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

Dr Neeraj Agarwal from the University of Utah Huntsman Cancer Institute in Salt Lake City, Dr Andrew J Armstrong from Duke Cancer Institute in Durham, North Carolina, Dr Himisha Beltran from Dana-Farber Cancer Institute in Boston, Massachusetts, Dr Fred Saad from the University of Montreal Hospital Center in Québec, Canada, and Dr Rana R McKay from the UC San Diego Moores Cancer Center discuss recent updates on available and novel treatment strategies for prostate cancer. CME information and select publications here.

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

Dr. Vivek Subbiah returns for another edition of Vivek's Takes, offering his expert insights on the standout science from the 2025 ASCO Annual Meeting. He breaks down key developments including trispecific antibodies, the growing role of radioligand therapies, a new standard of care in small cell lung cancer, and paradigm-shifting data in adjuvant therapy for colorectal cancer. The discussion also highlights a long-term exercise intervention, adjuvant vaccine studies, ctDNA and MRD integration, resistance mechanisms, artificial intelligence, and other emerging trends shaping the future of oncology. Check out Chadi's website for all Healthcare Unfiltered episodes and other content. www.chadinabhan.com/ Watch all Healthcare Unfiltered episodes on YouTube. www.youtube.com/channel/UCjiJPTpIJdIiukcq0UaMFsA

In this episode, OncLive On Air® partnered with Two Onc Docs to bring discussion of data from the phase 3 SERENA-6 trial (NCT04964934), which were presented at the 2025 ASCO Annual Meeting. SERENA-6 evaluated switching to camizestrant plus a CDK4/6 inhibitor vs continuing with a standard-of-care aromatase inhibitor plus a CDK4/6 inhibitor in the frontline setting in patients with hormone receptor–positive, HER2-negative advanced breast cancer whose tumors harbor an emergent ESR1 mutation. Drs Armstrong and Tawagi highlighted key efficacy, safety, and patient-reported outcomes from the study. They also noted the clinical implications of these findings, including how they might be currently applicable to clinical practice, as well as limitations of the research that warrant further investigation. 

Dr. Shaalan Beg and Dr. Kristen Ciombor discuss practice-changing studies in GI cancers and other novel treatment approaches that were presented at the 2025 ASCO Annual Meeting. Transcript Dr. Shaalan Beg: Hello, I'm Dr. Shaalan Beg, welcoming you to the ASCO Daily News Podcast. I'm a medical oncologist and an adjunct associate professor at UT Southwestern Medical Center in Dallas, Texas. There were some remarkable advances in gastrointestinal cancers that were presented at the 2025 ASCO Annual Meeting, and I'm delighted to be joined by Dr. Kristen Ciombor to discuss some exciting GI data. Dr. Ciombor is the Ingram Associate Professor of Cancer Research and a co-leader of Translational Research and the Interventional Oncology Research Program at the Vanderbilt Ingram Cancer Center. Our full disclosures are available in the transcript of this episode. Dr. Ciombor, it's great to have you on the podcast today. Dr. Kristen Ciombor: Thanks, Dr Beg. It's great to be here. Dr. Shaalan Beg: Alright, let's kick it off. Big year for GI cancers. We'll start off with LBA1. This was the ATOMIC study sponsored by NCI and the National Clinical Trials Network (NCTN) and the Alliance group. This is a randomized study of standard chemotherapy alone or combined with atezolizumab as adjuvant therapy for stage III mismatch repair deficient colorectal cancer. Dr. Kristen Ciombor: I think this study was really definitely practice-changing, as you can tell because it was a Plenary. But I do have some concerns in terms of how we're actually going to implement this and whether this is the final answer in this disease subtype. So, as you said, the patients were enrolled with stage III resected mismatch repair deficient colon cancer, and then they were randomized to either modified FOLFOX6 with or without atezolizumab. And that's where it starts to become interesting because not many of us give FOLFOX for 6 months like was done in this study. Obviously, the study was done over many years, so that was part of that answer, but also the patients received atezolizumab for a total of 12 months. So the question, I think, that comes from this abstract is, is this practical and is this the final answer? I do think that this is practice-changing, and I will be talking to my patients with resected mismatch repair deficient colon cancer about FOLFOX plus atezolizumab. I think the big question is, do these patients need chemotherapy? And can we do a neoadjuvant approach instead? And that's where we don't have all the answers yet. Dr. Shaalan Beg: Yeah, but it has been great to see immunotherapy make its way into the adjuvant space after having made such a big impact in the metastatic space, but still some