclosures:     Dr. Hope Rugo: Honoraria: Mylan/Viatris, Chugai Pharma Consulting/Advisory Role: Napo Pharmaceuticals, Sanofi, Bristol Myer Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Merck, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Hoffman La-Roche AG/Genentech, In., Stemline Therapeutics, Ambryx Dr. Keri Brenner: No relationships to disclose Dr. Mikolaj Slawkowski-Rode: No relationships to disclose    

Cultural taboos around sex and sexuality run deep in many Latino households, often shutting down important conversations before they even start. In this special episode, Dramos opens up about how religion, gender roles, and family expectations shaped his own understanding of sexual health—or lack of it. He explores how these cultural norms can leave young people unprepared, misinformed, and anxious about their own well-being. Plus, Dramos shares what he wishes he'd learned growing up, why sexual health is about so much more than just sex, and how we can start having the hard conversations to better support the next generation. This episode is brought to you by Healthysexual from Gilead Sciences.See omnystudio.com/listener for privacy information.

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

In this podcast, expert faculty, Dr Stuart Gordon and Dr Nancy Reau discuss an illustrative patient case to demonstrate how they individualize primary biliary cholangitis (PBC) therapy for patients ​with cirrhosis. Topics covered include:AASLD guideline recommendations for second-line therapy for PBCConsiderations when using newer agents for second-line treatment of PBC in patients with cirrhosis: elafibranor and seladelparPresenters:Stuart C. Gordon, MD Professor of MedicineWayne State University School of MedicineDirector, Division of HepatologyHenry Ford HealthDetroit, MichiganNancy Reau, MD Professor of MedicineRichard B. Capps Chair of HepatologyChief, Section of HepatologyAssociate Director, Solid Organ TransplantationRush University Medical CenterChicago, IllinoisTo learn more about PBC management, check out our program, Curbside Consults: Expert Insights on Challenges in PBC Management.Supported by educational grants from Gilead Sciences, Inc. and Ipsen Biopharmaceuticals, Inc

In this podcast, expert faculty, Dr Stuart Gordon and Dr Nancy Reau, use an illustrative patient case to explore the roles of ALP and other biochemical markers in PBC management, and explain what to expect from treatment. Topics covered include: How baseline ALP can affect ALP normalization after second-line treatment with elafibranor and seladelparPotential outcomes if ALP normalization cannot be achievedThe importance of managing fatigue, pruritus, and sleep disturbances independently of the biochemical responsePresenters:Stuart C. Gordon, MDProfessor of MedicineWayne State University School of MedicineDirector, Division of HepatologyHenry Ford HealthDetroit, MichiganNancy Reau, MDProfessor of MedicineRichard B. Capps Chair of HepatologyChief, Section of HepatologyAssociate Director, Solid Organ TransplantationRush University Medical CenterChicago, IllinoisTo learn more about PBC management, check out our program, Curbside Consults: Expert Insights on Challenges in PBC Management. Supported by educational grants from Gilead Sciences, Inc. and Ipsen Biopharmaceuticals, Inc

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

In this podcast, listen as experts Alan Bonder, MD, AGAF, and Aparna Goel, MD, discuss how they assess the symptoms of primary biliary cholangitis (PBC) and explore how new therapeutic agents may help alleviate symptom burden. Topics include:Strategies and tools for assessing pruritusNonpharmacologic and pharmacologic management of pruritusSecond-line agents and their impact on pruritusInvestigational treatments for pruritusPresenters:Alan Bonder, MD, AGAFAssociate Professor of MedicineMedical Director of Liver TransplantDepartment of GastroenterologyBeth Israel Deaconess Medical CenterHarvard Medical SchoolBoston, MassachusettsAparna Goel, MDAssociate Clinical Professor of MedicineDivision of Gastroenterology and HepatologyStanford UniversityPalo Alto, CaliforniaContent based on an online CME program supported by independent educational grants from Gilead Sciences, Inc., and Ipsen Biopharmaceuticals, Inc​.To learn more about PBC management, check out our program, Curbside Consults: Expert Insights on Challenges in PBC Management.

How do you decide when to move from first-line to second-line treatment for primary biliary cholangitis (PBC)? In this podcast, listen as experts Alan Bonder, MD, AGAF, and Aparna Goel, MD, discuss this question and more, including:How and when to measure treatment responseEvidence-based goals of therapyConsiderations for second-line treatmentNew agents for second-line treatment: PPAR agonistsPresenters:Alan Bonder, MD, AGAFAssociate Professor of MedicineMedical Director of Liver TransplantDepartment of GastroenterologyBeth Israel Deaconess Medical CenterHarvard Medical SchoolBoston, MassachusettsAparna Goel, MDAssociate Clinical Professor of MedicineDivision of Gastroenterology and HepatologyStanford UniversityPalo Alto, CaliforniaContent based on an online CME program supported by independent educational grants from Gilead Sciences, Inc., and Ipsen Biopharmaceuticals, Inc​.To learn more about PBC management, check out our program, Curbside Consults: Expert Insights on Challenges in PBC Management.Supported by educational grants from Gilead Sciences, Inc. and Ipsen Biopharmaceuticals, Inc