Podcasts about Plenary session

JD Greear delivers Session One from our EDM Conference, urging campus ministries and churches to focus on multiplication by equipping every believer to embrace their role in evangelism, discipleship, and missions.

Shavuot Tikkun Plenary session with Sarah Hurwitz, in Hevruta with Tom Fields-Meyer, in discussion of her new book: “As a Jew: Reclaiming our Story from Those who Blame, Shame and Try to Erase Us,” at Temple Beth Am, Los Angeles, June 1, 2025. Introduced by Rabbi Rebecca Schatz. (Youtube) Special Guests: Sarah Hurwitz and Tom Fields-Meyer.

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

In this episode, John Musyimi delivers a talk on maintaining the authority of the Bible over pragmatism. He delves into the fear of God versus the allure of success, exploring various temptations that can lead us towards pragmatism. John is a member of our network and the Lead Pastor of North Point Baptist Church in Nairobi, Kenya. This talk was originally given at the 2024 Pillar Unite Conference.

Audio from our 2024 Shepherds Conference: Unity—Fighting Schism for the Good of the Church. October 4, 2024PLENARY SESSION 2 | JUDE: BUILDING UNITYRev. Jeremy Vander GalienJude teaches us practical ways to build unity while fighting divisiveness. How are pastors called to strengthen their congregations in faith and love? What encouragement does God give us in this difficult work?Jeremy has been the senior pastor at Pine Grove Community Church in Rhinelander, WI, since 2015. He co-founded Armis Dei Academy, a Christian classical school, in 2021. He's been married to Mandi since 2000, and they have eight children and four grandchildren.For more information on New Geneva Academy's pastoral training program visit our website: www.newgenevaacademy.comNGA email sign-up ★ Support this podcast ★

Audio from our 2024 Shepherds Conference: Unity—Fighting Schism for the Good of the Church. October 3, 2024 PLENARY SESSION 1 | JUDE: DEALING WITH THOSE WHO DIVIDERev. Jeremy Vander GalienJude spends more than half his short book warning against those who follow "the way of Cain," sowing discord among brothers. How do pastors guard their congregations against these men? And given our own divisive hearts, how do we keep ourselves from the sin of schism?Jeremy has been the senior pastor at Pine Grove Community Church in Rhinelander, WI, since 2015. He co-founded Armis Dei Academy, a Christian classical school, in 2021. He's been married to Mandi since 2000, and they have eight children and four grandchildren.For more information on New Geneva Academy's pastoral training program visit our website: www.newgenevaacademy.comNGA email sign-up ★ Support this podcast ★

In this episode, Nate Akin gives a talk on Sola Scriptura, biblical authority, tradition, and how baptists have navigated these topics. This talk was originally given at the 2024 Pillar Unite Conference.

Check out the latest QuadCast where we interview Jason Efstathiou at the 2024 ASTRO Annual Meeting about his Plenary Session on the PARTIQoL trial, which is a first of its kind randomized trial of IMRT vs. Proton Therapy for localized prostate cancer. Don't miss it. @QuadShotNews@drjefstathiou@HarvardRadOnc@SamuelMarcromMD Check out the website and subscribe to the newsletter! www.quadshotnews.com Founders & Lead Authors: Laura Dover & Caleb Dulaney Podcast Host: Sam Marcrom

Juliette Gash reports ahead of the first plenary session of the European Parliament will take place in Strasbourg.

Drs. John Sweetenham and Angela DeMichele discuss potentially ground-breaking abstracts in breast and lung cancer as well as notable research on artificial intelligence and its impact on cancer care, all of which were featured at the 2024 ASCO Annual Meeting.  TRANSCRIPT Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham from UT Southwestern's Harold C. Simmons Comprehensive Cancer Center and host of the ASCO Daily News Podcast. My guest today is Dr. Angela DeMichele, the Marianne and Robert McDonald Professor in Breast Cancer Research and co-leader of the Breast Cancer Program at the University of Pennsylvania's Abramson Cancer Center. Dr. DeMichele also served as the chair of the 2024 ASCO Annual Meeting Scientific Program. Today, she'll be sharing her reflections on the Annual Meeting and we'll be highlighting some advances and innovations that are addressing unmet needs and accelerating progress in oncology.  Our full disclosures are available in the transcript of this episode.  Dr. DeMichele, congratulations on a very robust and highly successful program at ASCO24, and thanks for joining us on the podcast today. Dr. Angela DeMichele: Well, thanks so much for having me, Dr. Sweetenham. It's a pleasure to be here.  Dr. John Sweetenham: The presidential theme of the Annual Meeting this year was the "The Art and Science of Cancer Care: From Comfort to Cure." And this was certainly reflected throughout the meeting in Chicago that welcomed more than 40,000 attendees from across the globe. I know our listeners will be interested to hear some of your own reflections from the meeting now that we're on the other side of it, so to spea  Dr. Angela DeMichele: Yes. Well, I will say that playing this role in the annual meeting really was a highlight of my career, and I feel so fortunate to have had the opportunity to do it. We had over 200 sessions, and in many, if not all of these sessions, we really tried to make sure that there was a case that really sort of grounded the session to really help people understand: you're going to hear about science, but how are you going to apply that? Who is the patient for whom this science really is important?  We had over 7,000 abstracts submitted, and our 25 tracks and their chairs really pulled through to find really the best science that we could present this year. I think what you saw really was a representation of that across the board: incredible advances in lung cancer, breast cancer, melanoma, GI cancers; also really cutting-edge technologies: AI, as we'll talk about in a little while circulating markers like ctDNA, new drug development, new classes of drugs. So it was really an exciting meeting. I mean, some highlights for me, I would say, were certainly the Plenary, and we can talk a little bit about that. Also, we had a fantastic ASCO/AACR Joint Session on “Drugging the “Undruggable Target: Successes, Challenges, and the Road Ahead.” And, if any of the listeners have not had a chance to hear this, it's really worth going in and watching this because it really brought together three amazing speakers who talked about the successes in KRAS, and then really, how are we using that success in learning how to target KRAS to now targeting a variety of other previously thought to be undruggable targets. I learned so much. And there's really both the academic and the pharma perspective there. So I'd really encourage watching this session. The other session that I really thought was terrific was one that I was honored to chair, which was a fireside chat (“How and Where Will Public Investment Accelerate Progress in Oncology? A Discussion with the NIH and NCI Directors”) with both Dr. Monica Bertagnolli, who is the director of the NIH, and Dr. Kim Rathmell, who's now the director of the NCI. And boy, I'll tell you, these two incredibly smart, thoughtful, insightful women; it was a great conversation. They were really understanding of the challenges we face conducting research, practicing medicine. And maybe different from leadership at the NIH in the past, they've really taken the approach to say that everything they do is focused on the patient, and they don't limit themselves to just research or just science, that everything that the NIH does, and particularly the NCI does, really has to be focused on making sure we can give patients the best possible care. And I think they're being very thoughtful about building important infrastructure that's going to take us into the future, incorporating AI, incorporating new clinical trial approaches that are going to make it faster and easier to conduct clinical trials and to get the results that we need sooner. So just a few of the highlights, I think, from some really interesting sessions. Dr. John Sweetenham: It certainly was an extremely enriching and impactful ASCO24. And I think that the overall theme of the meeting was extremely well reflected in the content with this amazing mix of really, truly impactful science, along with a great deal of patient-centered healthcare delivery science to accompany it. So, I completely agree with you about that. There was a lot, of course, to take in over the five days of the meeting, but I'm sure that our listeners would be very interested to hear about one or two abstracts that really stood out for you this year.  Dr. Angela DeMichele: Sure. I'm a breast cancer specialist, so I can't help but feel that the late breaking abstract, the DESTINY-Breast06 trial, was really important for the field of breast cancer. So just briefly, this is a study of the antibody drug conjugate T-DxD, trastuzumab deruxtecan. This is a drug that is actually now approved in metastatic breast cancer, really effective in HER2-positive disease. But the question that this trial was trying to answer is, can this drug, which is built with the herceptin antibody against HER2, then linked to a chemotherapeutic molecule, can this work even in the setting of very, very low HER2 expression on a tumor? I think this is an incredibly important question in the field of antibody drug conjugates, of which there are now many across diseases, is how much of the target do you really need to have on the surface of the tumor?  We had seen previously HER2 overexpressing tumors respond really well to this drug. HER2 tumors that have an intermediate level of expression were tested in the DP04 trial, and we saw that even those 2+ intermediate tumors responded well to this drug. The DP06 trial that was presented at ASCO was looking at this group of patients that have even less HER2 on the surface. So we typically measure HER2 by immunohistochemistry as 0, 1+, 2+, or 3+. And this was looking at patients whose tumors were over 0, but were at 1+ or below, so low and ultra-low. And it turned out that compared to treatment of physician's choice, the drug really had quite a lot of activity, even in these patients who have very little HER2 on their tumors, really showing progression-free survival benefits in the HER2-low and HER2-ultra-low groups that were appreciable on the order of about 5 months, additional progression free survival hazard ratios around 0.6, so really demonstrating that utilizing an antibody drug conjugate, where you've got very little target, can still be a way to get that drug to a tumor.   And I think it'll remain to be seen whether other ADCs can have activity at very low levels of IHC expression of whatever target they're designed against. I think one of the tricky things here for implementing this in breast cancer will be how do pathologists actually identify the tumors that are ultra-low because it's not something that we typically do. And so we'll go through a period, I think, of adjustment here of really trying to understand how to measure this. And there are a bunch of new technologies that I think will do a better job of detecting low levels of the protein on the surface of the tumor because the current IHC test really isn't designed to do that. It was only designed to be focused on finding the tumors that had high levels. So we have some newer technologies with immunofluorescence, for example, that can really get down to very low levels. And I think this is going to be a whole new area of ADCs, target detection – how low can you go to still see activity? So I thought that this was an important abstract for many reasons.  I will just say the second area that I was really particularly impressed with and had a big impact on me were the two lung cancer abstracts that were presented in the Plenary, the LAURA trial (LBA4) and the ADRIATIC trial (LBA5). And I think, I've been in the field of oncology for 30 years now, and when I started in the late ‘90s, lung cancer was a disease for which we had very few treatments. If we didn't catch it early and surgery wasn't possible for non-small cell lung cancer, really, it was a horrible prognosis. So we knew this year was the 20th anniversary of the discovery of EGFR as a subtype of lung cancer. That was really, I think, a turning point in the field of non-small cell lung cancer – finding a target. And now seeing the LAURA trial show that osimertinib really had such an enormous impact on progression-free survival amongst these patients who had EGFR-positive non-small cell lung cancer, progression-free survival hazard ratio of 0.16; there was a standing ovation.  And one of the really big privileges of being the Scientific Program Chair is getting to moderate the Plenary Session, and it's a really amazing experience to be standing up there or sitting there while the presenter is getting a standing ovation. But this was well deserved because of the impact this is having on patients with EGFR positive lung cancer. And it was similar with the ADRIATIC trial, which looked at the benefits of adding immunotherapy in limited-stage small-cell lung cancer. Again, a disease that treatment has not changed in 30 years, and so the addition of durvalumab to the standard backbone of chemotherapy for small cell lung cancer had its survival advantage. These patients are living longer and it was really an impressive improvement. And I think it really underscores just the revolution that has happened in lung cancer between targeted therapy and immunotherapy has completely changed the prognosis for patients with this disease. So to me, these were really landmark reports that came out at ASCO that really showed us how far we've come in oncology. Dr. John Sweetenham: Yeah, absolutely. I think that, as you mentioned, those results are truly remarkable, and they reflect extraordinary advances in science. I think we see that both in terms of the therapeutic arena, but also, I think we've started to see it in other areas as well, like symptom control, remote patient monitoring, and so on and so forth, where some of the newer virtual technologies are really having major impacts as well. Dr. Angela DeMichele: Yes, we really wanted to have a focus on artificial intelligence in this meeting, because it's having such an enormous impact on our field in everything from care delivery to diagnostics. I'd love to hear what you thought was the most interesting, because there really was just new data across the board presented. Dr. John Sweetenham: I've actually chosen 3 abstracts which I thought were particularly interesting for a couple of reasons, really. They're all based on virtual health interventions, and I think they're interesting in really reflecting the theme of the meeting, in that they are extremely advanced technology involved in the virtual platforms, a couple of which are artificial intelligence, but very impactful to patients at the same time in terms of remote symptom control, in terms of addressing disparities, and in one case, even influencing survival. So I thought these were three really interesting abstracts that I'll walk the listeners through very quickly.  The first of these was a study, Abstract 1500 (“National implementation of an AI-based virtual dietician for patients with cancer”) which looked at an artificial intelligence-based virtual dietitian for patients with cancer. This is based on the fact that we know nutritional status to be a key driver of patient experience and of cancer outcomes. And as the authors of the presentation noted, 80% of patients look for nutritional support, but many of them don't get it. And that's primarily a workforce issue. And I think that's an important thematic point as well, that these new technologies can help us to address some of the workforce issues we have in oncology. So this was an AI-based platform developed by experts in nutrition and cancer patients, based on peer reviewed literature, and a major effort in terms of getting all of these data up together. And they developed an artificial intelligence platform, which was predominantly text message based. And this platform was called INA. And as this is developing as a platform, there's a machine learning component to it as well. So in theory, it's going to get better and better and better over time.  And what they did in their study was they looked at little over 3,000 patients across the entire country who were suffering from various types of cancer, GU, breast, gynecological malignancy, GI and lung. And most of them had advanced-stage disease, and many of them had nutritional challenges. For example, almost 60% of them were either overweight or obese by BMI. And the patients were entered into a text exchange with the AI platform, which would give them advice on what they should eat, what they shouldn't eat. It would push various guidance and tips to them, it would develop personalized recipes for them, and it would even develop menu plans for the patients. And what's really interesting about this is that the level of engagement from the patients was very high, with almost 70% of patients actually texting questions to this platform. About 80% of the patients completed all of the surveys, and the average time that patients interacted with the platform was almost nine months, so this was remarkable levels of engagement, high levels of patient satisfaction. And although at this point, I think it's very early and somewhat subjective, there was certainly a very positive kind of vibe from patients. Nearly 50% have used the recommended recipes. More than 80% of them thought that their symptoms improved while they were using this platform. So I think as a kind of an assistant for remote management of patients, it's really remarkable. And the fact that the level of engagement was so high also means that for those patients, it's been very impactful.   The second one, this was Abstract 100 (“AI virtual patient navigation to promote re-engagement of U.S. inner city patients nonadherent with colonoscopy appointments: A quality improvement initiative”) looked again at an AI-based platform, which in this case was used in an underserved population to address healthcare disparities. This is a study from New York which was looking at colorectal cancer screening disparities amongst an underserved population, where historically they've used skilled patient navigators to address compliance with screening programs, in this case specifically for colorectal cancer. And they noticed in the background to this study that in their previous experience in 2022, almost 60% of patients either canceled or no-showed for colonoscopy appointments. And because of this and because of the high burden of patients that this group has, they decided to take an AI-based virtual patient navigator called MyEleanor and introduce this into their colorectal cancer screening quality improvement.  And so they introduced this platform in April of 2023 through to the end of the year, and their plan was to target reengagements of around 2,500 patients who had been non adherent with colonoscopy appointments in a previous year. And so the platform MyEleanor would call the patients to discuss rescheduling, it would assess their barriers to uptake, it would offer live transfer to somebody to schedule for them, and then it would go on closer to the point of the colonoscopy to call the patients and give them advice about their prep. And it was very nuanced. The platform would speak in both English and Spanish versions. It could detect nuances in the patient's voice, which might then trigger it to refer the patient to a live agent rather than the AI platform. So, very sophisticated technology. And what was most interesting about this, I think, was that over the eight months of the study, around 60% of patients actually engaged with this platform, with almost 60% of that group, or 33% overall, accepting a live transfer and then going on to scheduling, so that the completion rate for the no show patients went from 10% prior to the introduction of this platform to 19% after it was introduced. So [this is] another example, I think, of something which addresses a workforce problem and also addresses a major disparity within cancer care at the moment by harnessing these new technologies. And I think, again, a great interaction of very, very high-level science with things that make a real difference to our patients.  So, Dr. DeMichele, those are a couple of examples, I think, of early data which really are beginning to show us the potential and signal the impact that artificial intelligence is going to have for our patients in oncology. I wonder, do you have any thoughts right now of where you see the biggest impact of artificial intelligence; let's say not in 20 years from now, but maybe in the next year or two?  Dr. Angela DeMichele: Well, I think that those were two excellent examples. A really important feature of AI is really easing the workload on physicians. And what I hope will happen is that we'll be able to use AI in the very near future as a partner to really offload some of the quite time-consuming tasks, like charting, documentation, that really take us away from face-to-face interaction with patients. I think this has been a very difficult period where we move to electronic medical records, which are great for many reasons, but have really added to the burden to physicians in all of the extra documentation. So that's one way, I think, that we will hope to really be able to harness this. I think the other thing these abstracts indicate is that patients are very willing to interact with these AI chatbots in a way that I think, as you pointed out, the engagement was so high. I think that's because they trust us to make sure that what we're doing is still going to be overseen by physicians, that the information is going to get to us, and that they're going to be guided. And so I think that in areas where we can do outreach to patients, reminders, this is already happening with mammograms and other sorts of screening, where it's automated to make sure you're giving reminders to patients about things that they need to do for some of their basic health maintenance. But here, really providing important information – counseling that can be done by one of these chatbots in a way that is compassionate, informative and does not feel robotic to patients.   And then I was really impressed with, in the abstract on the screening colonoscopy, the ability of the AI instrument to really hear nuances in the patient's responses that could direct them directly to a care provider, to a clinician, if they thought that there might be some problem the patient was experiencing. So again, this could be something that could be useful in triaging phone calls that are coming in from patients or our portals that just feel like they are full of messages, no matter how hard you try to clear them all out, to get to them all. Could we begin to use AI to triage some of the more mundane questions that don't require a clinician to answer so that we can really focus on the things that are important, the things that are life threatening or severe, and make sure that we're getting to patients sooner? So there's just a few ways I really hope it'll help us. Dr. John Sweetenham: Yeah, absolutely. I think we're just scratching the surface. And interestingly enough, in my newsfeed this morning through email, I have an email that reads, “Should AI pick immunotherapy combinations?” So we'll see where that goes, and maybe one day it will. Who knows? Dr. Angela DeMichele There was a great study presented at ASCO about that very thing, and I think that is still early, but I could envision a situation where I could ask an AI instrument to tell me all of the data around something that I want to know about for a patient that could deliver all of the data to me in real time in the clinic to be able to help me make decisions, help me quote data to patients. I think in that way it could be very, very helpful. But it'll still need the physicians to be putting the data into context and thinking about how to apply it to the individual person. Dr. John Sweetenham: Absolutely, yes. And so just to round off, the final abstract that caught my eye, which I think kind of expands on a theme that we saw at an ASCO meeting two or three years ago around the impact of [oncology] care at home, and this was Abstract 1503 (“Acute care and overall survival results of a randomized trial of a virtual health intervention during routine cancer treatment”). So, a virtual platform but not AI in this case. And this was a study that looked at the use of an Integrative Medicine at Home virtual mind-body fitness program. And this was a platform that was used to look at hospital admission and acute care of patients who used it, and also looked at survival, interestingly enough. So what was done in this study was a small, randomized study which looked at the use of virtual live mind, body and fitness classes, and compared this in a randomized fashion to what they called enhanced usual care, which essentially consisted of giving the patients, making available to the patients, some pre-recorded online meditation resources that they could use. And this was applied to a number of patients with various malignancies, including melanoma, lung, gynecologic, head and neck cancers, all of whom were on systemic therapy and all of whom were reporting significant fatigue.  This was a small study; 128 patients were randomized in this study. And what was very interesting, to cut to the chase here, is that the patients who had the virtual mind-body program, compared with the control group, actually were less likely to be hospitalized, the difference there being 6.3% versus 19.1%, respectively. They spent fewer days in the hospital. And remarkably, the overall survival was 24.3 months median for patients in the usual care arm and wasn't reached in those patients who were on the virtual mind-body fitness class platform. So very preliminary data, certainly are going to need more confirmation, but another example of how it appears that many of these non-pharmacological interventions have the potential to improve meaningful endpoints, including hospital stays and, remarkably, even survival. So again, I think that that is very consistent with the theme of this year's meeting, and I found that particularly interesting, too.  I think our time is up, so I want to thank you, Dr. DeMichele, for sharing your insights with us today on the ASCO Daily News Podcast. We really appreciate it. And once again, I want to congratulate you on what was really a truly remarkable ASCO this year.  Dr. Angela DeMichele: Well, thanks so much for having me. It's been a tremendous pleasure to be with you today. Dr. John Sweetenham: And thank you to our listeners for joining us today. You'll find links to the abstracts discussed today in a transcript of this episode. 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 ASCO on social media:    @ASCO on Twitter    ASCO on Facebook    ASCO on LinkedIn      Disclosures:   Dr. John Sweetenham:   Consulting or Advisory Role: EMA Wellness  Dr. Angela DeMichele: Consulting or Advisory Role (an immediate family member): Pfizer Research Funding (Inst.): Pfizer, Genentech, Novartis, Inviata/NeoGenomics  

Nigerian Foreign Minister Yusuf Maitama Tuggar is in China on an official visit until Wednesday. He co-chaired the first Plenary Session of the China-Nigeria Inter-governmental Committee with Chinese Foreign Minister Wang Yi. We caught up with Minister Tuggar and chatted with him about China-Nigeria and China-Africa cooperation under the Belt and Road Initiative and the China-Africa Cooperation Forum.