unanswered questions in terms of the need for chemotherapy and then the duration of therapy, which I guess we'll have to stay tuned in for the next couple of years to to get a lot of those questions answered. Dr. Kristen Ciombor: Yeah, but a big congratulations to the study team, to the NCTN, the NCI. I mean, this is really a great example of federally funded research that needs to continue. So, great job by the study team. The DFS 10% difference is really very large and certainly a practice-changing study. Dr. Shaalan Beg: Yeah, and and sticking with colon cancer, and and this another federally funded study, but this time funded by a Canadian cancer clinical trials group was LBA3510. This is the CHALLENGE study. It's a randomized phase 3 trial of the impact of a structured exercise program on disease-free survival for stage III or high-risk stage II colon cancer. This study got a lot of buzz, a lot of mainstream press coverage, and a lot of discussions on what that means for us for the patients who we're going to be seeing next week in our clinic. What was your takeaway? Dr. Kristen Ciombor: Yeah, this is a really interesting study, and I was so glad to see it presented because this partially answers one of the questions that patients always have for us in clinic, right? You know, once they've completed their standard chemotherapy and surgery, what else can they do to help prevent recurrence? And so we've always known and sort of extrapolated that healthy lifestyle habits are good, but now we have data, particularly in these patients. Most of them were stage III colon cancer patients, those had high-risk stage II cancer. And basically, the goal was to increase their physical activity by at least 10 MET hours per week. So, my big question, of course, as I came into this presentation was, “Okay, what does that mean exactly? How does that translate to real life?” And really what the author presented and explained was that basically most patients could hit their target by adding a 45- to 60-minute brisk walk 3 to 4 times a week. So I think this is very approachable.  Now, in the confines of the study, this was a structured exercise program, so it wasn't just patients doing this on their own. But I do think kind of extrapolating from that, that this is very achievable for most patients. And not only did this prevent recurrence of their prior cancer, but actually the rate of new primary cancer diagnoses, was less, which is really interesting, especially in the breast and prostate cancer. So this was a really interesting, and I think practice-changing study as well, especially given that this is something that most patients can do. Dr. Shaalan Beg: Yeah, and there was a lot of discussion in the hallways after the presentation in terms of how this really changes our existing practice because most folks already recommend exercise as a way for improving outcomes in cancer patients. So we've already been doing that. Now we have some data on how much it can impact the benefit. But there was some discussion about what the actual degree of impact was. There was a drop-off rate in terms of how long folks were able to stick with this exercise regimen. But you've seen this in clinic when someone have their surgery, they have their chemotherapy, they've been so intimately involved with the oncology world, with the oncology practice, and they somehow feel that they're being let loose into this mean, angry world without any guidance and they're looking for something to do. “What more can I do in terms of my lifestyle?” And then here we have very solid data, as solid as can be for an intervention like exercise, showing that there is an impact and you can give a prescription for exercise when someone wraps up their chemotherapy for colon cancer, thanks to the study. Dr. Kristen Ciombor: Yeah. It was a great study. Dr. Shaalan Beg: Moving to gastroesophageal cancer, another late-breaking abstract. This is LBA5. The MATTERHORN trial was a phase 3 trial of durvalumab plus FLOT for resectable GE junction and gastric cancer. And again, another area where immunotherapy has made an impact, and here we're seeing it move closer for earlier-stage disease. What was your take-home for the MATTERHORN trial? Dr. Kristen Ciombor: Yeah, so this study looked at neoadjuvant perioperative durvalumab plus our current standard chemotherapy of FLOT versus placebo plus FLOT. And this was a large study, almost 1,000 patients were randomized. And the primary endpoint was event-free survival, and it was definitely met in favor of the D + FLOT arm, as Dr. Klempner discussed after Dr Janjigian's presentation. I do think there are still some unanswered questions here. Overall survival is not yet mature, so we do have to wait and see how that shakes out. But it's very interesting and kind of is reflective of what, as you said, we're looking at earlier and earlier lines of therapy, particularly with immunotherapy, in these GI cancer