Drs. Vamsi Velcheti and Nathan Pennell discuss novel approaches and key studies in lung cancer that were showcased at the 2024 ASCO Annual Meeting, including the Plenary abstracts LAURA and ADRIATIC.   TRANSCRIPT Dr. Vamsi Velcheti: Hello, I am Dr. Vamsi Velcheti, your guest host for the ASCO Daily News Podcast today. I'm a professor of medicine and director of thoracic medical oncology at the Perlmutter Cancer Center at NYU Langone Health. Today, I'm joined by Dr. Nate Pennell, the co-director of the Cleveland Clinic Lung Cancer Program and the vice chair of clinical research at the Taussig Cancer Center in Cleveland Clinic. Dr. Pennell is also the editor-in-chief of the ASCO Educational Book. Today, we will be discussing practice-changing abstracts and the exciting advances in lung cancer that were featured at the ASCO 2024 Annual Meeting. You'll find our full disclosures in the transcript of the episode. Nate, we're delighted to have you back on the podcast today. Thanks for being here. It was an exciting Annual Meeting with a lot of important updates in lung cancer. Dr. Nate Pennell: Thanks, Vamsi. I'm glad to be back. And yes, it was a huge year for lung. So I'm glad that we got a chance to discuss all of these late-breaking abstracts that we didn't get to talk about during the prelim podcast. Dr. Vamsi Velcheti: Let's dive in. Nate, it was wonderful to see all the exciting data, and one of the abstracts in the Plenary Session caught my attention, LBA3. In this study, the investigators did a comparative large-scale effectiveness trial of early palliative care delivered via telehealth versus in-person among patients with advanced non-small cell lung cancer. And the study is very promising. Could you tell us a little bit more about the study and your take-home messages? Dr. Nate Pennell: Yes, I think this was a very important study. So just to put things in perspective, it's now been more than a decade since Dr. Jennifer Temel and her group at Massachusetts General Hospital did a randomized study that showed that early interventions with palliative medicine consultation in patients with advanced non-small cell lung cancer significantly improves quality of life and in her initial study, perhaps even overall survival. And since then, there have been numerous studies that have basically reproduced this effect, showing that getting palliative medicine involved in people with advanced cancer, multiple different cancer types, really, has benefits.  The difficulty in applying this has been that palliative care-trained specialists are few and far between, and many people simply don't have easy access to palliative medicine-trained physicians and providers. So with that in mind, Dr. Temel and her group designed a randomized study called the REACH PC trial, where 1,250 patients were randomized with advanced non-small cell lung cancer to either in-person palliative medicine visits which is sort of the standard, or one in-person assessment followed by monthly telemedicine video visits with palliative medicine. Primary endpoint was essentially to show that it was equivalent in terms of quality of life and patient satisfaction. And what was exciting about this was that it absolutely was. I mean, pretty much across the board in all the metrics that were measured, the quality-of-life, the patient satisfaction, the anxiety and depression scores, all were equivalent between doing telemedicine visits and in-person visits. And this hopefully will now extend the ability to get this kind of benefit to a much larger group of people who don't have to geographically be located near a palliative medicine program. Dr. Vamsi Velcheti: Yeah, I think it's a great abstract, Nate and I actually was very impressed by the ASCO committee for selecting this for the Plenary. We typically don't see supportive care studies highlighted in such a way at ASCO. This really highlights the need for true interdisciplinary care for our patients. And as you said, this study will clearly address that unmet need in terms of providing access to palliative care for a lot of patients who otherwise wouldn't have access. I'm really glad to see those results. Dr. Nate Pennell: It was. And that really went along with Dr. Schuchter's theme this year of bringing care to patients incorporating supportive care. So I agree with you.  Now, moving to some of the other exciting abstracts in the Plenary Session. So we were talking about how this was a big year for lung cancer. There were actually 3 lung cancer studies in the Plenary Session at the Annual Meeting. And let's move on to the second one, LBA4, the LAURA study. This was the first phase 3 study to assess osimertinib, an EGFR tyrosine kinase inhibitor, in patients with EGFR mutant, unresectable stage III non-small cell lung cancer. What are your takeaways from this study?  Dr. Vamsi Velcheti: This is certainly an exciting study, and all of us in the lung community have been kind of eagerly awaiting the results of the study. As you know, for stage III non-small cell lung cancer patients who are unresectable, the standard of care has been really established by the PACIFIC study with the consolidation durvalumab after definitive concurrent chemoradiation. The problem with that study is it doesn't really answer the question of the role of immunotherapy in patients who are never-smokers, and especially in patients who are EGFR positive tumors, where the role of immunotherapy in a metastatic setting has always been questioned. And in fact, there have been several studies as you know, in patients with EGFR mutation positive metastatic lung cancer where immunotherapy has not been that effective. In fact, in the subgroup analysis in the PACIFIC study, patients with EGFR mutation did not really benefit from adding immunotherapy.  So this is an interesting study where they looked at patients with locally advanced, unresectable stage III patients and they randomized the patients 2:1 to osimertinib versus placebo following concurrent or sequential tumor radiation. The primary endpoint for the study was progression free survival, and a total of 216 patients were enrolled and 143 patients received a study treatment, which is osimertinib, and 73 received placebo. And 80% of the patients on the placebo arm crossed over to getting treatment at the time of progression.  So most of us in the lung cancer community were kind of suspecting this would be a positive trial for PFS. But however, I think the magnitude of the difference was truly remarkable. The median PFS in the osimertinib arm was 39.1 months and placebo was 5.6 months and the hazard ratio of 0.16. So it was a pretty striking difference in terms of DFS benefit with the osimertinib consolidation following chemoradiation. So it was truly a positive study for the primary endpoint and the benefit was seen across all the subgroups and the safety was no unexpected safety signals other than a slight increase in the radiation pneumonitis rates in patients receiving osimertinib and other GI and skin tox were kind of as expected. In my opinion, it's truly practice changing and I think patients with EGFR mutation should not be getting immunotherapy consolidation post chemoradiation. Dr. Nate Pennell: I completely agree with you. I think that this really just continues the understanding of the use of osimertinib in EGFR-mutant lung cancer in earlier stages of disease. We know from the ADAURA trial, presented twice in the Plenary at the ASCO Annual Meeting, that for IB, stage II and resectable IIIA, that you prolong progression free or disease free survival. So this is a very similar, comparable situation, but at an even higher risk population or the unresectable stage III patients. I think that the most discussion about this was the fact that the osimertinib is indefinite and that it is distinct from the adjuvant setting where it's being given for three years and then stopped. But I think all of us had some pause when we saw that after three years, especially in the stage III patients from ADAURA, that there were clearly an increase in recurrences after stopping the drug, suggesting that there are patients who are not cured with a time limited treatment, or at least with 3 years of treatment.  The other thing that is sobering from the study, and was pointed out by the discussant, Dr. Lecia Sequist, is if you look at the two-year disease-free survival in the placebo arm, it was only 13%, meaning almost no one was really cured with chemo radiation alone. And that really suggests that this is not that different from a very early stage IV population where indefinite treatment really is the standard of care. I wonder whether you think that's a reasonable approach. Dr. Vamsi Velcheti: I completely agree with you, Nate, and I don't think we cure a majority of our patients with stage III, and less so in patients who have EGFR-mutant, stage III locally advanced. As you just pointed out, I think very few patients actually make it that far along. And I think there's a very high rate of CNS micrometastatic disease or just systemic micrometastatic disease in this population that an effective systemic therapy of osimertinib can potentially have long term outcomes. But again, we perhaps don't cure a vast majority of them. I think that the next wave of studies should incorporate ctDNA and MRD-based assays to potentially identify those patients who could potentially go off osimertinib at some point. But, again, outside of a trial, I would not be doing that. But I think it's definitely an important question to ask to identify de-escalation strategies with osimertinib. And even immunotherapy for that matter, I think we all know that not all patients really require years and years of immunotherapy. They're still trying to figure out how to use immunotherapy in these post-surgical settings, using the MRD to de-escalate adjuvant therapies. So I think we have to have some sort of strategy here. But outside of a clinical trial, I will not be using those assays here to cite treatments, but certainly an important question to ask.  Moving on to the other exciting late-breaking abstracts, LBA5, the ADRIATIC study. This is another study which was also in the plenary session. This study was designed to address this question of consolidation immunotherapy, post chemo radiation for limited-stage small cell cancer, the treatment arms being durvalumab tremelimumab, and durvalumab observation. So what do you think about the study? This study also received a lot of applause and a lot of attention at the ASCO meeting. Dr. Nate Pennell: It was. It was remarkable to be there and actually watch this study as well as the LAURA study live, because when the disease free survival curves and in the ADRIATIC study, the overall survival curves were shown, the speakers were both interrupted by standing ovation of applause just because there was a recognition that the treatment was changing kind of before our eyes. I thought that was really neat. So in this case, I think this is truly a historic study, not necessarily because it's going to necessarily be an earth shakingly positive study. I mean, it was clearly a positive study, but more simply because of the disease in which it was done, and that is limited-stage small cell lung cancer. We really have not had a change in the way we've treated limited-stage small cell lung cancer, probably 25 years. Maybe the last significant advances in that were the advent of concurrent chemotherapy and radiation and then the use of PCI with a very modest improvement in survival. Both of those, I would say, are still relatively modest advances.  In this case, the addition of immunotherapy, which we know helps patients with small cell lung cancer - it's of course the standard of care in combination chemotherapy for extensive stage small cell lung cancer - in this case, patients who completed concurrent chemo radiation were then randomized to either placebo or durvalumab, as well as the third arm of durvalumab tremelimumab, which is not yet been recorded, and co primary endpoints were overall survival and progression free survival. And extraordinarily, there was an improvement in overall survival seen at the first analysis, with a median overall survival of 55.9 months compared to 33.4 months, hazard ratio of 0.73. So highly clinically and statistically significant, that translates at three years to a difference in overall survival of 56.5%, compared to 47.6%, or almost 10% improvement in survival at three years.  There was also a nearly identical improvement in progression-free survival, also with a hazard ratio of 0.76, suggesting that there's a modest number of patients who benefit. But it seems to be a clear improvement with the curves plateauing out. In my opinion, this is very comparable to what we saw with the PACIFIC study in stage III, unresectable non-small cell lung cancer, which immediately changed practice back when that first was reported. And I expect that this will change practice pretty much immediately for small cell as well. Dr. Vamsi Velcheti: Yeah, I completely agree, Nate. I think it's an exciting advance in patients with limited-stage small cell lung cancer. For sure, it's practice-changing, and I think the results were exciting.  So one thing that really intrigued me was in the extensive-stage setting, the benefit was very mediocre with one-to-two month overall survival benefit in both the PACIFIC and in IMpower trial. Here we are seeing almost two-year of median OS benefit. I was kind of puzzled by that, and I thought it may have to do with patients receiving radiation. And we've seen that with the PACIFIC, and makes you wonder if both the CASPIAN and the IMpower studies actually did not allow consolidation thoracic radiation. Hypothetically, if they had allowed consolidation thoracic radiation, perhaps we would have seen better outcomes. Any thoughts on that? Dr. Nate Pennell: We've been trying to prove that radiation and immunotherapy somehow go together better for a long time. Going back to the first description of the abscopal effect, and I'm not sure if I necessarily believe that to be the case, but in this setting where we truly are trying to cure people rather than merely prolong their survival, maybe this is the situation where it truly is more beneficial. I think what we're seeing is something very similar to what we're seen in PACIFIC, where in the stage IV setting, some people have long term survival with immunotherapy, but it's relatively modest. But perhaps in the curative setting, you're seeing more of an impact. Certainly, looking at these curves, we'll have to see with another couple of years to follow up. But a three-year survival of 56% is pretty extraordinary, and I look forward to seeing if this really maintains over the next couple of years follow up.  Moving beyond the Plenary, there were actually lots of really exciting presentations, even outside the Plenary section. One that I think probably got at least as much attention as the ones that we've already discussed today was actually an update of an old trial that's been presented for several prior years. And I'm curious to get your take on why you thought this was such a remarkable study. And we're talking about the LBA8503, which was the 5-year update from the CROWN study, which looked at previously untreated ALK-positive advanced non-small cell in cancer patients randomly assigned to lorlatinib, the third generation ALK inhibitor, versus crizotinib, the first generation ALK inhibitor. What was so exciting about this study, and why were people talking about it?  Dr. Vamsi Velcheti: Yeah, I agree, Nate. We've seen the data in the past, right? Like on the CROWN data, just first like a quick recap. This is the CROWN study, like the phase 3 study of third generation ALK inhibitor lorlatinib. So global randomized phase 3 study in patients with metastatic disease randomized to lorlatinib versus crizotinib, which is a controller. So the primary endpoint was PFS, and we've seen the results in the past of the CROWN readout quoted, with a positive study and the lorlatinib received FDA approval in the frontline setting. But the current study that was presented at the ASCO annual meeting is a kind of a postdoc analysis of five years. The endpoint for the study with central review stopped at three years, and this is actually a follow up beyond that last readout. Interestingly, in this study, when they looked at the median PFS at five years, the lorlatinib arm did not reach a median PFS even at five years and the hazard ratio is 0.19, which is kind of phenomenal in some ways. At 5 years, the majority of the patients were still on the drug. So that's quite incredible. And the benefit was more profound in patients with brain mets with a hazard ratio of 0.08. And again, speaking to the importance of brain penetrant, small molecule inhibitors, and target therapy, the safety profile, there were no additional safety signals noted in the study. We kind of know about the side effects of lorlatinib already from previous studies readouts. No unusual long-term toxicities.  I should note though, about 40% of patients did have CNS, AEs grade 1, 2 CNS toxicities on the  lorlatinib arm. And the other interesting thing that was also reported in the trial was dose reduction of lorlatinib did not have an impact on the PFS, which is interesting in my opinion. They also did some subgroup analysis, biomarker testing, biomarker populations. Patients who had P53 cooperation did much better with lorlatinib versus crizotinib. So overall, the other thing that they also had shown on the trial was the resistance mechanisms that were seen with lorlatinib were very different than what we are used to seeing with the earlier generation ALK inhibitors. The majority of the patients who develop resistance have bypass mechanisms and alterations in MAP kinase pathway PI3K/MTOR/PTEN pathway, suggesting that lorlatinib is a very potent ALK inhibitor and on target ALK mutations don't happen as frequently as we see with the earlier generation ALK inhibitors.  So I think this really begs the question, should we offer lorlatinib to all our patients with metastatic ALK-positive tumors? I think looking at the long-term data, it's quite tempting to say ‘yes', but I think at the same time we have to take into consideration patient safety tolerability. And again, the competitor arm here is crizotinib. So lorlatinib suddenly seems to be, again, cross trial comparisons, but I think the long-term outcomes here are really phenomenal. But at the same time, I think we've got to kind of think about patient because these patients are on these drugs for years, they have to live with all the toxicities. And I think the patient preferences and safety profile matters in terms of what drug we recommend to patients. Dr. Nate Pennell: I completely agree with you. I think the right answer, is that this has to be an individual discussion with patients. The results are incredibly exciting. I mean, the two-year progression free survival was 70%, and the five-year, three years later is still 60%. Only 10% of people are failing over the subsequent three years. And the line is pretty flat. And as you said, even with brain metastases, the median survival is in reach. It's really extraordinary. Moreover, while we do talk about the significant toxicities of lorlatinib, I thought it was really interesting that only 5% of people were supposedly discontinued the drug because of treatment related AEs, which meant that with dose reduction and management, it seems as though most patients were able to continue on the drug, even though they, as you mentioned, were taking it for several years.  That being said, all of us who've had experience with the second-generation drugs like alectinib and brigatinib, compared to the third-generation drug lorlatinib, can speak to the challenges of some of the unique toxicities that go along with it. I don't think this is going to be a drug for everyone, but I do think it is now worth bringing it up and discussing it with the patients most of the time now. And I do think that there will be many people for whom this is going to be a good choice, which is exciting. Dr. Vamsi Velcheti: Absolutely, completely agree. And I think there are newer ALK inhibitors in clinical development which have cleaner and better safety profiles. So we'll have to kind of wait and see how those pan out.  Moving on to the other exciting abstract, LBA8509, the KRYSTAL-12 study. LBA8509 is a phase 3 study looking at adagrasib versus docetaxel in patients with previously treated advanced metastatic non-small cell cancer with KRASG12C mutation. Nate, there's been a lot of hype around this trial. You've seen the data. Do you think it's practice-changing? How does it differentiate with the other drug that's already FDA approved, sotorasib?  Dr. Nate Pennell: Yeah, this is an interesting one. I think we've all been very excited in recent years about the identification of KRASG12C mutations as targetable mutations. We know that this represents about half of KRAS mutations in patients with non-small cell lung cancer, adenocarcinoma, and there are two FDA-approved drugs. Sotorasib was the first and adagrasib shortly thereafter. We already had seen the CodeBreaK 200 study, which was a phase 3 study of sotorasib versus docetaxel that did modestly prolong progression free survival compared to docetaxel, although did not seem to necessarily translate to an improvement in overall survival. And so now, coming on the heels of that study, the KRYSTAL-12 study compared adagrasib, also the KRASG12C  inhibitor versus docetaxel and those with previously treated non-small cell with KRASG12C. And it did significantly improve progression free survival with a hazard ratio of 0.58. Although when you look at the median numbers, the median PFS was only 5.5 months with the adagrasib arm compared to 3.8 months with docetaxel. So while it is a significant and potentially clinically significant difference, it is still, I would say a modest improvement.   And there were some pretty broad improvements across all the different subgroups, including those with brain metastases. It did improve response rate significantly. So 32% response rate without adagrasib, compared to only 9% with docetaxel. It's about what you would expect with chemotherapy. And very importantly, in this patient population, there was activity in the brain with an intracranial overall response rate among those who had measurable brain metastases of 40%. So certainly important and probably that would distinguish it from drugs like docetaxel, which we don't expect to have a lot of intracranial toxicity. There is certainly a pattern of side effects that go along with that adagrasib, so it does cause especially GI toxicity, like diarrhea, nausea, vomiting, transaminitis. All of these were actually, at least numerically, somewhat higher in the adagrasib arm than in docetaxel, a lot more hematologic toxicity with the docetaxel. But overall, the number of serious adverse events were actually pretty well matched between the two groups. So it wasn't really a home run in terms of favorable toxicity with that adagrasib.  So the question is: “In the absence of any data yet on overall survival, should this change practice?” And I'm not sure it's going to change practice, because I do think that based on the accelerated approval, most physicians are already offering the G12C inhibitors like sotorasib and adagrasib, probably more often than chemotherapy, I think based on perceived improvement in side effects and higher response rates, modestly longer progression-free survival, so I think most people think that represents a modest improvement over chemotherapy. And so I think that will continue. It will be very interesting, however, when the overall survival report is out, if it is not significantly better, what the FDA is going to do when they look at these drugs.  Dr. Vamsi Velcheti: Thanks so much. Very well summarized. And I do agree they look more similar than dissimilar. I think CodeBreaK-200 and the KRYSTAL-12, they kind of are very identical. I should say, though I was a little surprised with the toxicity profile of adagrasib. It seemed, I mean, not significantly, but definitely seemed worse than the earlier readouts that we've seen. The GI tox especially seems much worse on this trial. I'm kind of curious why, but if I recall correctly, I think 5% of the patients had grade 3 diarrhea. A significant proportion of patients had grade 3 nausea and vomiting. And the other complicating thing here is you can't use a lot of the antiemetics because of the QT issues. So that's another problem. But I think it's more comparable to sotorasib, in my opinion.  Dr. Nate Pennell: While this is exciting, I like to think of this as the early days of EGFR, when we were using gefitinib and erlotinib. They were certainly advances, but we now have drugs that are much more effective and long lasting in these patients. And I think that the first-generation inhibitors like sotorasib and adagrasib, while they certainly benefit patients, now is just the beginning. There's a lot of research going on, and we're not going to talk about some of the other abstracts presented, but some of the next generation G12C inhibitors, for example, olomorasib, which did have also in the same session, a presentation in combination with pembrolizumab that had a very impressive response rate with potentially fewer side effects, may end up replacing the first generation drugs when they get a little bit farther along. And then moving on to another one, which I think potentially could change practice. I am curious to hear your take on it, was the LBA8505, which was the PALOMA-3 study. This was interesting in that it compared two different versions of the same drug. So amivantamab, the bispecific, EGFR and MET, which is already approved for EGFR exon 20 non-small cell lung cancer, in this case, in more typical EGFR-mutated non-small cell lung cancer in combination with osimertinib with the intravenous amivantamab, compared to the subcutaneous formulation of amivantamab. Why would this be an important study? Dr. Vamsi Velcheti: I found this study really interesting as well, Nate. And as you know, amivantamab has been FDA approved for patients with exon 20 mutation. And also, we've had, like two positive readouts in patients with classical EGFR mutations. One, the MARIPOSA study in the frontline setting and the MARIPOSA-2, in the second-line post osimertinib setting. For those studies, the intravenous amivantamab was used as a treatment arm, and the intravenous amivantamab had a lot of baggage to go along with it, like the infusion reactions and VTEs and other classic EGFR related toxicity, skin toxicities. So the idea behind developing the subcutaneous formulation of amivantamab was mainly to reduce the burden of infusion, infusion time and most importantly, the infusion related reactions associated with IV formulation.  In a smaller phase 2 study, the PALOMA study, they had looked at various dosing schemas like, subcutaneous formulation, and they found that the infusion related reactions were very, very low with the subcutaneous formulation. So that led to the design of this current study that was presented, the PALOMA-3 study. This was for patients who had classical EGFR mutations like exon 19, L858R. The patients were randomized 1:1 to subcutaneous amivantamab with lazertinib versus IV amivantamab plus lazertinib. The endpoints for the study, it's a non-inferiority study with co primary endpoints of C trough and C2 AUC, Cycle 2 AUC. They were looking at those pharmacological endpoints to kind of demonstrate comparability to the IV formulation. So in this study, they looked at these pharmacokinetic endpoints and they were essentially identical. Both subcutaneous and IV formulations were compatible. And in terms of clinical efficacy as well, the response rate was identical, no significant differences. Duration of response was also identical. The PFS also was comparable to the IV formulation. In fact, numerically, the subcutaneous arm was a little better, though not significant. But it appears like, you know, the overall clinical and pharmacological profile of the subcutaneous amivantamab was comparable. And most interestingly, the AE profile, the skin toxicity was not much different. However, the infusion reactions were substantially lower, 13% with the subcutaneous amivantamab and 66% with IV amivantamab. And also, interestingly, the VTE rates were lower with the subcutaneous version of amivantamab. There was still a substantial proportion of patients, especially those who didn't have prophylactic anticoagulation. 17% of the patients with the subcutaneous amivantamab had VTE versus 26% with IV amivantamab. With prophylaxis, which is lower in both IV and subcutaneous, but still subcutaneous formulation at a lower 7% versus 12% with the IV amivantamab.  So overall, I think this is an interesting study, and also the authors had actually presented some interesting data on administration time. I've never seen this before. Patients reported convenience using a modified score of patient convenience, essentially like patients having to spend a lot of time in the infusion site and convenience of the patient getting the treatment. And it turns out, and no surprise, that subcutaneous amivantamab was found to be more convenient for patients.  So, Nate, I want to ask you your take on this. In a lot of our busy infusion centers, the time it takes for those patients to get the infusion does matter, right? And I think in our clinic where we are kind of fully booked for the infusion, I think having the patients come in and leave in 15, 20 minutes, I think it adds a lot of value to the cancer center operation.  Dr. Nate Pennell: Oh, I completely agree. I think the efficacy results were reassuring. I think the infusion related reaction difference, I think is a huge difference. I mean, I have given a fair amount of amivantamab, and I would say the published IRR rate of 66%, 67% I would say, is maybe even underestimates how many patients get some kind of reaction from that, although it really is a first dose phenomenon. And I think that taking that down to 13% is a tremendous advance. I think fusion share time is not trivial as we get busier and busier. I know our cancer center is also very full and it becomes challenging to schedule people, and being able to do a five-minute treatment versus a five-hour treatment makes a big difference for patients.  It's interesting, there was one slide that was presented from an efficacy standpoint. I'm curious about your take on this. They showed that the overall survival was actually better in the subcu amivantamab arm, hazard ratio of 0.62. Now, this was only an exploratory endpoint. They sort of talk about perhaps some rationale for why this might be the case. But at the very least, I think we can be reassured that it's not less effective to give it and does seem to be more tolerable and so I would expect that this hopefully will be fairly widely adopted. Dr. Vamsi Velcheti: Yeah, I agree. I think this is a welcome change. Like, I think the infusion reactions and the resources it takes to get patients through treatments. I think it's definitely a win-win for patients and also the providers.  And with that, we come to the conclusion of the podcast. Nate, thank you so much for the fantastic insights today. Our listeners will find all the abstracts discussed today in the transcripts of the episode. Thank you so much for joining us today, Dr. Pennell.  Dr. Nate Pennell: Oh, thanks for inviting me. It's always fun to talk about all these exciting advances for our patients. Dr. Vamsi Velcheti: Thanks to our listeners for your time today. You will find links to all the abstracts discussed today in the transcript of the episode. Finally, if you value the insights that you hear from ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcast.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Find out more about today's speakers:    Dr. Vamsi Velcheti  @VamsiVelcheti    Dr. Nathan Pennell  @n8pennell    Follow ASCO on social media:      @ASCO on Twitter    ASCO on Facebook    ASCO on LinkedIn      Disclosures:  Dr. Vamsi Velcheti:  Honoraria: ITeos Therapeutics  Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen, Elevation Oncology, Taiho Oncology, Merus  Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline  Dr. Nathan Pennell:    Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron   Research Funding (Inst): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi

Dr. Shaalan Beg highlights practice-changing studies in GI cancers featured at the 2024 ASCO Annual Meeting, including the ESOPEC trial in esophageal adenocarcinoma and durable responses to PD-1 blockade alone in mismatch repair-deficient locally advanced rectal cancer. TRANSCRIPT Geraldine Carroll: Welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. My guest today is Dr. Shaalan Beg, an adjunct associate professor at UT Southwestern Simmons Comprehensive Cancer Center. Dr. Beg will be discussing practice- changing abstracts and other key advances in GI oncology that were presented at the 2024 ASCO Annual Meeting. His full disclosures are available in the transcript of this episode.  Dr. Beg, thanks for being on the podcast today.  Dr. Shaalan Beg: Thank you for having me. Geraldine Carroll: Let's begin with LBA1, the ESOPEC trial. This was featured in the Plenary Session, and this study compared two treatment strategies for locally advanced esophageal adenocarcinoma that could be treated with surgery. The strategies include the CROSS protocol, which consisted of chemoradiotherapy before surgery, and the FLOT protocol of chemotherapy before and after surgery. Can you tell us about this practice-changing study, Dr. Beg? Dr. Shaalan Beg: Yes. According to this study, perioperative chemotherapy with FLOT was better than neoadjuvant therapy with chemoradiation and carbo-taxol for people with adenocarcinoma of the esophagus. There were 438 patients enrolled on this phase 3 study. R0 resection rates were fairly similar across both groups. The PCR rates were a little higher on the FLOT group. But when you look at the median overall survival difference, 66 months in the FLOT group versus 37 months in the CROSS group, 3-year survival was 57% versus 50% favoring FLOT therapy as well.  So a couple of caveats on this clinical trial, because the first thing to note is that the standard treatment for this disease has evolved because we now don't only give CROSS chemoradiation, we also give immunotherapy after the completion of chemoradiation for this group of patients. And in this study, since it predated that standard of care, patients did not receive immunotherapy. But having said that, the take home for me here is that chemotherapy is better than chemoradiation for this group of patients, recognizing the fact that 1) they only enrolled adenocarcinoma patients, and 2) patients with high T stage were not included. So the folks with high T stage would be those who we would expect would benefit from the radiation aspect. So my take home here is that more chemotherapy is better in the perioperative space. Radiation should be considered for individuals who need more local control. But in general, I think we're going to see us moving more towards chemotherapy-based regimens with FLOT for this group of patients. Geraldine Carroll: Great. So moving on to rectal cancer, in LBA3512, investigators reported durable, complete responses to PD-1 blockade alone in mismatch repair deficient locally advanced rectal cancer. Can you tell us more about the promising durable responses that occurred in this trial?  Dr. Shaalan Beg: On first glance, seeing that immunotherapy has good activity in patients with mismatched repair deficient rectal cancer isn't really headline breaking news anymore. We've known about this activity for this group of patients for many years. Earlier at ASCO, the investigators presented early results of this compound for people receiving six months of dostarlimab therapy for people with mismatched repair deficient, locally advanced rectal cancer, and showed that they had a very high complete response rate. At that time, it generated a lot of interest and there was a lot of curiosity on whether these outcomes will be sustained. We don't know other characteristics of their biologic status and whether this was some sort of reflection of the patients who are selected or not.   So here in this presentation at ASCO 2024, they did come back to present follow-up data for people with mismatch repair deficient colorectal cancer, having received 6 months of dostarlimab. Forty-seven patients had been enrolled, and the 41 patients who had achieved a clinical complete response continued to have disease control with no distant metastases. So that's very compelling information. There were no additional serious adverse events greater than grade 2 that they saw, and they did follow circulating tumor DNA, and those did normalize even before they had their colonoscopy to examine their tumors.  So, again, we're continuing to see very encouraging data of immunotherapy, and the response rate with dostarlimab seems to be very interesting for this disease, and it will be interesting to see how this pans out in larger studies and how this translates into the use of dostarlimab across other diseases where other checkpoint inhibitors are currently being used. Geraldine Carroll: Absolutely. So, moving on to LBA3501. The COLLISION trial looked at surgery versus thermal ablation for small cell colorectal liver metastases. This was an international, multicenter, phase 3, randomized, controlled trial. How will this study change clinical practice?  Dr. Shaalan Beg: Kudos to the investigators here. They looked to understand the difference in outcome in treating people with colorectal cancer with liver only metastases. These clinical trials are extremely difficult to design. They're very difficult to enroll on because of the multidisciplinary aspect of the interventions and patient and provider biases as well. So on this clinical trial, the investigators enrolled people with resectable colorectal cancer, liver metastases so they did not have any metastases outside the liver. Patients were required to have 10 or less known metastases that were less than 3 cm in size. There were other allowances for larger tumors as well. And after an expert panel review, patients were randomized to either resection or ablation. It was up to the physicians whether they performed these laparoscopically or openly or percutaneously, depending on the biology of the patient and the anatomical presentation.  There was a predefined stopping rule at the half-time for this clinical trial, which showed a benefit in the experimental arm of ablation compared to standard of care. The overall survival was not compromised. Progression-free survival was not compromised with local therapy. But there were differences in morbidity and mortality, as we would expect, one being a surgical procedure and the other being ablation, where, according to this study, of the 140 or so patients who received either treatment, 2.1% of people who underwent resection died within 90 days of surgery. The AE rate was 56% in the resection sample compared to 19% in ablation, and the 90-day mortality for ablation was 0.7%. So less morbidity, improved mortality, reduced adverse events with ablation versus surgical resection without compromising local control and overall survival.   And I think for practice here in the United States, this does provide very interesting data for us to take back to the clinic for lesions that are relatively small and could generally be addressed by both surgery and ablation. Historically, there are various non biologic factors that could go into deciding whether someone should have surgery or ablation, and it could be based on who the physician is, who's seeing the patient, what the practice patterns in a specific organization are, and where their expertise lie. But here we're seeing that ablation for the small lesions is a very effective tool with very good local control rates, and again, in this selected group of patients with liver only metastases. And I think it is going to make tumor board discussions very interesting with data backing ablation for these lesions. Geraldine Carroll: Well, let's move onto the MOUNTAINER study. This study created some buzz in the colorectal cancer space. That's Abstract 3509. Can you tell us about the final results of this phase 2 study of tucatinib and trastuzumab in HER2-positive metastatic CRC? What are your thoughts on this treatment option, which seems to be well tolerated? Dr. Shaalan Beg: So, HER2 overexpression or amplification occurs in about 3 to 5% of patients with metastatic colorectal cancer and up to 10% of people who have a RAS/RAF wild type disease. On the previous episodes of the podcast we have covered precision targeted therapy in colorectal cancer, focusing on c-MET, focusing on BRAF, and here we have updated results targeting HER2 for colorectal cancer. And the results of the MOUNTAINEER study have been out for a while. This is a phase 2 study looking at combining tucatinib which is a highly selective HER2 directed TKI with trastuzumab, the monoclonal antibody for HER2 targeting. And what they found on this study is the confirmed overall response rate was 38%. Duration of response was 12 months, overall survival was 24 months and these are the results that have been already released and now we have an additional 16 months of follow up and these results continue to hold on. PFS and overall survival gains were held, which makes it a very interesting option for people with colorectal cancer. You mentioned the tolerability aspect and side effects. I think it's important to know the spectrum of side effects for this disease may be a little different than other TKIs. There's hypertension, but there's also the risk of diarrhea, back pain and pyrexia, with the most common grade 3 treatment related adverse event was an increase in AST level seen in 10% of people of grade 3 and above.  So where does that really leave us? There is a confirmatory randomized first-line trial of tucatinib and trastuzumab in the first line setting, which is currently ongoing. So we'll stay tuned to see where that leads us. And with the HER2 space right now for colorectal cancer with the development of antibody drug conjugates, we may have more than one option for this group of patients once those trials read out. Geraldine Carroll: Excellent. Well, moving on to LBA4008, that's the CheckMate-9DW trial. This trial reported first results looking at nivolumab plus ipilimumab versus sorafenib or lenvatinib as first-line treatment for advanced hepatocellular carcinoma. Can you tell us about this trial? Will there be a potential new standard of care in advanced HCC? Dr. Shaalan Beg: When we think about patients with advanced HCC, the only treatment option that they had for about a decade and a half were just oral track tyrosine kinase inhibitors that had modest to moderate clinical activity. Since then, we've seen that combination therapy is better than TKI therapy, and the combination therapy has taken two different forms. One is a combination of checkpoint inhibitor and antiangiogenic therapy, such as in the combination of atezolizumab and bevacizumab. The other is a combination of dual checkpoint inhibitor therapy. Here we are talking about the results of nivolumab and ipilimumab. Previously, we've talked about the combination of durva and tremi for the treatment of patients with HCC.   So in this study, nivo was given for the first 4 cycles, nivo and ipi were given together, nivo 1 mg per kg, and IPI 3 mgs per kg every 3 weeks for 4 cycles. And then the CTLA-4 inhibitor ipilimumab was stopped. And this was followed by monotherapy nivolumab every 4 weeks until disease progression or up to 2 years. And it was compared to dealers' choice, lenvatinib or sorafenib. The median overall survival of nivo-ipi was 23 months versus 20 months with lenvatinib-sorafenib. The 24-month overall survival was 49% with ipi-nivo versus 39%. And the overall response rate with nivo-ipi was 36% compared to 13%. So again, significantly improved clinical activity.   And when we talk about immunotherapy combinations, the question that comes to mind is how well is this tolerated? There's a lot of work and iteration that took place in figuring out what the right combination strategy of ipi and nivo should be, because some of the earlier studies did demonstrate fairly high adverse events in this group of patients. So on this study, we saw that grade 3 or 4 treatment related adverse events were seen in 41% of people who received nivo-ipi and 42% if they received lenvatinib or sorafenib. So, certainly a high proportion of treatment related adverse events, but probably also reflective of the disease population, which is being tested, because those numbers were fairly similar in the control arm as well.  So we've known that nivo-ipi is active in HCC. There is an approval in the second-line space, so it remains to be seen if this data helps propel nivo-ipi to the first-line space so we end up with another combination regimen for patients with advanced hepatocellular carcinoma.  Geraldine Carroll: Excellent. Well, before we wrap up the podcast, I'd like to ask you about LBA3511. In this study, investigators looked at total neoadjuvant treatment with long course radiotherapy versus concurrent chemoradiotherapy in local advanced rectal cancer with high risk factors. So this was a multicenter, randomized, open label, phase 3 trial. What are your key takeaways here? Dr. Shaalan Beg: Key takeaway here is that total neoadjuvant therapy was better than the conventional chemoradiation followed by chemo. So this clinical trial enrolled people with T4a/b resectable disease with clinical N2 stage, and they were randomized, as you mentioned, to receiving chemoradiation with radiation capecitabine followed by surgery, and then CAPOX or capecitabine versus chemo, short-course radiation, and additional chemotherapy followed by surgery.  And when we compare both arms, the total neoadjuvant therapy led to improved disease-free survival, improved PCR rates compared to standard concurrent neoadjuvant chemo radiotherapy in this group of patients. The two arms were fairly well-balanced. The number of T4 lesions was a little higher in the chemoradiation group. There were 49% in the chemo radiation group versus 46% had clinically T4 disease, but the nodal status was fairly similar. We should keep in mind that the other baseline characteristics were fairly well balanced.  And when we look at the outcomes, the disease-free survival probability at 36 months was 76% in the total neoadjuvant group compared to 67% with chemoradiation. And the metastasis free survival in total neoadjuvant therapy was 81% versus 73%. So a fairly compelling difference between the two arms, which did translate into an overall survival of 89% versus 88% in the two groups. So definitely higher disease-free survival and metastasis free survival, no difference on the overall survival with these groups. And it talks about the importance of intensifying chemotherapy upfront in this group of patients who can have a fairly high burden of disease and may struggle with receiving chemotherapy postoperatively. Geraldine Carroll: Excellent. Well, thank you, Dr. Beg, for sharing your fantastic insights with us on these key studies from the 2024 ASCO Annual Meeting. It's certainly a very exciting time in GI oncology. Dr. Shaalan Beg: Absolutely. Thank you for bringing these studies out, because I think a lot of these are practice-changing and can start impacting the clinical care that we're giving our patients right now. Geraldine Carroll: Thank you to our listeners for joining us today. You'll find links to the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the 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. Statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Find out more about today's speakers: Dr. Shaalan Beg   @ShaalanBeg     Follow ASCO on social media:   @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn    Disclosures:  Dr. Shaalan Beg:   Consulting or Advisory Role: Ispen, Cancer Commons, Foundation Medicine, Genmab/Seagen   Speakers' Bureau: Sirtex   Research Funding (An Immediate Family Member): ImmuneSensor Therapeutics   Research Funding (Institution): Bristol-Myers Squibb, Tolero Pharmaceuticals, Delfi Diagnostics, Merck, Merck Serono, AstraZeneca/MedImmune  