spaces. So it makes a lot of sense to test this and and to look at this. So the toxicity was pretty similar to what we would expect. Primary endpoint was met, but again, we'll have to wait and see what the survival data looks like. Dr. Shaalan Beg: Yeah, and in oncology, we know, especially for treatment that does add additional cost, it does add additional potential toxicity that we want to see that overall survival nudged. I did see some polls on social media asking folks whether their practices changed from this, and I think the results were favoring adding durvalumab for this group of patients but understanding that there are caveats to the addition of treatments and the eventual FDA approval in that indication as well. Dr. Kristen Ciombor: Exactly. I completely agree with that. Dr. Shaalan Beg: All right. How about we stick with gastroesophageal cancer? LBA4002 was trastuzumab deruxtecan versus ramucirumab plus paclitaxel for second-line treatment in HER2-positive unresectable or metastatic gastric cancer or GE junction cancer. This was the DESTINY-Gastric04 study. And again, antibody-drug conjugates making a big impact across different diseases. And here we have more data in the HER2-positive gastric cancer space. Your thoughts on this study? Dr. Kristen Ciombor: Yeah, so this is a really important space in gastroesophageal cancer because the HER2 positivity rate is fairly high as compared to some of our other tumor types. So, I do think one of the important things was that patients did have biopsy confirmation of HER2 status, which was very important, and then they were randomized to either T-DXd versus the kind of second-line standard of ramucirumab-paclitaxel. So this was a great practical study and really answers a question that we had for a while in terms of does anti-HER2 therapy in the second-line really impact and improve survival. So we did see a statistically significant improvement favoring T-DXd. I do think it's always important to look at toxicity, though, too. And there was about almost 14% rate of interstitial lung disease, which of course is the most feared toxicity from some of these antibody-drug conjugates, especially T-DXd. So I do think it's important to keep that in mind, but this is definitely a great addition to the armamentarium for these HER2-positive patients. Dr. Shaalan Beg: And pancreas cancer was on the stage after a very long time with a positive clinical trial. This is Abstract 4006. These were preliminary results from a phase 2 study of elraglusib in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel alone for previously untreated metastatic pancreas cancer. This is a frontline clinical trial of gemcitabine/nab-paclitaxel plus/minus the study drug. There were other cohorts in this study as well, but they reported the results of their part 3B arm. And great to see some activity in the pancreas space. And your thoughts? Dr. Kristen Ciombor: Yeah, we definitely need better treatments in pancreas cancer. This was a very welcome presentation to see. The elraglusib is an inhibitor of GSK-3beta, and it's thought that that mediates drug resistance and EMT. And so this is, I think, a perfect setting to test this drug. So patients basically were randomized. Patients with metastatic pancreas cancer were randomized 2: 1 to gemcitabine/nab-paclitaxel plus or minus this elraglusib. So, what we saw was that overall survival was better with the addition of this new drug. And overall, not only the 1-year overall survival, but also median overall survival.  The thing that was interesting, though, was that we saw that the overall survival rates were 9.3 months with the combination versus 7.2 months with just gemcitabine/nab-paclitaxel. And that's a little bit lower than we've seen in other studies. So, not sure what was going on there. Was it the patients that were a bit sicker? Was it a patient selection, you know, thing? I'm not really sure how to explain that so much. Also, the toxicity profile was much higher in terms of visual impairment, with over 60% of patients being treated with the combination versus 9% with gemcitabine/nab-paclitaxel. So these were mild, grade 1 and 2, but still something to be cautious about. Dr. Shaalan Beg: And especially with this being a phase 2 trial, making sure that in a larger study we're able to better evaluate the toxicity and see if the control arm in the larger confirmatory study performs differently will be really important before this compound makes it to the clinic in our space. But very exciting to see these kinds of results for pancreas adenocarcinoma. Dr. Kristen Ciombor: Yeah. Dr. Shaalan Beg: We've talked, it seems, a couple of times on this podcast about the BREAKWATER clinical trial. We did hear PFS and updated OS data, updated overall survival data on first-line encorafenib plus cetuximab plus modified FOLFOX6 for BRAF-mutated colorectal cancer. This was LBA3500. And eagerly anticipated results – we