Dr. Diwakar Davar and Dr. Jason Luke discuss advances in the neoadjuvant immunotherapy space that were presented at the 2024 ASCO Annual Meeting, including promising outcomes in high-risk melanoma from the NADINA trial, as well as other new treatment options for patients with advanced cancers.    TRANSCRIPT Dr. Diwakar Davar: Hello and welcome to the ASCO Daily News Podcast. I'm your guest host, Dr. Diwakar Davar, and I am an associate professor of medicine and the clinical director of the Melanoma Skin Cancer Program at the University of Pittsburgh's Hillman Cancer Center. I am delighted to have my colleague and friend Dr. Jason Luke on the podcast today to discuss key late-breaking abstracts and advances in immunotherapy that were presented at the 2024 ASCO Annual Meeting. Dr. Luke is an associate professor of medicine, the associate director of clinical research, and the director of the Cancer Immunotherapeutic Center at the University of Pittsburgh Hillman Cancer Center.   You will find our full disclosures in the transcript of this episode.  Jason, it's always a pleasure to hear your insights on the key trials in these spaces and to have you back as a guest on this podcast that highlights some of the work, especially advances, that were just presented. Dr. Jason Luke: Well, thanks very much for the invitation. I always love joining the podcast. Dr. Diwakar Davar: We'll start very quickly by talking about some advances and really interesting things that happened both in the context of melanoma but also in immunotherapy in general. And we'll start with what I think was certainly one highlight for me, which was LBA2, the late-breaking abstract on the NADINA trial. It was featured in the Plenary Session, and in this abstract, Dr. Christian Blank and colleagues reported on the results of this phase 3 trial of neoadjuvant ipi-nivo. This is the flipped dose of ipi1/nivo3 versus adjuvant nivolumab in PD-1 naive, macroscopic, resectable, high-risk stage 3 melanoma.  By way of background, neoadjuvant immunotherapy for those listening is an area of increasing interest for drug developers and development for both approved and novel agents. Neoadjuvant immunotherapy has been studied with multiple approved agents, including PD-1 monotherapy, PD-1 LAG-3, PD-1 CTLA-4, T-VEC, as well as investigational agents and multiple randomized and non-randomized studies. The benchmark pathologic response rates with these agents range from 17% PCR with PD-1 monotherapy, 45% to 55% PCR with PD-1 CTLA-4 combination therapy, and slightly higher 57% PCR with PD-1 LAG-3 has recently reported by Dr. Rodabe Amaria from MD Anderson. However, as we embark on phase 3 comparisons for various neoadjuvant compared to adjuvant immunotherapy trials and combinations, we're increasingly moving towards event-free survival as the primary endpoint for neoadjuvant versus adjuvant studies. And this was most recently studied in the context of SWOG S1801, a study that was led by Dr. Sapna Patel.  So, Jason, before we start on NADINA, can you briefly summarize the SWOG S1801 trial and the event-free survival statistic reported by Dr. Patel and her colleagues? Dr. Jason Luke: Well, absolutely. And these data were reported at ESMO about two years ago and then in the New England Journal last year. The S1801 study answered a very simple question: What would happen if you took three of the doses of standard adjuvant therapy with pembrolizumab and moved them prior to surgery? And on a high level, the study is as simple as that. And many of us were somewhat skeptical of this trial design because we thought that just moving the doses earlier may not actually have a major impact.  In the study, you alluded to the event-free survival statistic, and that alludes to what was considered an event. And so, without reading all of it, there were several different aspects that were included in terms of time, based on the date of randomization until the first of a series of events, such as disease progression, toxicity from treatment, if the patient was unable to go to surgery or had surgical complications, or if they had delay in starting the adjuvant therapy due to toxicity, and obviously, recurrence of melanoma or death from any cause. In that context, merely moving the 3 doses of pembrolizumab to the neoadjuvant setting saw an improvement in this two-year event free survival to 72% for the neoadjuvant therapy compared to 49% for the adjuvant therapy. That was quite an outstanding change. And again, noting the power of neoadjuvant treatment, really dictating the impact of anti PD-1, again, just with 3 doses moving from adjuvant into the neoadjuvant setting, and I think all of us were somewhat surprised to see that magnitude of a benefit. But it set up the current study very well, where we now look at combination therapy. Dr. Diwakar Davar: So let's move on to the phase 3 NADINA trial. Do you want to perhaps discuss the study design, particularly focusing on the EFS primary endpoint and maybe also touching on the different schedules? So, SWOG S1801 was a neoadjuvant study of 3 cycles of pembrolizumab and how did that compare and contrast to the neoadjuvant combination that was studied in NADINA? Dr. Jason Luke: Well, as you alluded to, NADINA investigated the regimen of nivolumab plus ipilimumab and compared that against adjuvant therapy with nivolumab alone. So, in the study, as you alluded, the dose and schedule of the two drugs used was nivolumab at 3 milligrams per kilogram, and ipilimumab with 1 milligram per kilogram. That was based on a series of signal finding and safety studies that had been previously done by the same group of authors identifying that as the optimal treatment regimen. And it's worth noting that's slightly different than the labeled indication that's generally used for those same drugs for metastatic melanoma, albeit that the NCCN also endorses this schedule. So, in the trial, 423 patients were randomized, 1:1 to receive either neoadjuvant therapy with those 2 doses of nivolumab plus ipilimumab as compared with standard adjuvant therapy with nivolumab following surgery.   Now, one interesting tweak was that there was an adaptive nature to the study, meaning that patients had a fiducial placed at the index lymph node, and after the neoadjuvant therapy in that arm, that lymph node was removed. And if the patient had a major pathological response, they did not go on to receive the adjuvant portion of the treatment. So it was adaptive because those patients who did very well to the neoadjuvant did not require the adjuvant portion. And in those patients who did not achieve a major pathological response, they could go on to have the adjuvant therapy. And that also included the BRAF therapy for those whose tumors were BRAF mutants.  It's also worth pointing out that the definition of event free survival was slightly different than in the S1801 study that was alluded to just a second ago. And here, EFS was defined from the date of randomization until progression due to melanoma or due to treatment. So that's slightly different than the definition in the S1801 trial. So, a somewhat complicated study, but I really applaud the authors because I think this study does mirror what we would likely be doing in actual clinical practice.  Dr. Diwakar Davar: So, just to briefly summarize the efficacy, and then to get your comments on this, the path response, the PCR rate was 47%. The major pathologic response rate, which is the proportion of patients with between 0% to 1/10% of residual viable tumors, was about 12%. And for a major pathologic response rate of 0% to 10% of 59%. And then the rest of the patients had either pathologic partial response, which was 10% to 50%, or pathologic non response or 50% or greater residual viable tumor, all assessed using central pathology grades. The one year RFS was 95% in the FDR patient population versus 76% in the pathologic partial response patient population, 57% in the pathologic non response patient population. So how do you view these results? Can you context the FDR rates and the EFS rates from NADINA relative to nivo-rela and also potentially SWOG 1801? Dr. Jason Luke: Well, I think these are very exciting results. I think that for those of us that have been following the field closely, they're actually not especially surprising because they mirror several studies that have come before them. When we put them in context with other studies, we see that these rates of major pathological response are consistent with what we've seen in phase 2 studies. They're relatively similar. Or I should say that the results from nivolumab and relatlimab, which was also pursued in a phase 2 study of somewhat similar design, are somewhat similar to this. So, combination immunotherapy does look to deliver a higher major pathological response than pembrolizumab alone, as was known in S1801. Which of course, the caveat being is these are cross control comparisons that we need to be careful about. So I think all of these are active regimens, and I think adding a second agent does appear to enhance the major pathologic response rates. When we look at the event free survival, we see something similar, which is that numerically it looks to be that combination immunotherapy delivers a higher event free survival rate. And that looks to be rather meaningful given the difference in the hazard ratios that were observed between these various studies. And here in the NADINA study, we see that 0.3 hazard ratio for EFS is just extremely impressive.  So the abstract then, from ourselves, out of these specific studies, what does this mean more broadly in the real world, where patients exist and the rest of the landscape for clinical trials? I think we can't take enough time to stop for a second and just think about what a revolution we've come forward in with immune checkpoint blockade and melanoma. When I started my career, now, more than 15 years ago, melanoma was the cancer that made cancer bad. And now here we say, in the highest risk of perioperative patients, we can deliver 2 doses of nivolumab and ipilimumab, and essentially half of the patients then don't need to go on, and more than half the patients don't need to go on to have a full surgery and don't need adjuvant therapy. And from what we could tell of a very, very low risk of every heavy recurrence of melanoma. Of course, there's the other half of patients where we still need to do better, but these are just fantastic results and I think highly meaningful for patients.   In the context of ongoing clinical trials, another abstract that was presented during the meeting was the update to the individualized neoantigen therapy, or V940 with pembrolizumab or against pembrolizumab alone. That's the KEYNOTE-942 study. In that study, they presented updated data at two and a half years for relapse free survival, noting a 75% rate without relapse. So those results are also highly intriguing. And these are in a similar population of very high risk patients. And so I think most of us believe that neoadjuvant therapy with this study in NADINA is now confirmed as the priority approach for patients who present with high-risk stage 3 disease. So that would be bulky disease picked up on a scan or palpable in a clinic. I think essentially all of us now believe patients should get preoperative immunotherapy. We can debate which approach to take, and it may vary by an individual patient's ability to tolerate toxicity, because, of course, multi agent immunotherapy does have increased toxicity relative to anti PD-1 alone. But we'll have to wait now for the full phase 3 results from the V940 individualized neoantigen therapy. And if those come forward, that will be an extremely attractive approach to think about for patients who did not achieve a major pathological response to neoadjuvant therapy, as well as of course to the other populations of patients with melanoma where we otherwise currently give adjuvant therapy stage 2B all the way through stage 4 resected. It's an amazing time to think about perioperative therapy in melanoma. Dr. Diwakar Davar: So this is clearly outstanding data, outstanding news. Congratulations to the investigators for really doing what is an investigative initiated trial conducted across multiple continents with a huge sample size. So this clearly appears to be, at this point in time at least, a de facto standard. But is this going to be FDA-approved, guideline-approved, or is it possible in your mind? Dr. Jason Luke: Well, that's an interesting question. This study was not designed with the intent to necessarily try to register this treatment regimen with the FDA. One would have to take a step back and say, with how powerful these data appear, it sort of seemed like it would be too bad if that doesn't happen. But all the same, I think the community and those of us who participate in guideline recommendations are fully supportive of this. So, I think we will see this move into compendium listings that support insurance approval, I think, very, very quickly. So, whether or not this actually becomes formally FDA approved or is in the guidelines, I think this should become the standard approach that is considered for patients, again presenting with high-risk stage 3 disease.  Dr. Diwakar Davar: Fantastic. So now we're going to go in and talk about a slightly different drug, but also from the melanoma context, and that is the safety and efficacy of RP1 with nivolumab in the context of patients with melanoma who are PD-1 failures. So, this is Abstract 9517. And in this abstract, our academic colleagues essentially talked about these data, and we'll start by describing what RP1 is. RP1 essentially is a HSV-1 based oncolytic immunotherapy. And RP1 expresses GM-CSF as well as a fusogenic protein, GALV-GP-R-. And in this abstract, Dr. Michael Wong from MD Anderson and colleagues are reporting the results of IGNYTE, which is a phase I trial of intratumoral RP1 co-administered with systemic nivolumab in patients with advanced metastatic treatment refractory cutaneous melanoma. And the data presented in this abstract represents data from a registration directed, abbreviated as RD, registration directed cohort of RP1 plus nivolumab in PD-1 refractory melanoma. So, let's start with the description of the cohort.  Dr. Jason Luke: Right. So, in this study, there were a total of 156 patients who were presented, and that included an initial safety and dose finding group of 16, as well as the RD cohort, as you noted, of 140 patients. And it's important to point out that this was a cohort that was selected for a very strict definition of progression on anti PD-1, or a combination immunotherapy as their immediately prior treatment. So, all of the patients in the cohort had exposure to anti PD-1, and 46% of them had anti PD-1 plus anti CTLA4, nivolumab and ipilimumab as their immediately prior therapy. This was also a group of relatively high-risk patients when one considers stage. So, within the stage 4 population, the entry here included 51% who had stage M1B, C, and D melanoma. And that is worth pointing out because this is an injectable therapy. So, trials like this in the past have tended to be biased towards earlier stage, unresectable or metastatic melanoma, meaning stage 3B, 3C, 3D and then stage 4m1a. Again, to emphasize the point here, these were pretreated patients who had a strict definition of anti PD-1 resistance, and over half of them, in fact, had high-risk visceral metastatic disease.  In that context, it's very interesting to observe that the overall response rate was described in the total population, as 31%, and that included 12% who achieved complete response. And so, again, to make sure it's clear, we're talking about a treatment where the oncolytic virus is injected into one or multiple sites of recurrent disease, and then the patients administer nivolumab as per standard. And so, I think these data are quite intriguing. Again, such a high- risk population and their maturity now, with a follow-up of over a year, I think, makes this look to be a very interesting treatment option.  Dr. Diwakar Davar: I guess on that topic of mature follow-up, it probably would be important for us to inform our audience that the top line data for the primary analysis was actually just released, I think, earlier today, and wherein the central confirmed objective response rate was 34% by modified RECIST and 33% by RECIST, clearly indicating that these responses, as you noted, very treatment refractory patient population, these responses were clearly very durable. So, you mentioned that there were responses seen in uninjected visceral lesions, responses seen in both PD-1 and PD-1 CTLA-4 refractory patients. Can you talk a little bit about the response rate in these high-risk subgroups, the uninjected visceral lesions, the patients who had both combination checkpoint and epidural refractory response rate by primary PD-1 resistance.  Dr. Jason Luke: Sure. You know, I think, again, to emphasize this point in the study, we saw that there were responses in the non-injected lesions, and I think it's really important to emphasize that. Some have referred to this as a putative abscopal like effect, similar to what is described in radiation. But it implies that local treatment with the oncolytic virus is triggering a systemic immune response. In the higher risk patient population, we'll note that whereas the overall response rate in PD-1 refractory patients was 34%, in the combination of PD-1 and CTLA-4 refractory patients, the response rate was 26%. So, [this is] still very good. And when we looked at that split by stage, as I alluded to before, in the population of patients that had, what you might call earlier unresectable diseases, so 3B through 4A, the response rate was 38%, and in the stage 4 M1b through M1d, it was 25%. So slightly lower, but still very good. And that would be as expected, because, of course, the patients with visceral metastatic disease have more advanced disease, but those response rates look quite good. Again, looking at the combination refractory population as well as the more high-risk disease. Dr. Diwakar Davar: So, clearly, these are very promising data and exciting times for multiple investigators in the field and the company, Replimune, as well. So, what are the next steps? I believe that a registration trial is planned, essentially, looking at this with the goal of trying to get this combination registered. Can you tell us a little bit about IGNYTE-3, the trial design, the control arm, and what you foresee this trial doing over the next couple of years?  Dr. Jason Luke: So, as this agent has been maturing, it's worth pointing out that the company that makes this molecule, called RP1, but I guess now we'll have to get used to this name vusolimogene oderparepvec as the actual scientific term, they have been having ongoing discussions with the FDA, and there is the potential that this agent could come forward on an accelerated path prior to the results being released from a phase 3 trial. That being said, the phase 3 confirmatory study, which is called the IGNYTE-3 study, is in the process of being launched now. And that's a study investigating this molecule in combination with nivolumab, as was alluded to earlier, and a randomized phase 3 design, where that combination is compared with a physician's choice, essentially a chemotherapy-based option.   In that study, it will be 400 patients with stage 3B through stage 4; patients will have progressed on anti PD-1, either as a combination or in sequence, and then come on the study to be randomized to either vusolimogene oderparepvec plus nivolumab versus that physician's choice. And the physician's choice includes chemotherapy agents, but also nivolumab plus relatlimab as another option, or an anti PD-1 monotherapy, if that's deemed to be a reasonable option by the treating investigator. And the primary endpoint of that study is overall survival. And unfortunately, in this highly refractory patient population, that's something that may not take long to identify with key secondary endpoints of progression free survival, as well as overall response rate. I'm quite enthusiastic about this study, given these data, which have now been centrally confirmed as you alluded to before. I think this is a very exciting area of investigation and really crossing my fingers that this may be perhaps the first locally administered therapy which does appear to have a systemic impact that can hold up in phase 3. Dr. Diwakar Davar: Very, very, very exciting results. And I guess it's worthwhile pointing out that this company also has got, I think, multiple studies planned with both RP1 and cutaneous squamous cell carcinoma in a solid organ transplant patient population where single agent activity has already been reported by Dr. Migden at prior meetings, as well as a novel trial of potentially RP2 metastatic uveal melanoma. So we'll now pivot to Abstract 6014. So, 6014 is a drug by a company known as Merus. Essentially, it's a very novel agent. Merus essentially is a company that is specialized in making bicyclics and tricyclics. And these are not bicycles or tricycles, but rather drugs that essentially are bispecific antibodies. And Merus essentially has come up with petosemtamab. I think we're going to have to figure out better names for all of these drugs at some point. But petosemtamab, or MCLA-158, essentially is a bicyclic, targeting both EGFR as well as LGR-5. So EGR-5, of course, is a known oncogenic driver in multiple tumor types, squamous, including non small cell lung cancer, cutaneous squamous cell carcinoma, but also head and neck squamous cell carcinoma. And LGR-5 essentially is leucine-rich repeat-containing G-protein coupled receptor 5, but it's a receptor in cancer stem cells and certainly highly expressed in head neck squam. And MCLA-158, or petosemtamab is a IgG one bispecific with ADCC-activity because of IgG1 backbone co-targeting EGFR and LGR5. Merus had earlier results that evaluated petosemtamab monotherapy. They defined the RP2D and second- and third-line head and neck blastoma patients with a respectable response rate of 37% investigator-assessed ORR with six months median DoR, and this was published by Ezra Cohen about a year or so ago.  In this abstract, Dr. Fayette and colleagues report on the results of the MCLA-158-CL01 trial, which is a trial of pembrolizumab plus petosemtamab in one front line head and neck squamous cell population. So maybe let's start with the description of the cohort. And it is a small trial, but we'll be able, I think, to dig into a little bit about why this might be exciting. Dr. Jason Luke: Yes. So, as alluded to, it's not the biggest trial as yet, but there were 26 patients with anti PD-1 treatment naive head and neck squamous cell carcinoma. And all the patients in the study did receive, as you alluded to, pembrolizumab plus petosemtamab. Based on the label for pembrolizumab, all the patients in this study were PDL-1 positive. So that's one point that it's worth pointing out to make sure that that's understood. This is the population of patients who would be expected to benefit from pembrolizumab in the first place. Now, in the abstract, they reported out only 10 response evaluable patients, but they updated that in the actual slides of presentation at the meeting. So among 24 patients that were alluded to, 67% were described as having had a response, although some of those were yet to be confirmed responses. And when it was evaluated by PDL-1 status, there didn't seem to be a clear enrichment of response in the PD-1 positive more than 20% group, as compared to the 1-19% group. That isn't especially surprising because that was a trend that one would see, presumably with pembrolizumab alone. But overall, I think these data are pretty exciting in terms of a preliminary study. Dr. Diwakar Davar: You know, you mentioned that the objective response rate was high, almost 60-something%. The prognosis of these patients is generally poor. The OS is typically thought of as between 6-15 months. And based on KEYNOTE-048, which was led by Dr. Burtness and colleagues, the standard of care in the setting is pembrolizumab +/- platinum based chemotherapy regimens. Allowing for the fact that we only have 10 patients here, how do you think these results stack up against KEYNOTE-048? And you made a very important point earlier, which was, by definition, pembro is on label only for the CPS. So PDL-1 score, at least in head and neck squamous cell carcinoma CPS and not TPS. But in the CPS 1% or greater patient population, where pembro is on label, how do these results stack up against the KEYNOTE-048 results. Dr. Jason Luke: Right. KEYNOTE-048 is considered the seminal study that dictates frontline treatment in head and neck cancer. And before we dive into this too far, we do want to acknowledge that here we're comparing 26 patients versus a phase 3 trial. So, we're not trying to get too far ahead of ourselves, but this is just a preliminary comparison. But in KEYNOTE-048, as you alluded to, two regimens were superior to chemotherapy. One was the pembrolizumab monotherapy, as well as pembrolizumab plus chemotherapy. So again, the study overall survival, of course, was much higher, the PDL-1 positive subgroup, which is what dictated the unlabeled use of this. But response to pembro monotherapy in that population of patients is still modest. We're talking about upwards of 20-30%. So, if you compare that to, again, preliminary evidence here from this trial of only 24 patients, that response rate of 60% seems extremely high. And so even if that were to come down somewhat in a larger data series of patients, that still looks to be quite promising as a treatment regimen, that might eventually even be chemotherapy sparing for this population of patients. I think this raises a lot of eyebrows that perhaps this dual targeting approach, EGFR and LDR-5, may bring something really important to the field that evolves it. Dr. Diwakar Davar: So, what are the next steps for petosemtamab? You mentioned that the activity was interesting. Are we going to see a larger trial? Any thoughts on where things are going to go?  Dr. Jason Luke: Well, based on the phase 2 data of petosemtamab alone, even without pembrolizumab, the molecule had already been given fast track designation by FDA, which means allowing for greater communication between the drug sponsor in the FDA and designing a seminal study design. One would assume that this trial will be rapidly expanded quite greatly, perhaps to 100 or 200 patients, to try to flush out what the real response rate is in a more meaningful number of patients. But I think these data will probably also trigger the design and probably near-term evaluation or expedited acceleration of a phase III clinical trial design that would potentially validate this against the current standard of care. So, I'm pretty excited. I think we'll see a lot more about this agent in the relatively near future. Dr. Diwakar Davar: So, finally, we'll pivot to the last abstract that we're going to talk about, which is Abstract 2504. It's a relatively interesting target, CCR8 monoclonal antibody. But this is the efficacy and safety of LM-108, and LM-108 is an anti CCR8 monoclonal antibody that is being developed by LaNova Medicine. And the results that are described, actually a pool set of results of combinations of LM-108 with anti PD-1, two separate anti PD-1, in patients with gastric cancer, mostly done ex-U.S., which is interesting because of this patient population, and it's a pool result of several, 3 phase 1 and 2 studies.  LM-108 is an Fc-optimized anti CCR8 monoclonal antibody that selectively depletes tumor infiltrating Tregs. The abstract reported a pooled analysis of three phase 1, 2 trials with 3 different NCT numbers that all evaluated the efficacy of LM-108 and anti PD-1 in patients with gastric cancer. So, let's start with the description of the cohort. Maybe, Jason, you can tell us a little bit about before you start, as you describe the cohort, sort of what we know, editorially speaking, about the difficulty with which Tregs depletion has been tried and obviously failed up until now in the tumor microenvironment. Dr. Jason Luke: Right. I think that's a really interesting comment. And so, for decades, in fact, targeting regulatory T-cell to alleviate immune exclusion in the tumor microenvironment has been of interest in immuno-oncology. And in preclinical mouse models, it seems quite clear that such an approach can deliver therapeutic efficacy. However, by contrast, in human clinical trials, various different Treg depleting strategies have been attempted, and there's really little to no evidence that depleting Tregs from human tumors actually can deliver therapeutic responses. And by that we're referring to CD-25 antibodies. The drug ipilimumab, the CTLA-4 antibody, was punitively described as a Tregs depleter preclinically, but that doesn't seem to be the case in patients. And so, in that background, this is quite an eye raiser that an anti CCR8 antibody could be driving this effect. Now, before we talk about the results of this trial, I will point out, however, that given the Fc-optimization, it's entirely possible that the Tregs are being depleted by this mechanism, but that more could also be going on. Because Fc gamma RII binding by this antibody that could be nonspecific also has the potential to trigger immune responses in the tumor microenvironment, probably mediated by myeloid cells. So I think more to come on this. If this turns out to be the first meaningful Tregs depletor that leads to therapeutic efficacy, that would be very interesting. But it's also possible this drug could have multiple mechanisms.  So, having said all of that, in the clinical trial, which was a pooled analysis, like you mentioned, of LM-108 in combination with anti PD-1 of a couple different flavors, there were 48 patients treated either with LM-108, with pembrolizumab, or with toripalimab, which is another anti PD-1 antibody. On the drug combination was, generally speaking, pretty well tolerated, noting grade 3 treatment related adverse events in the range of 38%, which is somewhat expected given combination immunotherapy. We talked about nivolumab and ipilimumab before, which, of course, gives even higher rates of immune-related adverse events, with the most common toxicities being anemia, lipase elevations, rash, ALC decrease; albeit, quite manageable. Dr. Diwakar Davar: So, what about the objective response rate? Can you contextualize the efficacy? And as you do that, maybe we'll think about what you'd expect in the context of, say, gastric cancer, especially in patients who've never really had a prior checkpoint inhibitor before. What do you think about the ORR? What do you think about the relative efficacy of this combination? Dr. Jason Luke: Well, so, in the study, they described overall response rate in the 36 patients as 36% and described immediate progression for survival of about 6.5 months. And so that was among patients who were treatment naive. And in second-line patients, they actually described an even higher response rate, although it was only 11 patients, but they're at 64%. And so, I think those data look to be somewhat interesting. When I was actually scrutinizing the actual data presented, it was of some interest to note that the quality of responses seemed to be about as good on the lower dose of LM-108, so 3 milligrams per kilogram as compared to 10 milligrams per kilogram. I think there's definitely more to learn here to try to optimize the dose and to fully understand what the overall efficacy of this treatment combination would be.  I would emphasize that in this disease, I think novel treatment strategies are certainly warranted. While anti PD-1 with chemotherapy has moved the needle in terms of standard of care treatment, it's really only a minor subset of patients who derive durable long-term benefit like we normally associate with immune checkpoint blockade. I think these are preliminary data. They're very intriguing.   You alluded to earlier that this population of patients was an Asian data set, and it is well known that the efficacy of chemotherapy and immunotherapy does appear to be somewhat enhanced in Asian populations, and that goes to distributions of metastasis and tumor microenvironment effects, etc. Very difficult to try to tease any of that out in this abstract, other than to look at these data and suggest that this is pretty interesting, both from a novel therapeutic approach, we talked about the Tregs consideration, but also straight up on the efficacy because I think if these data could hold up in a larger number of patients, and particularly in a western population of patients, I think it would be very intriguing. Dr. Diwakar Davar: Certainly, ASCO 2024 had a lot of interesting data, including data from targeted agents, the LAURA trial, ADCs. But just focusing on the immune therapy subset, we certainly saw a lot of great advances in patients who were treated with neoadjuvant as well as relapse refractory disease in the context of RP1 and then a couple of newer agents such as this petosemtamab as well as LM-108. And of course, we cannot forget to highlight the extended DMFS data from the pembro vaccine study from KEYNOTE-942.  Jason, as always, thank you for taking a little bit of time out of your extremely busy schedule to come and give us insights as to how these agents are impacting the landscape. We really value your input and so thank you very much.  Dr. Jason Luke: Thank you for the opportunity. Dr. Diwakar Davar: And thank you to our listeners for your time today. You will find the links to all the abstracts that we discussed in the transcript of this episode. And finally, if you value the insights that you hear on this podcast, please take a moment to rate, review and subscribe wherever you get your podcasts. So, 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. Diwakar Davar   @diwakardavar   Dr. Jason Luke   @jasonlukemd      Follow ASCO on social media:    @ASCO on Twitter   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

"Here at last, at the edge of the sea, comes the end of our Fellowship." So said Gandalf the White at the conclusion of J.R.R Tolkien's epic The Lord of the Rings. Today, Josh and Michael have a no less epic conclusion to their own adventure, that of ASCO 2024. Over the last fifteen days, our intrepid hosts have journeyed across the world of medical oncology, from the highs of colorectal, breast and lung cancer to the dark days of central nervous system tumours. As is our tradition, we end our coverage with a look at the studies chosen by the ASCO committee as worthy of special attention: the plenary presentations. It is rare indeed to have four presentations in one year that all change clinical practice, but that is what we have been treated to this year.Thank you for joining us for coverage of ASCO 2024; we have enjoyed ourselves immensely in covering it, and we hope you have enjoyed our meandering journey through some of the best oncology researchers in the world. We will be back in a couple of weeks as Oncology for the Inquisitive arm returns to its normal programming.Links to studies discussed in this episode (subscription may be required): ESOPEC: LinkNADINA: LinkLAURA: LinkADRIATIC: LinkFor more episodes, resources and blog posts, visit www.inquisitiveonc.comPlease find us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comOncology for the Inquisitive Mind is recorded with the support of education grants from Pfizer, Gilead Pharmaceuticals and Merck Pharmaceuticals. Our partners have no editorial rights or early previews, and they have access to the episode at the same time you do.Art courtesy of Taryn SilverMusic courtesy of AlisiaBeats: https://pixabay.com/users/alisiabeats-39461785/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice. Hosted on Acast. See acast.com/privacy for more information.

When the immune checkpoint inhibitor durvalumab was added to standard-of-care chemoradiation treatment for patients with limited-stage small-cell lung cancer, it brought a “statistically significant and clinically meaningful” improvement in overall and progression-free survival, compared to adding placebo. This was in data from the ADRIATIC study reported in the Plenary Session at the 2024 ASCO Annual Meeting in Chicago. Peter Goodwin was there for Oncology Times, where he talked with the lead author of the new research, David Spigel, MD, Chief Scientific Officer at Sarah Cannon Research Institute in Nashville, TN.

Critical Appraisal - My 2 hour ASCO lecture - Day 2 version by Plenary Session

Drs. Vamsi Velcheti and Nathan Pennell discuss key lung cancer abstracts from the 2024 ASCO Annual Meeting, including data from LUMINOSITY and ADAURA, novel therapies in KRASG12C-mutant advanced NSCLC, and the need for effective adjuvant therapies for patients with rare mutations. TRANSCRIPT Dr. Vamsi Velcheti: Hello, I am Dr. Vamsi Velcheti, your guest host for the ASCO Daily News Podcast today. I'm a professor of medicine and director of thoracic medical oncology at Perlmutter Cancer Center at NYU Langone Health. Today, I'm delighted to welcome Dr. Nathan Pennell, the co-director of the Cleveland Clinic Lung Cancer Program and vice chair of clinical research at the Taussig Cancer Center. Dr. Pennell is also the editor-in-chief of the ASCO Educational Book. Dr. Pennell is sharing his valuable insights today on key abstracts in lung cancer that will be presented at the 2024 ASCO Annual Meeting. You'll find our full disclosures in the transcript of the episode.  Nate, it's great to have you here on the podcast. Thank you for being here. Dr. Nathan Pennell: Thanks, Vamsi, for inviting me. I'm always excited for the ASCO Annual Meeting, and we have a tremendous amount of exciting lung cancer abstracts. I know we're not going to discuss all of them on this podcast, but even exciting Plenary presentations coming up.  Dr. Vamsi Velcheti: So, one of the abstracts that caught my attention was Abstract 103, the LUMINOSITY trial, which will be presenting the primary analysis at the meeting. So, there's a lot of buzz and excitement around ADCs. Can you comment on this abstract, Nate, and what are your thoughts on key takeaways from this abstract?  Dr. Nathan Pennell: Absolutely, I agree. This is really an exciting new potential target for lung cancer. So historically, when we think about MET and lung cancer, we think about the MET exon 14 skipping mutations which are present in 3% or 4% of adenocarcinoma patients. And we have approved tyrosine kinase inhibitors, small molecule inhibitors that can be very effective for those. What we're talking about here is actually an antibody drug conjugate or ADC telisotuzumab vedotin, which is targeting the MET protein over expression in non-squamous EGFR wild type advanced non-small cell lung cancer. The LUMINOSITY was a single arm, phase 2 study of teliso, and first of all, I think we have to define the patient population. So, these were MET over expressing non-small cell lung cancer by immunohistochemical staining. So, it included both what they considered MET high expression and MET intermediate expression, both of which had to be 3+ IHC positive on 25% to 50% of cells in the intermediate and 50% or higher in the high expressing group. They were treated with the ADC and had pretty promising results, a response rate of 35% in the MET high group and 23% in the intermediate group. Duration of response at nine months and 7.2 months in those two groups, and the PFS was five and a half and six months. So I would say in a previously treated population, this was relatively promising and potentially defines a completely new and unique subgroup of biomarker defined patients. So, Vamsi, I'm curious, though, if this ends up moving forward to further development, what your thoughts are on adding yet another biomarker in non-small cell lung cancer? Dr. Vamsi Velcheti: Yeah, I think it's certainly exciting. I think for this population, we really don't have a lot of options beyond the second line, and even in the second line, docetaxels are low bar. So,I think having more options for our patients is certainly outcome development. And I think MET IHC is relatively easy to deploy in a clinical setting. I think we already test for MET PD-L1 IHC routinely, and now recently, as you know, HER2 IHC given approval for ADCs, HER2 ADCs there in that space. So, I think from a technical standpoint, I don't see a big barrier in terms of adding an additional IHC marker. And usually, the IHC testing is pretty quick. And I think if you have a therapeutic approval based on IHC positivity, I think certainly from an operational standpoint, it shouldn't be a very complicated issue. Dr. Nathan Pennell: Yeah, I agree. This is cheap. It's something that can be done everywhere in the world. And as you said, in addition to diagnostic IHC, we're already looking at PD-L1, and probably moving towards doing that for HER2. This is really wonderful that we're moving into kind of the era of the ADCs, which is opening up a whole new therapeutic group of options for patients. Dr. Vamsi Velcheti: So, the other abstract that caught my attention was like, the Abstract 8005. This is the molecular residual disease MRD analysis from the ADAURA trial. The ADAURA trial, as you all know, is the trial that led to the FDA approval of adjuvant use of osimertinib in patients with EGFR mutant stage 1B through 3A non-small cell lung cancer. And in this trial, osimertinib demonstrated significant improvements in DFS and OS. And in this particular study, Abstract 8005, the authors looked at the role of MRD in predicting DFS in the study. And after 682 patients who were randomized, 36% of the patients had samples to look at MRD post- surgery. And in the trial the MRD status predicted DFS or event free survival at 36 months with a hazard ratio of 0.23. And the MRD status had a median lead time of 4.7 months across both the arms, both osimertinib and the placebo arm. So, suggesting that MRD could potentially identify high risk subgroups of patients post-surgery to tailor personalized approaches potentially in this population. So, Nate, in your practice, of course, we don't have a clinically validated approach yet to kind of use MRD in this setting, but if we have an option to use an MRD based assay, do you think that would potentially be an opportunity to perhaps escalate or de-escalate adjuvant strategies with TKIs in the adjuvant setting? Do you see value in using MRI assays post- surgery? Dr. Nathan Pennell: Yeah, I think this is a really important study because this is such an important topic around adjuvant targeted treatment. So, of course, ADAURA really changed how we treated people with EGFR mutant lung cancer who underwent surgical resection, because we know that the three years of osimertinib significantly improved disease-free survival and overall survival. But there's still a lot of questions being asked about, is that affordable? Obviously, we're putting a lot of resources into three years of treatment, and not everyone necessarily needs it. There may well be people who are cured with surgery alone and adjuvant chemotherapy. And then what about duration? Is three years enough? Do we need even longer treatment, or do we need shorter treatment? And up to date, we haven't really been able to tell people at risk of recurrence other than the pure odds-based risk based on their stage.   And the assay that was used in the ADAURA study was a personalized tumor informed assay based on the resected tumor. It's unclear to me whether this was just a subgroup of people that had this done or whether they tried to do it in all 600 patients and only, it looks like they were successful in about 32% of people. Maybe about a third were able to successfully have a tumor informed assay. So, the first question is, “Can you use this to help guide who needs treatment or not?” And I think what they showed was only about 4% of people in osimertinib arm in 12% had MRD positive at baseline after surgery. So probably, upfront testing is not really going to be all that helpful at determining who's at high risk and needs to be treated.   Interestingly, of those who were positive, though, most of them, or 80% of them, did go MRD negative on osimertinib. And what I found really interesting is that of those who did have a recurrence, 65% of them did have the MRD test turn positive. And as you mentioned, that was about five months prior to being picked up radiographically, and so you can pick them up sooner. And it also looks like about two thirds of recurrences can be identified with the blood test. So that potentially could identify people who are recurring earlier that might be eligible for a more intensive treatment. The other thing that was really interesting is of those who recurred in the osimertinib arm, 68% of them happened after stopping the osimertinib, suggesting that for the majority of patients, even those not necessarily cured, they seem to have disease control while on the osimertinib, suggesting that maybe a longer duration of treatment for those patients could be helpful. The problem is it still isn't necessarily helpful at identifying who those people are who need the longer duration of treatment. So, definitely an important study. I think it could be useful in practice if this was available clinically, especially at monitoring those after completion of treatment. I think as the sensitivity of these MRD assays gets better, these will become more and more important. Dr. Vamsi Velcheti: I think it's a little bit of a challenge in terms of standardizing these assays, and they're like multiple assays, which are currently commercially available. And I think the field is getting really complicated in terms of how you incorporate different assays and different therapeutics in the adjuvant space, especially if you're kind of looking at de-escalating immunotherapeutic strategies at the adjuvant setting, I think, makes it even more challenging. I think exciting times. We definitely need more thoughtful and better studies to really define the role of MRD in the adjuvant space. So, I guess more to come in this space. Dr. Nathan Pennell: Vamsi, I wanted to ask you about another really interesting Abstract 8011. This is a subgroup of the AEGEAN perioperative study for early-stage resected non-small cell lung cancer. This abstract is specifically looking at baseline N2 lymph node involvement in stage 2A-3B with N2 positive patients in an exploratory subgroup analysis. What are your key takeaways from the study?   Dr. Vamsi Velcheti: I felt this was a very interesting abstract for a couple of reasons. As you know, this is the AEGEAN trial, the phase 3 trial that was reported earlier last year. This is a perioperative study of durvalumab plus new adjuvant chemotherapy versus new adjuvant chemotherapy alone and adjuvant durvalumab plus placebo. The study obviously met its primary endpoint, as we all saw, like the event-free survival. And here in this abstract, the authors present an exploratory subgroup analysis of patients who had N2 lymph node involvement prior to study enrollment. So, in this study, they were focusing on perioperative outcomes. And one of the issues that has come up multiple times, as you know, in a lot of these preoperative studies, is the impact of neoadjuvant chemo immunotherapy on surgery or surgical outcomes. And consistently, across a lot of these trials, including the CheckMate 816, about 20% of patients don't end up making it to surgery. So in that light, I think this study and the findings are very interesting. In this study, they looked at patients who had N2 nodal involvement and of the patients with N2 nodal involvement, the surgical operability or the number of patients who completed surgery was similar in both the groups. So, there was no significant difference between patients who received durva versus chemotherapy and also among patients who had N2 subgroup who had surgery, similar proportions of durvalumab and placebo arms had open versus minimally invasive versus pneumonectomy. So durvalumab didn't have a negative impact on the type of surgery that the patients had at the time of surgery. So overall, the findings were consistent with other trials, perioperative trials that we have seen. So, the surgical outcomes were not negatively impacted by adding immunotherapy in the neoadjuvant perioperative space. So, this is consistent with other trials that we have seen. And also, the other issue, Nate, I'd like to get your opinion on is, across the board, in all the perioperative trials we have seen that about 20% of the patients actually don't end up making it a surgery. And of course, most of these perioperative trials, a lot of these patients are stage 3 patients. And my take on this was that there's probably a little bit of a patient selection issue. We generally tend to err on the side of operability when we have a stage 3 patient discussed in the tumor board, sometimes feel like the patient may downstage and could potentially go to surgery. But even in the real world, in stage 3 operable patients, what proportion of patients do you think don't end up going to surgery? Dr. Nathan Pennell: That is such an important question that I don't think we have the best answer to. You're right. All of these perioperative studies have a relatively high- sort of 20% to 30% of people who enroll on the studies don't necessarily go to surgery. And I don't think that they've done as great a job as they could in all of these trials describing exactly what happens to these patients. So in the real world, obviously not everyone would be fit enough to go to surgery or might progress in the time between when they were diagnosed and the time as planned for surgery. But probably more of them would go to surgery if they weren't getting neoadjuvant treatment, because that would be their initial treatment. The question is, of course, is that the right choice? If someone gets 12 weeks or nine weeks of neoadjuvant treatment and then a restaging scan shows that they've had progression with metastatic disease, are those really the people that would have been optimally treated with surgery upfront, or would they just have had recurrence on their first postoperative scan? So, it's really an important question to answer. I think the bigger one is, is the treatment preventing them through toxicity from going to treatment? And I think the studies have generally felt that few patients are missing out on the option of surgery because of toxicity being caused by the IO. And in the AEGEAN study, for example, in this subgroup, a slightly numerically higher percentage of patients in the durvalumab arm actually underwent surgery compared to those who got neoadjuvant chemo. So, it doesn't seem like we're necessarily harming people with the neoadjuvant treatment. But I know that this is a concern for patients and doctors who are undergoing this approach. Dr. Vamsi Velcheti: Definitely, I think having multiple data sets from perioperative trials, looking at the relative impact of IO on the safety and the nature of the surgery is going to be important, and this is a very important study for that reason. Dr. Nathan Pennell: Can I ask you another thing that I thought really interesting about this particular one is they looked at the difference between those with single station N2 and multi station N2. And I know this is one of those, should we be operating on people who have multi station N2 disease? And the AEGEAN study did include people who had multiple N2 stations where perhaps in the pre-IO era, these would have been treated with definitive chemoradiation and not surgery at all. But the disease-free survival hazard ratio was essentially the same for multi station N2 as it was in the overall population. So, has that changed the way we're approaching these patients in these multidisciplinary discussions? Dr. Vamsi Velcheti: Absolutely, Nate. I think surgical operability is in the eye of the beholder. I think it depends on which surgeon sees the patient or how the discussion goes in the tumor boards, as you know. Certainly, I think with this optionality of having a chemo IO option and potential for downstaging, kind of pushes, at least in our practice, more of these patients who are multistation, who would have otherwise gone down the chemoradiation route are now actually going through neo adjuvant chemo IO and with the hope that they would make it to surgery. So, I think it's an interesting change in paradigm in managing our locally advanced patients. So, I think it's certainly interesting, but I guess to your point, there clearly are some patients who probably should just have chemoradiation upfront, and we may be kind of like delaying that definitive chemoradiation approach for at least a subset of patients. So, at the end of the day, I think it's a lot of clinical decision-making and I think there's going to be a little bit of art to managing these patients and it's going to be really hard to define that population for a clinical trial.  Dr. Nathan Pennell: Yeah, clearly, multidisciplinary discussion, still very important for earliest age non-small cell lung cancer patients. If we move back to metastatic lung cancer, let's talk about Abstract 8510 looking at one of our newer, exciting biomarkers, which are the KRASG12Cmutant non-small cell lung cancer. So this is a study of a second generation KRASG12Cinhibitor, olomorasib, which was combined with pembrolizumab, the anti PD-1 antibody, in patients with advanced KRASG12C mutant non-small cell lung cancer. This is something that has been tried before with first generation G12C inhibitors, with some concerns about how safe it was to do that. So, Vamsi, what did you learn from this abstract? Dr. Vamsi Velcheti: Definitely, I think one of the concerns that we've had in other trials is like the cumulative toxicity of adding checkpoint inhibition to G12C inhibitors, especially the sotorasib CodeBreaK trial, where we see increased rates of grade 3, 4 transaminitis. So, it is encouraging to see that some of the newer agents have less of those issues when it comes to combining the checkpoint inhibition. So especially with KRASG12C, as you know, these are patients who are smokers, and often these are patients who have high PDL-1 could potentially also benefit from immunotherapy. In order for these KRASG12C inhibitors, in order to move these targeted therapy options for these patients to the front line, I do think we need to have substantial comfort in combining the checkpoint inhibitors, which is a standard treatment approach for patients in the frontline setting. I think this is exciting, and I think they're also like, as you know, there are other KRASG12C inhibitors also looking to combine with checkpoint inhibition in the frontline settings. So, we'll have to kind of wait and see how the other agents will perform in the setting. Dr. Nathan Pennell: Yeah, I completely agree. I think this is such an important area to explore specifically because unlike our other targeted oncogenes like EGFR and ALK, we have multiple options for these patients, both immunotherapy and targeted treatments. And if we could think about sequencing them or even combining them and if it could be done safely, I think that would be well worth investigating. There still was significant toxicity in this trial; 30% of people had diarrhea, even at the reduced dose, and there was transaminitis at sort of about 20% or so, although probably at a manageable level. But the response rate was really quite promising. And these are all previously IO and mostly G12C TKI pre-treated patients still had a response rate of 63%. And in those who were naive to IO and TKIs, it was 78% response rate. So, if it could be done safely, I think it's definitely worth pursuing this in further trials. Dr. Vamsi Velcheti: And also, there's some data, preclinical data, like looking at G12C inhibition. And also we have known with MET inhibition for a long time that it could potentially augment immune responses and could be having some synergistic effect with IO. So, we'll have to wait and see, I think. But safety is really the top in mind when it comes to combining these agents with checkpoint inhibitors. So, it's really encouraging to see that some of the newer agents may be more combinable IO. Now moving on to the next abstract, and moving on to, again, the early-stage setting. So, Abstract 8052 from our colleagues in Princess Margaret reported outcomes in early-stage non- small cell lung cancer in patients with rare targetable mutation. This is actually becoming increasingly more relevant because we are seeing at least, like with the ALINA data, with the ALK and EGFR, now with ADAURA, we know that these patients don't benefit with adjuvant immunotherapy, especially some of these rare oncogene living mutations, other than like G12C. So I always struggle with this. When you have early-stage patients, with, let's say, a ROS or a RET, where we just don't have data, and we know that those are poor actors because biologically these are aggressive tumors. So, there's a really odd clinical question to ask in terms of, what is the role of adjuvant immunotherapy? Of course, this trial and this abstract are not really addressing that. But what is your take on this abstract? If you could just summarize the abstract for us. Dr. Nathan Pennell: Sure. Well, I think this is incredibly important, and this is an area near and dear to my own heart. And that is, of course, the whole landscape of how we manage early-stage patients has changed with both ADAURA, because we now have effective treatment in the adjuvant setting for EGFR mutant patients, and now more recently with the ALINA trial for adjuvant alectinib for ALK positive patients now being FDA-approved. So, what that means is we actually have to be testing people at diagnosis even before they would be getting adjuvant treatment, and potentially before even surgery to look for these targets. We need the PD-L1 status, we need EGFR and ALK. And if you're going to be looking at these biomarkers, I think there is a reasonable argument to be made that you should be doing broad testing for all of the targetable oncogenes in these patients. There are some studies suggesting that there's value to this and identifying them for treatment at the time of recurrence. But we also know that these patients are at high risk of recurrence and probably need to be investigated, at least in trials for the adjuvant setting. So, this particular study looked at 201 resected, mostly adenocarcinoma patients, and then they basically sequenced them for all of the targeted oncogenes. And they were quite common, perhaps even more common than you might expect in an advanced population. So, 43% of them had KRASG12C mutations, 13% had EGFR Exon 20 mutation, ERBB2 or HER2 mutations found in 11%, MET mutations in 10%, ALK in 7%, ROS1 in 6%, BRAF in 5%, and RET in 2%. So quite common to find these targetable oncogenes in this particular population, perhaps a somewhat biased population at Princess Margaret Hospital, but very common. And then they looked at the outcomes of these patients without targeted adjuvant treatment. And what they found was there was a very high rate of recurrence. So, relapse-free survival was pretty high in these patients across different stages, and generally their prognosis was worse than the more common KRASG12C patients. Most of these, in particular the HER2 mutant patients, seem to have a significantly worse relapse free survival. Interestingly enough, though, that did not carry over to overall survival. Overall survival was better in those who had targetable oncogenes. And my guess is that that probably had to do with the availability of targeted treatments at the time of recurrence that may have impacted overall survival. But I do think that this particularly highlights the need, the unmet need for effective adjuvant treatment in these patients. And most of them, with the exception of KRAS and perhaps BRAF, perhaps MET unlikely to benefit from adjuvant immunotherapy, as you mentioned. And so, I think we really need to be investing in trials of adjuvant targeted treatments in these populations.  Dr. Vamsi Velcheti: Yeah, this is an area that we really don't have a lot of data. But Nate, a question for you. So tomorrow you have a patient with RET fusion, stage 2, N1 disease. What would you do? Would you offer them an adjuvant RET inhibitor? Dr. Nathan Pennell: I think I would search really hard for a trial to give them access. But if you really want to know what I think, and I'm usually willing to tell people what I think, I think the proof of concept is there. I think we know that in the setting of highly effective and very tolerable adjuvant targeted treatment in the EGFR space with osimertinib, in the ALK space with alectinib, if anything, drugs like selpercatinib and pralsetinib in RET fusion positive lung cancer in the advanced setting are just as well tolerated and easily as effective and long lasting. And so, I think if you did a trial and they are doing trials looking at these drugs in the adjuvant space, almost certainly you're going to see the same really dramatic disease-free survival benefit from these treatments, which, at least in the EGFR space, seems to have translated into an improvement in overall survival. And so if I had a stage II or a resected stage 3, especially a RET fusion positive patient today, I would definitely talk to them about off-label use of a RET inhibitor if I could not find a trial. Now, I understand that there are going to be reimbursement issues and whatnot associated with that, but I think the extrapolation is worth discussing. Dr. Vamsi Velcheti: Yeah, I think it's really challenging because some of these fusions are so rare and it's hard to really do large adjuvant trials for some of these rarer subgroups. Nate, fascinating insights. Our listeners will find links to the abstracts we discussed today in the transcript of the episode. And Nate, I look forward to catching up with you at the Annual Meeting, and again after the meeting for our wrap up podcast to discuss the practice-changing lung cancer abstracts and highlights from the Plenary Session. Thank you so much for joining us and sharing your insights today. Dr. Nathan Pennell: Thanks for inviting me. Vamsi. I look forward to touching base after we get to see all the late-breaking abstracts. Like I said, this is, I think, a year for lung cancer with a lot of exciting data, and I know we'll have a lot to talk about. Dr. Vamsi Velcheti And thank you so much to all our listeners for your time. If you value the insights that you hear from the ASCO Daily News Podcast, please take a moment to rate and review and subscribe wherever you get your podcast.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Find out more about today's speakers: Dr. Vamsi Velcheti @VamsiVelcheti   Dr. Nathan Pennell @n8pennell   Follow ASCO on social media:   @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn     Disclosures: Dr. Vamsi Velcheti: Honoraria: ITeos Therapeutics Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen, Elevation Oncology, Taiho Oncology, Merus Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline   Dr. Nathan Pennell:   Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron  Research Funding (Inst): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi 

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How do you live as a Christian in a Post-Christian culture? Friday on Mornings with Eric and Brigitte, Tim Sansbury, Professor of Philosophy and Theology at Knox Theological Seminary joins us to talk about the Kingdom Come event March 14-17 at Coral Ridge Presbyterian Church and his Plenary Session topic, A Life Well Led; Demonstrating the Faith in a Post-Christian Society. Kingdom Come Conference - Coral Ridge Pres. Church - March 14-17See omnystudio.com/listener for privacy information.

Think about the phrase "New Age". What comes to mind? Old documentaries and images of hippies at Woodstock? Thursday on Mornings with Eric and Brigitte, author, speaker, and worship leader, Alisa Childers tells us that many Christians aren't even aware of how New Age beliefs have infiltrated Christianity through the Progressive Church, and she will discuss this topic at the CRPC Kingdom Come Conference March 14-17. Don't miss her Plenary Session at 7:30 p.m. on Thursday, March 14, "Spiritual But Not Religious: How New Age Beliefs Are Infiltrating The Church". Kingdom Come Conference - Coral Ridge Pres. Church - March 14-17See omnystudio.com/listener for privacy information.

Two of the highest profile presentations at the recent ASCO GU Meeting were the plenary presentations of the CONTACT 02 trial, and the Keynote-564 trial. Generally speaking, these were well received; indeed quite enthusiastically received in some quarters! Not however in the quarter of prolific oncology commentator and Haematologist/Oncologist & Professor of Epidemiology,  Dr Vinay Prasad! “Unethical” and “sh**ty” are just some of the terms he used to describe these in two episodes of his podcast, “Plenary Session”. Declan and Renu take Vinay to task for some of the somewhat personal attacks he makes on colleagues, but do enjoy listening to his critique, and indeed agree with many of his points!  Even better on our YouTube channelLinks:Plenary Session podcast on Contact 02 Plenary Session podcast on Keynote-564 Dr Vinay Prasad Twitter 

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Jubala CoffeeNational Advisory Committee on Microbiological Criteria for Foods (NACMCF) | Food Safety and Inspection ServiceWhat is a Plenary Session?Parameters for determining inoculated pack/challenge study protocols - PubMed13th Microbial Challenge Testing for Foods Workshop - International Association for Food ProtectionPast Presidents - International Association for Food ProtectionBuffalo Trace Bourbon - HomeAdam Johnson (ice hockey) - WikipediaSkate Blade Neck Lacerations: A Survey and Case Follow-up : Clinical Journal of Sport MedicineInfluence of Neck Laceration Protectors on Cervical Range of Moti…: Ingenta ConnectUSA Hockey Board of Directors unanimously voted…Which FoodCORE/FoodNet Pathogen Are You?Tyson Recalling Dinosaur Chicken Nuggets After Complaints of Metal Pieces - The New York TimesTyson recalls nearly 30,000 pounds of dino chicken nuggets - CBS NewsFood Safety & Quality Assurance Manager - TikTokNicole Potenza | LinkedInHow to Plan Thanksgiving Dinner - The New York TimesThe Biggest Thanksgiving Turkey Mistakes, According To Food Safety Experts | HuffPost Life86. Thawing Poultry at Room Temperature — Risky or Not?Don Schaffner

Eleventh Annual Executive Branch Review Conference — EBRXITheme: Transparency, Accountability, and the Administrative StateThe White House recently released much-anticipated changes to federal regulatory practices, including a new Executive Order 14094 on “Modernize Regulatory Review,” draft revisions to Circular A-4 governing regulatory impact analysis, and draft guidance on meetings with entities outside of the executive branch. The Office of Information and Regulatory Affairs (OIRA) has the lead for implementing these changes, which comprise the most significant regulatory policy initiatives of the Biden administration. In this opening session, OIRA experts, including several former OIRA administrators will review these developments.Featuring:Anthony Philip Campau, Principal, Clark Hill Public Strategies & Attorney, Clark Hill PLCSusan Dudley, Director, GW Regulatory Studies Center & Distinguished Professor of Practice Trachtenberg School of Public Policy & Public Administration, George Washington UniversitySally Katzen, Professor of Practice and Distinguished Scholar in Residence & Co-Director of the Legislative and Regulatory Process Clinic, New York UniversityModerator: Andrew Olmem, Partner, Mayer Brown

Earlier this month, the White House released much-anticipated changes to federal regulatory practices, including a new Executive Order 14094 on “Modernize Regulatory Review,” draft revisions to Circular A-4 governing regulatory impact analysis, and draft guidance on meetings with entities outside of the executive branch. The Office of Information and Regulatory Affairs (OIRA) has the lead for implementing these changes, which comprise the most significant regulatory policy initiatives of the Biden administration. In this opening session, OIRA experts, including several former OIRA administrators will review these developments.

Drs. Shaalan Beg and Shiraj Sen discuss notable advances in GI cancers featured at the 2023 ASCO Annual Meeting, including the PROSPECT and PRODIGE-23 trials in rectal adenocarcinoma, the MORPHEUS study in uHCC, and the NORPACT-1 trial in pancreatic head cancer. TRANSCRIPT     Dr. Shaalan Beg: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Shaalan Beg, your guest host for the podcast today. I'm the vice president of oncology at Science 37, and I'm an adjunct associate professor at UT Southwestern Medical Center. My guest today is Dr. Shiraj Sen. He is a GI medical oncologist and the director for clinical research at NEXT Oncology in Dallas.   Today, we'll be discussing practice-changing studies and other key advances in GI cancers that were featured at the 2023 ASCO Annual Meeting.   You'll find our full disclosures in the transcript of this episode, and disclosures of all guests on the podcast are available on our transcripts at asco.org/DNpod.   Shiraj, it's great to have you on the podcast today.  Dr. Shiraj Sen: Thanks so much for having me today, Shaalan.  Dr. Shaalan Beg: We saw exciting new data and great progress in GI oncology at the ASCO Annual Meeting. I was hoping we could talk about LBA2. This was the PROSPECT study that was presented during the Plenary Session. It's a randomized, phase 3 trial of neoadjuvant chemoradiation versus neoadjuvant FOLFOX chemo, followed by the selective use of chemoradiation, followed by TME or total mesorectal excision for the treatment of locally advanced rectal cancer. This is the Alliance N1048 trial. What are your thoughts on this study?  Dr. Shiraj Sen: Thanks, Shaalan. It was great to see another GI study presented in a Plenary Session, and I thought this was a great trial that really took us back to thinking about why we do chemoradiation as well as chemotherapy perioperatively in locally advanced rectal cancer. And asking the important question of is there a select patient set or subset where we might be able to safely omit the chemoradiation piece.  To me, the impressive part was this study enrolled from 2012 to 2018. In 2012, when this treatment really started enrolling, the standard of care was long-course chemoradiation for five and a half weeks, followed by surgery, followed by adjuvant chemotherapy with FOLFOX or CAPOX. During this time, a lot of the practices of these patients have shifted from that to giving total neoadjuvant therapy, where we bunch the chemotherapy and chemotherapy upfront prior to the patient undergoing surgery. And this study really asked us to take a look at both practices and ask the question of which one is better and is it possible to de-escalate care for patients who get upfront chemotherapy and omit the chemoradiation and still have similar outcomes.   I thought it was very interesting that this was done in a non-inferiority-type manner, and we can talk more about that in a few minutes as well. But taking that all into context, the fact that in this study, that the non-inferiority endpoints were met for both disease-free survival as well as overall survival in the patients who were able to omit chemoradiation, I think in the big picture sense told us that there truly might be a patient subset where—this is in patients with T2 node-negative disease or T3 node-negative or T3 node-positive disease—where we might be able to safely exclude the chemoradiation and still have similarly effective outcomes for these patients.  Dr. Shaalan Beg: Those are great points, especially when we have started to think about colon cancer and rectal cancer as many different diseases based on their location. And we know that in some instances their biology can be different as well.   Can you talk a little bit about who those patients are that were enrolled on this trial? Because when I think about the German rectal study that led to us using neoadjuvant chemoradiation, the data was really around pelvic control of disease and sphincter preservation. So how did the patients who enrolled in this trial relate to the typical person with rectal cancer who walks through your doors?   Dr. Shiraj Sen: Yeah, great point. I think we should point out the inclusion-exclusion criteria for this study. These patients were only those who were, again, T2 node-positive or T3 node-positive or negative, patients for whom chemoradiation would be indicated in the setting, and patients for whom they'd be good candidates for sphincter-sparing surgeries. So, tumors that are quite up high. These are not for individuals who have tumors requiring an APR. These are not for patients who have clinical T4 tumors. And this is not applied, again, to those high-risk patients who have 4 or more pelvic lymph nodes that are 1 cm in size or larger in the short access. And so, patients who need essentially an APR and the high-risk T4 tumors who are, I think, better suited by something like we'll talk about later in the PRODIGE study.   I think one last point that might be worth making here on the PROSPECT trial is that it was a non-inferiority trial. And in my opinion, this was really a great use of a non-inferiority study. I believe that when there's a new treatment under consideration used in a non-inferiority study, it should be because that therapy or modality of treatment is safer, more cost-effective, or could help increase access to care without compromising efficacy, and ideally maybe more than one of the above. And in this case, I think really all of those checkboxes are met.   In urban settings where we work, we think about access to radiation being quite plentiful, but when we get to more rural areas, or parts of the world where they may not have access to radiation like we may, I think this data can help drive care for a number of patients there. It can certainly be more cost-effective as it allows the omission of radiation. And certainly, from some of the PRO data that they presented, it certainly can be felt to be safer and help omit some toxicities as well.  Dr. Shaalan Beg: Yeah, you mentioned a total neoadjuvant therapy and we seem to be entering this space in rectal cancer where the decision on which modalities an individual person will need for the management of their disease and what sequence they will need is all up for debate, whether that's chemotherapy or radiation, long-form, short-form radiation. And we also heard some results at earlier ASCO meetings around the omission of surgery in people who've had complete clinical responses as well.   And you mentioned total neoadjuvant therapy and at ASCO this year we heard the results from LBA3504, which is a PRODIGE-23 trial. The investigators reported 7-year results of this phase 3 study from the UNICANCER group in France. This study is really pushing the envelope. What are your key takeaways here?   Dr. Shiraj Sen: Great point. I think this study, especially when taken in conjunction with the PROSPECT trial, highlights the fact that these patients really can have heterogeneous diseases and ones that really require careful consideration and discussion at multidisciplinary tumor boards. Unlike the patient population in the PROSPECT trial, the PRODIGE study did treat patients with higher-risk disease. So these were patients with clinical T3, T4 tumors and so higher risk, and asked the question now with more mature 7-year follow-up of, when compared to receiving the standard of care at the time, which was a chemoradiation followed by TME, followed by adjuvant FOLFOX for 12 cycles or the capecitabine, does TNT giving again now modified full FOLFIRINOX for six cycles followed by chemoradiation followed by TME and then adjuvant FOLFOX, do the improvements in both disease-free survival, overall survival, and metastatic relapse rate, do they hold up, and/or are there any differences in local control?   And again, here they demonstrate that even with longer-term follow-up, that the improvements in OFS, DFS, and metastatic relapse rate, really do hold up even with longer-term follow-up. And so, for these patients with higher risk disease, it does seem that giving induction chemotherapy with modified FOLFIRINOX before chemoradiotherapy really might be kind of best practices. The safety profile, even with longer-term follow-up was unchanged. There was not any increase in local recurrences. And again, looking at quality of life metrics there seemed to be similar or maybe improved quality of life for patients who receive the TNT approach. And now again, I think the next step is, as the presenter mentioned, investigating this even in a more tailored fashion, as was done with the PROSPECT study.  Dr. Shaalan Beg: Let's change gears and talk about liver cancer. Abstract 4010 showed the results of the MORPHEUS-liver study. This was a phase 1b/2 randomized trial of tiragolumab in combination with atezolizumab and bevacizumab for people with unresectable locally advanced or metastatic hepatocellular cancer. It's really exciting to see innovations with immune therapy changing how we've managed hepatocellular cancer in the last few years. And here, we're seeing an addition of a third agent to an already approved regimen of atezolizumab and bevacizumab. I was really curious to hear what your take-home message is from this study.   Dr. Shiraj Sen: Yeah, this was another very interesting abstract that was presented at ASCO this year. It's hard to believe that it was only 3 years ago that we first got the approval of atezo plus bev, and that it took more than a decade to really have us as a field improve on outcomes for patients with liver cancer above and beyond giving sorafenib. And here we are just 3 years later, already launching new phase 3 studies from these sorts of early-phase adaptive signal-seeking studies. The investigators as a whole should be commended for the speed at which new drug development has really progressed in liver cancers after, again, quite a lull we had in the pre-I/O days.   It's encouraging to see that in just 3 years that there's another phase 3 study now being launched in HCC on the heels of this data combining the atezo-bev backbone to the anti-TIGIT molecule tiragolumab. Now, I know there was a lot of discussion and some criticism of this study and what the real effects of adding tiragolumab to atezo-bev might be because of the underperformance of the control arm. In this study, the atezo-bev control arm, it should be noted that was only 18 patients, had a response rate of only 11%. And of course, with longer-term follow-up of the IMbrave150 study, we know that with the atezo-bev, we expect a response rate of about 30%. And so how a real-world population of individuals receiving atezo-bev would compare to those receiving tiro-atezo-bev has been discussed. But I think the only real way to answer that question would be with a large, randomized phase III study. And it's encouraging to see that one is being launched to ask that question.    Dr. Shaalan Beg: Absolutely. Let's change gears and talk about pancreatic cancer. LBA4005 explored short-course neoadjuvant FOLFIRINOX versus upfront surgery for people with resectable pancreatic head adenocarcinoma in the NORPACT-1 study. This is a multicenter randomized phase 2 trial and we're starting to see the reporting of clinical trials evaluating the sequencing of systemic therapies for resectable disease. We've heard studies for neoadjuvant therapy for borderline resectable as well as resectable trials in previous meetings. But there's a lot of discussion around the NORPACT-1 trial which may be causing some people to pause on our current understanding of treatment sequencing for resectable disease. I'm curious to hear what your take homes are.   Dr. Shiraj Sen: Thanks. Yes, I thought this was a very interesting study as well. Depending on which institution one practices in, in recent years, many have shifted their practice for individuals with resectable pancreatic cancer from administering full FOLFIRINOX or adjuvant therapy only after surgery to giving it in the neoadjuvant setting based on, again, a number of smaller studies, some that are single institution. This is one of the first studies that in a randomized fashion has asked the question in just resectable pancreatic cancer. So we're not talking about borderline resectable or other patients.    But in resectable pancreatic cancer, whether there are differences now comes if patients receive surgery first, followed by FOLFIRINOX-only adjuvant setting or essentially getting perioperative FOLFIRINOX and so neoadjuvant, followed by surgery, followed by, as tolerated, four cycles of adjuvant FOLFIRINOX. And I was a little surprised by some of the results and to me some of these data were a little intriguing.  Specifically, I think if we take a deeper look like the discussant had after the presentation, there are, I think, some unanswered questions. Specifically, half the patients were randomized to receive neoadjuvant FOLFIRINOX and half of them received upfront surgery. But in the group of individuals who received neoadjuvant FOLFIRINOX, it looked like only half of them completed neoadjuvant chemotherapy. And some answers into kind of why that was, and what it was about those patients then who were in the neoadjuvant arm, is one thing that comes to mind.    Secondly, what I thought was interesting was this study was that it was designed very well to try to take out as much heterogeneity as possible. However, in both arms, there was actually quite a substantial number of individuals who ended up receiving gemcitabine-based chemotherapy. And that's even in the patients who received neoadjuvant FOLFIRINOX, and individuals who received neoadjuvant FOLFIRINOX, only 25% post-op went on to receive adjuvant FOLFIRINOX. And 75% almost received gemcitabine-based therapy. And again, why so many patients received off-protocol adjuvant therapy is something that kind of struck me.  I think the third and final thing that really struck me was, in the patients that received neoadjuvant FOLFIRINOX, there was a higher rate of R0 resections. 56% of patients had an R0 resection compared to those who got upfront surgery, where there was only a 39% rate and similarly kind of higher levels of N0 resection. And yet, despite all of this, again, the authors did show quite clearly that there were not any significant improvements in outcomes for patients that received neoadjuvant therapy, but kind of how improved surgical endpoints do not translate to overall survival and overall endpoints; I think there are still some questions there.    However, I do agree overall that despite these limitations with the conclusions of the author, that at this time at least, it's not clear; the results don't support the widespread use of neoadjuvant FOLFIRINOX as a standard of care for resectable pancreatic cancer. Fortunately, there are studies ongoing, like the Alliance [for Clinical Trials in Oncology] study and the PREOPANC-3 study that hopefully will kind of help settle this verdict.    Dr. Shaalan Beg: Yeah, it's a stark reminder that we need better treatments. I think we've been shifting the sequencing of these treatments and slicing them in as many ways as we can. And the core challenge is in finding better systemic therapies that have been found to be effective in advanced stage as well as in curative stages like this. And one of the points that bothered me about this trial was the drop-off that they saw at the beginning when the biliary system was being drained, or they were getting biopsies because folks who went for surgery upfront didn't always require those procedures. They didn't require histologic diagnosis either. But as is standard practice, before we give systemic therapy, we require psychologic confirmation. And that may have introduced a delay of a couple of days or a couple of weeks, which could have resulted in some imbalances in how survival is measured and how folks were doing. Because, as you know, a lot of times people diagnosed with this disease can be fairly sick, and a matter of a couple of days or weeks can make a big difference in terms of treatment with those.  I'm really excited to wait and hear how the Alliance study and the PREOPANC follow-up trials pan out and as a very important cautionary note for everyone, both the folks who have adopted neoadjuvant therapy and those that have not followed the data. And kudos to the investigators for completing that trial.  Dr. Shiraj Sen: Yeah, I fully agree. I'm glad to see that these trials are being run. I think we should not take anything away from the fact that these are very challenging trials to run. I think we certainly owe a big kudos to the patients who enroll in these studies who have resectable disease, but they're still willing to go through the process of an extra consent form, an extra kind of screening process, additional testing required to go into a clinical trial. And it's only because of them that we're able to run these studies and, as a field, get some answers on how to best take care of our patients.   Dr. Shaalan Beg: Shiraj, thank you so much for coming to the podcast today and sharing your valuable insights on the ASCO Daily News Podcast.   Dr. Shiraj Sen: Thank you so much for having me, and to all of the ASCO staff for having this podcast.  Dr. Shaalan Beg: And thank you to our listeners for your time today. You'll find links to the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the podcast, please take a moment to rate, review and subscribe wherever you get your podcasts.    Disclaimer:   The purpose of this podcast is to educate and inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.    Find out more about today's speakers:   Dr. Shaalan Beg  @ShaalanBeg  Dr. Shiraj Sen  @ShirajSenMDPhD     Follow ASCO on social media:   @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn     Disclosures:    Dr. Shaalan Beg:   Consulting or Advisory Role:  Ispen, Cancer Commons, Foundation Medicine, Genmab/Seagen   Speakers' Bureau: Sirtex   Research Funding (An Immediate Family Member): ImmuneSensor Therapeutics   Research Funding (Institution): Bristol-Myers Squibb, Tolero Pharmaceuticals, Delfi Diagnostics, Merck, Merck Serono, AstraZeneca/MedImmune     Dr. Shiraj Sen:   Employment: Roche/Genentech  Stock and Other Ownership Interests: Roche/Genentech  Research Funding (Institution): ABM Therapeutics, Zentalis Pharmaceuticals, Parthenon Therapeutics, Pyxis Oncology, Georgiamune Inc.      

Drs. John Sweetenham and Marc Braunstein discuss advances in hematologic malignancies featured at the 2023 ASCO Annual Meeting, including the potentially practice-changing SWOG-S1826 study in Hodgkin lymphoma, the promise of bispecific antibodies in B-cell malignancies, and a novel approach to deliver vital anti-myeloma medications that could improve patient quality of life and alleviate barriers to care. TRANSCRIPT   Dr. John Sweetenham: Hello, I'm John Sweetenham, the associate director for cancer network clinical affairs at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center and the host of the ASCO Daily News Podcast.    The 2023 ASCO Annual Meeting featured some exciting new data on hematologic malignancies. I'm delighted to have Dr. Marc Braunstein return to the podcast to discuss some of these potentially practice-changing studies and new approaches in the heme space. Dr. Braunstein is a hematologist and oncologist at the NYU Perlmutter Cancer Center.    You'll find our full disclosures in the transcript of this episode, and disclosures of all guests on the ASCO Daily News Podcast are available on our transcripts at asco.org/DNpod.   Marc, it's great to have you back on the podcast, and thanks for being here again.   Dr. Marc Braunstein: Thank you, John. It's great to be back.   Dr. John Sweetenham: Marc, we already mentioned that there are some potentially practice-changing studies that were reported at ASCO this year. And among those, LBA4, which was presented in the Plenary Session, was a study which explored the treatment of advanced Hodgkin lymphoma. This was the Southwest Oncology Group study S1826. Could you give us your insights on this?    Dr. Marc Braunstein: Sure, happy to discuss S1826. So as background, you know, the ECHELON-1 study, which was published in the New England Journal of Medicine in 2022 showed a 40% decrease in the risk of death at six years follow-up by adding brentuximab to AVD compared to bleomycin AVD. And that was in high risk or advanced-stage patients and that led to adoption of brentuximab for upfront use in patients with classical Hodgkin lymphoma in advanced stage.    Also of note, immune checkpoint inhibitors such as pembrolizumab or nivolumab do have activity in the relapse setting. The SWOG S1826 study was a randomized control study looking at the use of the PD-1 inhibitor nivolumab plus AVD versus brentuximab AVD in patients with advanced stage classical Hodgkin lymphoma who are at least twelve years of age. And the primary endpoint in the study was progression-free survival.     It was a large study which enrolled 976 patients and randomized them one to one to either nivo AVD or brentuximab AVD. The median age in the study was 27 and the median follow-up was 12 months. And what the study found, which could be practice-changing, was that the primary endpoint of progression-free survival was superior in the nivolumab arm with a hazard ratio of 0.8 and a one-year PFS of 94% versus 86%, favoring the nivolumab arm. And while there were side effects associated with the class of medications, for example, hypo or hyperthyroidism was more frequent in the nivolumab group, whereas peripheral neuropathy was higher in the brentuximab group, I think that these results are particularly encouraging for how we can continue to improve outcomes for patients with advanced-stage classical Hodgkin lymphoma. And this may be practice-changing in terms of whether we use upfront immune checkpoint inhibitors in combination with our standard chemotherapy backbone.    Dr. John Sweetenham: Yeah, absolutely. There are a couple of things that occur to me. One in particular which is unique about this study, and the fact that it was for patients who are 12 years and older in many respects represents a first because I can't think of another large, randomized study of this type which has attempted to align pediatric and adult care of patients with Hodgkin lymphoma. So, I think it's something of a landmark in that regard. I don't know if you'd agree with that.    Dr. Marc Braunstein: I agree, especially with the range of ages from 12 to 83. It's a pretty broad population by age, but I agree it does kind of reconcile those two groups in a disease that has a bimodal presentation and clearly shows that immune checkpoint inhibitors are both potent and well tolerated in different age groups.    Dr. John Sweetenham: The other question that I have about this study is we haven't seen so far in this study an overall survival benefit to the nivo arm, which is maybe not surprising, but in terms of the practice-changing potential of this study, do you think that will matter?   Dr. Marc Braunstein:  I think that's an excellent question, John. Initially, the ECHELON-1 study only showed progression-free survival, and then the update did show overall survival. And so if we take the lead from that study, we expect to see an overall survival benefit in the SWOG study as well with nivolumab, but it remains to be seen. But I think that the data presented thus far at the Plenary Session is compelling enough to consider using nivolumab upfront.   Dr. John Sweetenham: Yeah, I absolutely agree. And then I guess the other question that we're going to have to wait probably several years to know is what happens in terms of relapse? So, for the minority of these patients who do relapse, how salvageable, if that's the right word, are they going to be with a second- or third-line regimen? But I think that's clearly something for the future, and it's a very interesting, exciting outcome from this study.   Dr. Marc Braunstein: Absolutely.    Dr. John Sweetenham: Let's move on. Marc, again, we're still in the lymphoma world here, but looking at high-risk follicular lymphoma. And this was Abstract 7506, looking at epcoritamab plus the R2 regimen in patients with follicular lymphoma. Could you walk us through this one?    Dr. Marc Braunstein: Yeah, absolutely. Bispecific T-cell engaging antibodies are showing impressive efficacy in relapsed and refractory non-Hodgkin lymphoma. Epcoritamab is a bispecific antibody that binds to CD3 on T-cells and CD20 B-cells. And this antibody is currently approved for diffuse large B-cell lymphoma patients after two or more prior lines of treatment.    In this study presented by Merryman and colleagues, they explored the addition of epcoritamab to standard lenalidomide-rituximab. In 109 patients with relapsed or refractory follicular lymphoma who had at least one prior therapy, and, of note, the study was enriched for high-risk patients for progression, including those who had progression of disease within 24 months of their initial treatment and those patients who had been refractory to prior anti-CD20 treatment. This study enrolled 109 patients with relapsed refractory follicular lymphoma. The median age was 65 and 56% of patients had FLIPI scores on the higher end of the spectrum from three to five, and 61% had stage 4 disease. Also of note, 38% of patients had progression of disease within 24 months of their prior treatment. So at a median follow-up of 8.8 months, the overall response rate was impressive at 97%, and 82% of patients were still on treatment at that time.     Now, of course, with this mechanism of action of bispecific antibodies, there is a risk of both cytokine release syndrome and immune-related neurotoxicity. The rates of CRS were primarily low grade, there were only 2% grade 3, and of note, most occurred after the first dose. And in terms of ICANS or neurological toxicity, there were no grade 3 adverse events, and those occurred in only two patients. Finally, the estimated six months progression-free survival was 93%. So, if we cross-compare these results historically to the R-squared regimen, which was published to be about 80%, just cross comparing, so it's not exactly the same study, this clearly shows high activity on par or better with R-squared alone. Although this study was not a randomized study, I think the addition of epcoritamab certainly shows high overall response rates and we'll need randomized data to confirm the efficacy, but it's definitely encouraging in high-risk follicular lymphoma patients.   Dr. John Sweetenham: Thanks, Marc. I agree. I think these data are really enticing, in as much as the response rates are so high, but of course, it is follicular lymphoma, so we'll have to wait a while. But the thing that it does make me reflect on is that bispecific antibodies really are turning out to be remarkably effective in a range of B cell malignancies, so, it's very interesting to continue to watch this space.    I'm going to change gears now and talk about something completely different for a moment. And this was Abstract 1536. I think that many of us are in a position where we're now looking at how we deliver our clinical services, and particularly inpatient services, to patients with hematologic malignancy. And this study addressed that very specifically. Can I have your thoughts on that?   Dr. Marc Braunstein: Sure. In the context of how our therapies are improving, our approaches to how we manage patients clinically is changing too, in many ways for the better. So, various models exist for, you know, which practitioners manage oncology patients who happen to be admitted to the hospital. This abstract, which was performed by authors at a large medical center in New York, describes the use of a dedicated hematologic malignancy hospitalist for managing medicine-related issues. And the authors did comparisons of that service to a service primarily managed by oncologists. The authors compared things such as length of stay, whether the patients were discharged by noon, which is a hospital metric that's used for facilitating turnover of patients and space availability, as well as 30-day readmission rates among patients cared for by an oncology attending versus this heme malignancy hospitalist between July of 2021 and July 2022.    The outcomes showed that admissions to the heme malignancy hospitalists were, although less because that service was primarily for patients who required medicine-related issues as opposed to primarily oncologic issues, there were 95 admissions to that service versus 669 to the oncology service. There was a significantly shorter length of stay on the heme malignancies hospitalist service by about 2 to 5 days compared to the oncology hospitalist service. The rates of patients who were discharged by noon or the length of stay were similar between the two groups.    So, while this study is confounded by differences in acuity of disease between the services, using a dedicated heme malignancy hospitalist has many benefits, not just to offload the oncology-managed service, which may have a higher level of acuity, but also allow for a deviation of care for medicine-specific issues, to a hospitalist that's specifically trained in managing patients with hematologic malignancies and then dedicating the oncology specialty service to those who need acute oncologic care, such as those with leukemia or other high acuity diseases.    Dr. John Sweetenham: Thanks, Marc. I think it is really interesting to see some outcome data for this model of care. A number of centers I know are looking at an APP-led inpatient service for these types of patients, too, so it's going to be very interesting to see how further studies of these kinds of approaches continue to develop.    And on a related theme of changes in patterns of care, Abstract TPS1609 looked at home infusion and of course, this is something that really started to attract a lot more attention during the COVID-19 pandemic. But I wonder if you could walk us through some of the details of this poster.    Dr. Marc Braunstein: This study was presented as a poster proposing a prospective study looking at home infusion of the anti-CD38 monoclonal antibody daratumumab, which has a vital role in managing patients with newly diagnosed or relapsed multiple myeloma. And monoclonal antibodies have really revolutionized the care of patients with multiple myeloma, but often their infusion schedule is weekly or biweekly, and it does require relatively frequent visits to an infusion center.    So, this single-arm, open-label study is going to examine whether we can provide home administration of subcutaneous daratumumab and assess whether it improves quality of life and assess its safety. So, in this study, a visiting nurse will come and deliver the medication after patients take their pre-medications at home prior to the arrival of the infusion nurse. And then the investigators will provide quality of life questionnaires prior to and after the infusions and at the end of the study, and they'll be looking at any barriers to adherence, any barriers to the logistics of this home infusion arrangement.    And I think that this has a lot of potential not just to improve quality of life, but also to facilitate care to patients who may be frail, who may not have good caregiver support, who may have barriers in traveling to an infusion center or perhaps in places that are more resource-deprived and don't have local infusion centers. This could be a potential approach to delivering vital anti-myeloma medications at home, and I'm looking forward to seeing the results.    Dr. John Sweetenham: Yeah, I agree. I think a lot of us still have anxieties about the safety of this approach, but I think there are increasing data to suggest that home infusion is not only safe but also, as you mentioned, is a big enhancer of the quality of life of these patients. And so, very interesting to see how this plays out in prospective studies.    So, to close out, I wonder if you could walk us through Abstract 7072, a poster looking at the issue of clonal hematopoiesis.    Dr. Marc Braunstein: Clonal hematopoiesis, which is a phenomenon in which the blood cells acquire somatic mutation, is associated with both cardiovascular disease adverse outcomes as well as hematologic malignancy. It's been shown to be a precursor for diseases such as leukemia. So, this relatively small study from MD Anderson Cancer Center examined clonal hematopoiesis in 78 patients with malignancies, 70% of which had a history of cancer, and the authors described outcomes associated with clonal hematopoiesis.    So, again, 78 patients were examined, and 76% of them had a history of malignancy, and 73% had other comorbidities. And the authors demonstrated clonal hematopoiesis by the finding of specific mutations in the blood associated with clonal hematopoiesis. The authors essentially looked at outcomes such as mortality. They noted that only 20% of the patients developed a myeloid neoplasm, and that's relevant because, again, clonal hematopoiesis is a precursor for myeloid neoplasms. They also noted that most patients had died from a primary malignancy rather than a myeloid neoplasm, which is not too surprising considering that most patients with clonal hematopoiesis will not develop a hematologic malignancy, but it is a marker for the potential transformation.    And so, I think the authors conclude that clonal hematopoiesis is important for monitoring patients who are at risk for potential myeloid transformation and hematologic malignancy, but it's not necessarily the case that patients who have a background of malignancy will often develop a myeloid malignancy. I think there are many implications of clonal hematopoiesis for cancer in general in terms of the risk of secondary malignancies in those treated with adjuvant chemotherapy, in terms of how we monitor patients who actually more and more are going to have this detected as we use more next-generation sequencing and liquid biopsies.     So, I look forward to future studies that are exploring how to actually prospectively assess clonal hematopoiesis and use it for clinical stratification for things like adjuvant chemotherapy or monitoring for risks of hematologic malignancy.    Dr. John Sweetenham: Thanks, Marc. I agree. Very important for the future, especially as we gain more and more sequencing data.    So, Marc, in conclusion, I want to thank you very much for sharing your insights with us today on the ASCO Daily News Podcast. It's been great to talk with you again.    Dr. Marc Braunstein: My pleasure. Happy to be back, and I look forward to a future podcast session.  Dr. John Sweetenham: And thank you to our listeners for joining us today. You'll find links to the abstracts discussed today in the transcripts of this episode. Finally, if you value the insights that you hear on ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclaimer:   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.    Find out more about today's speakers:   Dr. John Sweetenham   Dr. Marc Braunstein   @docbraunstein      Follow ASCO on social media:    @ASCO on Twitter    ASCO on Facebook    ASCO on LinkedIn       Disclosures:   Dr. John Sweetenham:   Consulting or Advisory Role: EMA Wellness   Dr. Marc Braunstein:   Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb/Celgene, Adaptive Biotechnologies, GlaxoSmithKline, ADC Therapeutics, Janssen Oncology, Abbvie, Guidepoint Global, Epizyme, Sanofi, CTI BioPharma Corp   Speakers' Bureau: Janssen Oncology   Research Funding (Institution): Janssen, Celgene/BMS        

Drs. Vamsi Velcheti and Jack West discuss ADAURA, KEYNOTE-671, and KEYNOTE-789 trials in NSCLC and the first pivotal study of sunvozertinib for the treatment of NSCLC with EGFR exon 20 insertion mutations. TRANSCRIPT Dr. Vamsi Velcheti: Hello, I'm Dr. Vamsi Velcheti, your guest host for the ASCO Daily News Podcast. I'm a professor of medicine and director of thoracic medical oncology at the Perlmutter Cancer Center at NYU Langone Health. My guest today is Dr. Jack West, a thoracic oncologist and associate professor in medical oncology at City of Hope Comprehensive Cancer Center. Today, we'll be discussing practice-changing studies and other key advances in lung cancer that were featured at the 2023 ASCO Annual Meeting.   Our full disclosures are available in the transcript of this episode and disclosures of all guests on the ASCO Daily News podcast are available at asco.org/DNpod.   Jack, there was a lot of exciting new data that emerged from the ASCO Annual Meeting, and it's great to have you back on our podcast today to talk about all the key updates in lung cancer.   Dr. Jack West: Absolutely. Thanks so much. It's always a high-energy meeting, and there was a lot to talk about in the lung cancer sessions this year for sure.  Dr. Vamsi Velcheti: Let's begin with LBA3, the ADAURA trial. This was presented in the Plenary Session at ASCO; we've heard previously the DFS updates from previous meetings, and overall survival updates were presented at the ASCO 2023 Annual Meeting. So, Jack, what was the highlight of the presentation for you? And could you put things in context for us? We have known about the DFS data for a while now. What gets you so excited about this study?  Dr. Jack West: Well, we've actually been focused on this trial for literally 3 years, since Dr. Herbst presented it at another Plenary presentation back in the ASCO Meeting in 2020 when we saw tremendous differences in the DFS data. Again, this was a trial of patients with resected stage 1b to 3a EGFR mutation-positive non-small cell lung cancer. Nearly 700 patients were randomized to after-surgery, and for many, but not all, patients undergoing chemotherapy, it wasn't mandated. But after that, they were randomized to get adjuvant, placebo, or osimertinib for up to 3 years. And we saw huge differences in the disease-free survival from the first presentation, with a hazard ratio in the range of 0.2.   We have notably seen significant improvements in disease-free survival before with other EGFR TKIs for this population after surgery, but nothing in this range. And it's also notable that in the various other trials of other EGFR inhibitors in the postoperative setting, we've seen a DFS benefit, but that didn't translate to an improvement in overall survival. So, seeing a press release that this was associated with a significant and, in fact, highly significant by report, improvement in overall survival, as well as DFS, was really notable.   What's also, I think, particularly important as a focus of this is that in the later presentations of this work, with longer follow-up last year, we saw that the DFS curves showed a drop in the DFS starting after these patients had completed 3 years of treatment. So, really suggesting that at least some, if not many or most of these patients who had been on adjuvant osimertinib were subject to a higher risk of relapse once they completed that. So, again, making the endpoint of overall survival particularly important. It's always been to me the endpoint we should care about most in a curative setting. Although the DFS was the primary endpoint of the study and it was powered and built around specifically focusing on the DFS difference, so overall survival was reassuring, I think, when we actually saw it, but not what the trial was centered around.    And what we saw was a very dramatic improvement in overall survival with a hazard ratio of 0.49. That was essentially the same for the patients with stage 2 to 3a disease, as well as the broader population with stage 1b to 3a disease. When we look at the absolute numbers for overall survival at 5 years, there was an improvement from 73% to 85% with osimertinib, and in the population from 1b to 3a, an improvement from 78% to 88%. So, many things to comment on here. Really remarkable to see an 88% 5-year survival in the osimertinib arm that includes patients with stage 3a disease.    I would say that there's still some controversy, some questions about this, and it really centers around a few things. One is, like many global trials, this one enrolled patients from many places that did not have the same standard of care staging that we follow in the U.S. There wasn't any specification or mandate for PET scans, which would be very routine in the U.S. And brain MRIs were not mandated either. And so there were almost certainly some patients with more advanced disease that was not detected that would be a big advantage for the osimertinib arm, but really not characterized. And also, the crossover was made possible to osimertinib starting in April of 2020, but only 38.5% of the patients on the control arm actually received osimertinib at the time of relapse. And even though many of the other patients who had a relapse did get another EGFR inhibitor, I don't think there's much question that osimertinib is the preferred and optimal EGFR TKI.   And so there were a couple of important factors kind of going for this trial. One is the long, long, long duration of treatment at 3 years, though with a drop-off, I think some questions about whether even that is enough, and we might be tempted to treat beyond 3 years. And then how much did the inability of most of the patients on the control arm to get osimertinib later contribute? My personal view is that it is a troubling aspect of this trial. But also so many other trials that they're run globally in places where we arguably perpetuate these disparities by running these trials that, in part, magnify the differences between the two arms because some patients just will not have access to what is our best standard of care in the U.S., or many other parts of the world, but weren't necessarily available to many of the patients on the control arm where it was conducted. So, I think that's always a concern. It's definitely an issue of this trial, but I would not say it's unique to this one.  Dr. Vamsi Velcheti: Very good points, Jack, and I completely agree with you. I think those certainly are concerns. But on the other hand, this is a pragmatic trial and that's the real-world scenario in terms of access issues, in terms of osimertinib globally, correct, in the stage 4 setting, even though we all agree that osimertinib is the best option for patients with metastatic EGFR-mutated lung cancer, I think that's obviously a reflection of global access issues and global disparities and changes in standard of care in terms of workup as well. So, it's somewhat of a pragmatic trial in some ways and I completely agree with you, I think that may have potentially had some impact on the overall survival.  Dr. Jack West: Well, I would clarify that I don't think that this really highly significant difference in overall survival is undermined completely by this. There's no question in my mind that with the huge difference in disease-free survival that we'd already seen for 3 years, it has become our standard of care really for this population at least to offer it, if not to strongly recommend it. But I would say that most of us have been quite inclined to recommend it, perhaps with caveats. And I would say that this overall survival benefit mostly corroborates that, even if there are some concerns about how these trials are done, but it's still an impressive difference that would lead me to only cement my practice of pursuing it in this setting. I just would love to re-examine how we conduct these trials and potentially potentiate disparities that exist and don't want to have our trials be more positive by capitalizing on that.   Dr. Vamsi Velcheti: Let's move on to the next abstract, LBA100; this is the KEYNOTE-671 trial. This was featured during the meeting's Clinical Science Symposium. This is a study of pembrolizumab or placebo plus platinum doublet followed by surgical resection and pembrolizumab or placebo for early-stage non-small cell lung cancer. Jack, what was the key message from this trial, and do you consider this as practice-changing?  Dr. Jack West: This has been an area where we've seen really dramatic evolution in our practice patterns, specifically, at least for patients who don't have a tumor harboring an EGFR mutation or ALK rearrangement. I would say that there has been some momentum toward preoperative neoadjuvant therapy, specifically based on the CheckMate-816 trial that gave chemo with nivolumab versus placebo and showed a significant improvement in the pathologic complete response rate at surgery as well as event-free survival. The overall survival looks encouraging but is still early and hasn't met the threshold for statistical significance, and that's FDA-approved.   But we still question whether there's a value to doing anything in the postoperative setting. And the CheckMate-816 trial did not include that as part of the trial. It allowed postoperative management at the judgment of the treating physician but didn't really prescribe anything. We now have the results of several trials in the last few months that have added a component in the postoperative setting in addition to three or four cycles of preoperative chemoimmunotherapy. And the first one that gave us a glimpse was the AEGEAN trial presented by Dr. John Heymach at AACR in April of this year that looked at chemo and durvalumab versus chemo placebo and then followed by a year of durvalumab versus placebo after surgery. That showed results in terms of major pathologic response and event-free survival that are significantly better with immunotherapy. Not clearly superior to what we would see with CheckMate-816.   And then even more recently, we saw a monthly Plenary presentation from ASCO with the Neotorch trial presented by Dr. Shun Lu of China. This was a Chinese trial only that presented results just for patients with stage 3 disease thus far. This included patients with stage 2 or stage 3, but what we saw is stage 3 results and that looked at chemo with toripalimab for 3 cycles versus placebo and then a year of checkpoint inhibitor or placebo. This also shows a benefit with the addition of immunotherapy, but not clear if that's better than what we can already achieve with neoadjuvant alone with the Checkmate-816 approach.   And then what we have now is a presentation and simultaneous publication by Dr. Heather Wakelee of KEYNOTE-671. And this is really almost the exact same trial design as AEGEAN. It's 4 cycles of platinum doublet chemotherapy and it is for patients with stage 2 to 3a disease. And this gave 4 cycles of chemotherapy with placebo or pembrolizumab. And then after surgery, patients would go on in the investigation arm to a year of pembrolizumab or to the additional year with placebo. And this shows a significant improvement in event-free survival with a hazard ratio of 0.58. It's most prominent in patients with high PD-L1, where the hazard ratio is 0.42. But there's still a benefit in patients with PD-L1 less than 1%, where it's 0.77. And there was a trend toward better overall survival here, hazard ratio of 0.73. It does not reach statistical significance at this early point. It's still preliminary but certainly looks encouraging. And there are also significant improvements in major pathologic response, where less than 10%, about a threefold difference from 30.2% with immunotherapy compared to 11% with placebo. And a very impressive improvement in pCR rate, which is 18.1% with the chemo and pembro compared to 4% with chemotherapy alone. Not surprisingly, when we look at event-free survival, it's best in the patients who achieve a pathologic complete response, but pembrolizumab improved outcomes in event-free survival even for those who didn't achieve a pCR.   The real question I would say is does the addition of a year of checkpoint inhibitor therapy postoperatively add to what we already achieve with those first three cycles with chemo-neo or 4 cycles with maybe one of these other options? And these trials can't answer that question because they just include them as a package deal. There's no way to tease apart right now the component of what incremental benefits you get from that. And it certainly adds a year of time coming in for every 3-week infusions. Even if you space that out, it's still a year of coming in and getting infusions, potential cumulative immune-related toxicities, and a lot of cost versus potentially being done. And I think that really is the big question at this point of do you want to recommend something when we don't really have a precedent for much benefit beyond the first 4 cycles? Perhaps. Certainly, we give maintenance pemetrexed and other immunotherapies and there can be benefit there. So, I wouldn't say you necessarily cap that. But if there is resistant disease after the first 4 cycles you've already given 3 cycles, how much benefit is there? How likely is it that you're going to eradicate the last cancer cells with more?   That said, I think many patients, and oncologists myself perhaps included, are going to be inclined to err on the side of possibly over-treating, but at least trying to give everything that is part of a widely studied, FDA-approved approach once these options become available. I just think it's going to end up as a careful discussion with each patient about whether they'd prefer to just say they're done or do that extra year and really feel that even if it comes back, they've done everything that made sense to try.  Dr. Vamsi Velcheti: Very good points, Jack. So let's move on to another abstract, which is the LBA9000. This is the KEYNOTE-789 trial. In my opinion, this is the most important negative phase 3 trial in lung cancer in a while. This is a trial looking at pemetrexed platinum with or without pembrolizumab in patients who have EGFR mutation-positive metastatic non-small cell lung cancer. So, what are your key takeaways, Jack?  Dr. Jack West: Well, I would say essentially we've been waiting to figure out what is the best treatment approach for patients with acquired resistance after osimertinib. And most of the patients had received osimertinib for their EGFR mutation-positive non-small cell. This is essentially KEYNOTE-189 being run in the EGFR mutation-positive patients after they've exhausted at least the major benefit of EGFR TKI therapy.   What we saw was a hazard ratio for progression-free survival of 0.8. It didn't quite make it across the threshold for efficacy, a significant difference. And so it missed that efficacy boundary. And overall survival, the hazard ratio is 0.84, also missing the efficacy boundary. When you look at the actual curves, they show modest separation, nothing eye-popping, certainly compared to some of the other trials we're talking about. But I wouldn't say they show no benefit. And I think that's, to me, why there's really still a role for a nuanced thought process and maybe some discussion about how negative this is. This is not, in my mind, stone-cold negative with no patients benefiting from immunotherapy. This is a trial that really suggests that there's a subset of patients who are benefiting from immunotherapy.   And we've also seen going back to subset analysis of the IMpower150 trial and also the ORIENT-31 trial with sintilimab and a bevacizumab biosimilar, another anti-VEGF inhibitor. These trials both really indicated a benefit in this population after EGFR TKI therapy of immunotherapy combined with VEGF. I think there could still be a value in there. I don't want to be a Pollyanna or too open-minded, but I think that there was at least a suggestion that this could still be a fruitful avenue. I think that this is still something we should do additional studies on that could bear fruit. I wouldn't close the door and categorically say this is just never going to translate to any benefit for any of these patients.   Dr. Vamsi Velcheti: The key thing, though, is, like in EGFR mutant patients I think in the previous studies as well, the response rates with single-agent PD-1 have been very minimal. And I think one of the things that's actually very important to highlight is in the operative setting, the early-stage setting, unfortunately, some of the trials with immunotherapy have included patients with an EGFR mutation. And now we have a treatment option for those patients within the adjuvant setting, especially osimertinib. We just heard from the ADAURA trial, which has a clear significant overall survival benefit. So I think it's really important to test for EGFR mutation in all stages. And if somebody with the early stage has an EGFR mutation, adjuvant immunotherapy, or perioperative immunotherapy may not be the best option for those patients.  Dr. Jack West: Right. I agree with that, although it is interesting that the KEYNOTE-671 trial did have some small population of patients with an EGFR mutation, and in that subset analysis, they seem to benefit from the pembrolizumab. I would not say that we should divert from ADAURA, but I'm just not as sure that our previous statement and mindset that immunotherapy just categorically doesn't work for patients with driver mutations is that simple.   First of all, there is some heterogeneity about which driver mutation, and the ALK-positive patients seem to really get no benefit. But I think there's still some questions about immunotherapy for EGFR. Certainly, patients with KRAS or BRAF V600E seem to benefit like the broader range of patients. And I would also say maybe it's different whether you're giving immunotherapy combined with chemotherapy versus as monotherapy. So that's why I'm just not that sure we really can characterize this that well yet.   The one additional point I would make about KEYNOTE-789 and the potential role of immunotherapy is that some experts in thoracic oncology and general oncologists alike may prefer to introduce chemotherapy at a time of progression, but keep the osimertinib going, maybe particularly for patients with brain metastases, whether current or a history of them, where we really feel that the osimertinib adds a critical component to CNS control. We don't want to ever give osimertinib or probably other EGFR TKIs concurrently with immunotherapy. So that's just a factor that we'd really want to consider when we're prioritizing where to fit in immunotherapy, if at all.  Dr. Vamsi Velcheti: Thank you, Jack. And let's move on to the next abstract, Abstract 9002. This is a pivotal study of results from the sunvozertinib, which is an EGFR exon 20 insertion site mutation drug. There's some very promising data. Jack, how do you feel this study is going to influence practice?  Dr. Jack West: Well, this is not an agent we have access to broadly yet, but I was quite impressed by it overall. I didn't mention it. We talked about it in the pre-ASCO discussion, and it was really one that I would mark as potentially practice-changing when we can get it. DZD 9008 or sunvozertinib is a potent inhibitor of exon 20 insertion mutations, and this was 97 patients, and the majority had had a couple of lines of prior therapy. They had to have gotten chemo, and the response rate was 60%, and it was really comparable efficacy with the different mutation subtypes.   I think that the main thing that I would want to clarify a little better in my own patient population is how well the drug is really tolerated. We talked about that there was not really much grade 3 toxicity and that's true, but diarrhea rates were 67%, even though it was grade 3 and just about 8%. But grade 2 diarrhea or grade 2 rash in patients who are on this therapy, we hope for a long time, I think is something we shouldn't minimize. And I think that particularly our mindset about toxicity needs to be different when we're talking about giving a treatment for 2 or 4 cycles and then being done with it versus something we hope we're going to be giving longitudinally. And we really don't want to minimize the potential impact on the quality of life of patients who are experiencing grade 2 rash, diarrhea, or paronychia for months and months, maybe more than a year at a time.   But that said, this is twice the response rate if not more than that of what we have already had for patients with this molecular aberration with an exon 20 insertion. So I think it's compelling and I think that it's going to be really valuable to offer to our patients. I just would like to clarify better how well patients who are actually on it are feeling when you incorporate the potentially chronic toxicity issues.  Dr. Vamsi Velcheti: Thank you, Jack. And let's move on to the last abstract. This the LUNAR study, LBA9005. This is a positive phase 3 study that looked at tumor-treating fields or TTF therapy with standard of care treatments in metastatic non-small-cell lung cancer following platinum failure. This has been talked about a lot at ASCO, and Jack I'm eager to hear your key takeaways about this study.  Dr. Jack West: Well, we knew from a press release several months ago, I think back in February, that there was a significant improvement in overall survival with the addition of tumor-treated fields. Again, this concept that electric fields can lead to antimitotic effect and potentially downstream induction of immunogenic cell death and enhanced immune response, that's at least the concept. And it's of course established, has utility in patients with glioblastoma, although kind of, I would say underutilized because it can be cumbersome. And I think that's one of the things we need to factor in is that this is not the easiest approach to pursue.   But we don't have that many therapies that improve overall survival significantly in previously treated patients with non-small cell lung cancer. So, I think there's good reason to focus on this and ask how beneficial it is. It was notable, it was pretty much an even split of patients enrolled on the trial, 276 patients total, but about half had gotten chemo but not gotten immunotherapy before. And then the other half, I would say the clear majority, had gotten immunotherapy as well as chemo and got docetaxel-based treatment.     And the overall survival benefit was significant for the intent to treat total population with a hazard ratio of 0.74 and a difference in 3-year survival of 18% favoring the addition of tumor-treating fields on the chest versus 7% in the patients who didn't. It really seemed to separate between the patients who had not had an immune checkpoint inhibitor and got tumor-treating fields with the checkpoint inhibitor where the hazard ratio is 0.63 and those who got tumor-treating fields with docetaxel where the hazard ratio was 0.81. So it really wasn't significant in this population.  Toxicity, no real surprises compared to what we already knew about tumor-treating fields. Mostly dermatitis, but I would say that one of the kind of unmeasured issues is that this is a device that people have to wear on their chest carrying a battery pack with them all day long. It's essentially all the waking day, and so I think that's at least cumbersome. I wouldn't call it prohibitive, but it's a challenge. And I think we need to really ask whether the juice is worth the squeeze, whether the benefit is that compelling. And I question that when we're talking about an agent that doesn't significantly move the needle against docetaxel alone.   Again, this is a population where in the U.S. we have ramucirumab to add to docetaxel. Not everyone does that. It's not uniform, but that has a statistically significant, though modest survival benefit associated with that. We don't do better than that with tumor treating fields. And so, I think that this is an option that merits discussion and some patients may opt for it, but I suspect that most of my patients would not find the absolute difference to be that compelling for the challenges it incurs. I don't know what your perspective is here.  Dr. Vamsi Velcheti: I completely agree, Jack. And I think the study design and just the fact that the standard of care has changed over the last 5, actually 6 years since the study has been open. And I'm not really so sure I could really make much sense of the data in terms of the standard of care combination with TTF providing more benefit. And I think there are more questions than answers here and I'm not so sure which populations would benefit the most. And I think, I hate to say this, but this is a nice proof of concept. I hate to say this because it's a phase 3 study and it's a positive phase 3 study, but it's clinical relevance with the current standard of care, I think, I'm not really sure how much of an impact this would really have.    Well, Jack, I've really enjoyed speaking with you about these key advances in lung cancer that were featured at the 2023 ASCO Annual Meeting. Our listeners will find links to all the studies discussed today in the transcript of this episode. Thank you so much, Jack, for joining us today.  Dr. Jack West: Always a pleasure. Thanks so much.  Dr. Vamsi Velcheti: And just like that, we've reached the end of another enriching episode. But remember, like all good things, this too must come to an end, but only until we meet again. We really would like your feedback on the podcast. If you enjoyed the podcast, please 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. Vamsidhar Velcheti   @VamsiVelcheti   Dr. H. Jack West   @JackWestMD   Follow ASCO on social media:    @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn      Disclosures:    Dr. Vamsidhar Velcheti:   Honoraria: ITeos Therapeutics   Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen, Elevation Oncology, Taiho Oncology, Merus   Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline     Dr. Jack West:   Honoraria: AstraZeneca, Genentech/Roche, Merck, Takeda, Mirati, Regneron, Amgen, Abbvie   Consulting or Advisory Role: AstraZeneca, Genentech/Roche, Merck, Takeda, Mirati Therapeutics, Regneron, Amgen, Abbvie, Summit Therapeutics   Speakers' Bureau: Takeda, Merck, AstraZeneca        

2023-02-12 Mayapura ILS Plenary Session - Global Sankirtana Presentation by HG Vaisesika Dasa by Vaisesika Dasa

A new podcast feed called Sensible Medicine is up; here is a sample of what we have to offer

The boys are back in town! Topic list: 00:00 Verbal & non-verbal communication, listening & presence 02:43 The future of social media, Zuckerberg, Elon's authenticity, Twitter & the blue checkmark disaster 10:49 Z's alleged 30-millionaire status, calculating net worth, the importance of supporting content & creators you care about 14:54 Sensible Medicine & VP's Misinformation Police article, suppression of ideas vs. presenting a better counter-argument, the far left & tribal identity 27:08 Terrible midterm election predictions, Dr. Oz's inauthenticity & subsequent loss, pseudo-science "influencers" 33:26 America's Frontline Doctors & Simone Gold's alleged implosion 35:02 Masking kids & NEJM's paper, observational vs randomized control trials, bad science & its overlap with politics, myocarditis, MedScape & the attack on Mandrola 46:30 Insulin resistance, the pros & cons of glucose monitoring as "health entertainment", metabolic health, cold plunge 1:07:53 Bob Califf tweets & long Covid claims, Ashish Jha changes his tune 1:13:36 Authenticity, being seen for who you authentically are, ZDadd tech support, post-meditation retreat realizations 1:25:23 Predictions on the approaching world shift, final thoughts Video: https://youtu.be/3Td098-gqpw Check out our new Substack collaboration, Sensible Medicine: https://sensiblemed.substack.com/ Dr. Prasad's "Plenary Session" podcast: vinayakkprasad.com/plenarysession Dr. Damania's "ZDoggMD Show" podcast: zdoggmd.com/z-blogg More info for Vinay and Zubin at https://lnk.bio/zdoggmd and vinayakkprasad.com/bio

We dive into the NYU professor who was fired cuz his class was too hard, the problems with screening for medical school admission, Dr. Glauckomfleken's maskless Twitter selfie thing and the nature of virtue signaling, why JEDI aren't woke enough according to Scientific American (cuz eugenics of course), a recent study on personality changes due to the pandemic, CRAZY liberal arts college masking policies, and much more! Video: https://youtu.be/VZW76L7nqfw Check out our new Substack collaboration, Sensible Medicine: https://sensiblemed.substack.com/ Dr. Prasad's "Plenary Session" podcast: vinayakkprasad.com/plenarysession Dr. Damania's "ZDoggMD Show" podcast: zdoggmd.com/z-blogg More info for Vinay and Zubin at https://lnk.bio/zdoggmd and vinayakkprasad.com/bio

VP and ZD celebrate the return of in-person conferences, lament the challenges of continued mandatory masking in healthcare settings, and talk about better ways to get at truth (yeah, I'm kinda phoning in the summary of this dope discussion this time, just listen already

A Labor Day special! CDC recommends bivalent Omicron-specific boosters for everyone, the madness of the CO2 meter crowd, journalism's challenges, mean attending physician comments, the evolution of language, and more! Check out our new Substack collaboration, Sensible Medicine: https://sensiblemed.substack.com/ Dr. Prasad's "Plenary Session" podcast: vinayakkprasad.com/plenarysession Dr. Damania's "ZDoggMD Show" podcast: zdoggmd.com/z-blogg More info for Vinay and Zubin at https://lnk.bio/zdoggmd and vinayakkprasad.com/bio

The saga of Dr. Leana Wen, omicron-specific boosters for the fall, low uptake for vaccinating kids

How can you determine who is trustworthy when it comes to medical information? Our new project Sensible Medicine, untangling the complexities of health care reform, angry doctor Covidian tweets with magical thinking and religiosity, the dangers of over-testing and over-treatment with regards to routine blood work, Haidt's 3 Great Untruths and cognitive distortions, pandemic response effect on true progressives, the consequences of ideological possession, how Vinay reviews the trustworthiness of sources, the difficulties of “debunking”, the monkeypox situation, and much more! Check out our new Substack collaboration, Sensible Medicine: https://sensiblemed.substack.com/ Video version: https://youtu.be/jmebULFQWyw Dr. Prasad's "Plenary Session" podcast: vinayakkprasad.com/plenarysession Dr. Damania's "ZDoggMD Show" podcast: zdoggmd.com/z-blogg More info for Vinay and Zubin at https://lnk.bio/zdoggmd and vinayakkprasad.com/bio

We deep dive into how our tribal divisions influence interpretations of science, ethics, and policy (topic list below): Omicron-specific boosters Data on severe disease prevention and booster rationale The challenges of case-control data for kids' vaccination Evidence-based morality, ethical and practical considerations around vaccine mandates Ethical and practical considerations around cooking pizza at home Does repeated COVID infection harm you Law vs. science and second order effects of legal decisions Tribal division and taking joy in the suffering of the out-group Stanford med school dean abortion letter controversy Policing language vs. real policy issues Outrage culture The abortion mess Jonathan Haidt's "Great Untruths" When Covidians turn on their own Taking offense vs. assuming good intent and how to organically promote changes in language When "science" museums behave like buttheads Loyalty on the left vs. the right Ayn Rand and young people Iodinated salt and MORE Video version: https://www.youtube.com/watch?v=9MKNQUALyWM Here's that Offit interview: https://www.youtube.com/watch?v=PLo2Wwa3NNA Dr. Prasad's "Plenary Session" podcast: vinayakkprasad.com/plenarysession Dr. Damania's "ZDoggMD Show" podcast: zdoggmd.com/z-blogg More info for Vinay and Zubin at https://lnk.bio/zdoggmd and vinayakkprasad.com/bio

Stanford medical school commencement ceremony, boosters for 5-11 year olds, Cat COVID, the end of pre-departure screening, VP's Oncology video drama, Twitter addiction and "second selfing," is continual feedback a good thing, San Francisco DA gets recalled, new immunotherapy for colorectal cancer, the importance of palliative care in oncology, and much more! Dr. Prasad's "Plenary Session" podcast: vinayakkprasad.com/plenarysession Dr. Damania's "ZDoggMD Show" podcast: zdoggmd.com/z-blogg More info for Vinay and Zubin at https://lnk.bio/zdoggmd and vinayakkprasad.com/bio

We dive into the riddle of gun violence in America, violence against healthcare professionals, public health officials and closing schools, will we need an annual COVID shot and how would we study that, the emergence of monkeypox, and the Depp/Heard trial. This episode also is available as a video: https://youtu.be/9i8cD4j4sQE Dr. Prasad's "Plenary Session" podcast: vinayakkprasad.com/plenarysession Dr. Damania's "ZDoggMD Show" podcast: zdoggmd.com/z-blogg More info for Vinay and Zubin at https://lnk.bio/zdoggmd and vinayakkprasad.com/bio

We talk with Dr. Rita Redberg (professor of medicine & cardiologist at UCSF) about how very often less is more in medical care. We cover cancer screening (PSA, mammograms, blood testing, colonoscopy, CT screening for lung cancer), the utility or lack thereof of genetic testing, medical devices, statins, hypertension guidelines and treatment, and much more! This episode also is on video: zdoggmd.com/less-is-more Dr. Prasad's "Plenary Session" podcast: vinayakkprasad.com/plenarysession Dr. Damania's "ZDoggMD Show" podcast: zdoggmd.com/z-blogg More info for Vinay and Zubin at https://lnk.bio/zdoggmd and vinayakkprasad.com/bio