have all previously heard the progression-free survival results – but here we heard updated overall survival results, and very well-received study it seemed from the audience that time. So what are your takeaways on the updated results for BREAKWATER? Dr. Kristen Ciombor: In my opinion, this was one of the most practice-confirming studies. As you mentioned, we've already seen some of the preliminary data of BREAKWATER at prior meetings. But really what was particularly impactful for me was the median overall survival with the BREAKWATER regimen. So, again, patients received FOLFOX, encorafenib cetuximab in the first line if they had BRAF-mutated V600E-mutated colorectal cancer. And the median PFS was 12.8 months, which was actually really remarkable in this traditionally very aggressive, poor prognosis subtype of tumors. So, by seeing a median overall survival of 30.3 months was just incredible, in my opinion. Just a few years ago, that was considered the median overall survival for all comers for metastatic colorectal cancer. And we know the median overall survival was more in the less than 12 months range for BRAF. So this was incredibly impactful, and I think should be absolutely practice-changing for anyone who is eligible for this regimen.  I think again, where the practice meets the study is what's kind of important to think about too, how long did patients get FOLFOX, and certainly it adds toxicity to add a BRAF-targeted regimen on top of FOLFOX already. So, one of the other interesting things about the study, though, was that even though it didn't complete treatment, they actually did look at encorafenib/cetuximab alone and in the first line without chemotherapy. And those preliminary results actually looked okay, especially for patients who might not be able to tolerate chemotherapy, which we certainly see in practice. So, overall, definitely more data. And I agree that it's certainly practice-changing. Dr. Shaalan Beg: And it completely, as you mentioned, changes the outlook for a person who's diagnosed with BRAF-mutated metastatic colon cancer today versus even 7 or 8 years ago. Dr. Kristen Ciombor: And we're seeing this over and over in other subtypes too, but how you choose to treat the patient up front really matters. So really giving the right regimen up front is the key here. Dr. Shaalan Beg: And along the same lines, Abstract 3501 wanted to answer the question on whether people with MSI-high metastatic colorectal cancer need double checkpoint inhibitor therapy or is single therapy enough. So this [CheckMate-8HW] study compared nivo plus ipi with nivo alone, nivo monotherapy for MSI-high metastatic colorectal cancer. And we've known that both of these are fairly active regimens, but we also know the chance of immune-related adverse events is significantly higher with combination therapy. So this was a much-needed study for this group of patients. And what were your takeaways here? Dr. Kristen Ciombor: This, of course, has been really nivo-ipi in the first-line MSI-high metastatic colorectal cancer is now a standard of care. And not everybody is eligible for it, and there could be reasons, toxicity reasons, and other things too. But as we've been seeing for the last couple of years, immunotherapy clearly beats chemo in this space. And now looking at doublet versus single immunotherapy treatment in the first line, I think really nivo-ipi does beat out monotherapy. I will say, however, there is a caveat in that we still haven't seen the nivo-ipi versus nivo in the first line. So what has been presented thus far has been across all lines of therapy, and that does muddy the waters a little bit. So definitely looking forward and and we've asked this many times and based on the statistical plan and and what not, you know, we just haven't seen that data yet. But I do think it's becoming increasingly important to consider doublet immunotherapy for these patients as long as there are no contraindications. With the again, with the caveat that we have to have these toxicity discussions in the clinic with patients because many patients can tolerate it, you know, this regimen fairly well, but there can be very severe toxicities. So, I think an informed discussion should really be had with each patient before moving forward. Dr. Shaalan Beg: Yeah, informed decision, making them aware of the potential of real significant toxicities, immune-related toxicities with double therapy. But I am curious in your practice, how often do you see people choosing doublet therapy as frontline? Dr. Kristen Ciombor: So patients are really savvy, and a lot of times they've heard this data before or have come across it in patient advocacy groups and other things, and it's really nice to be able to have that conversation of the risk versus benefit. So I will say not all of my patients choose doublet, and many of them are still cured with immunotherapy monotherapy. So the big question there is, will we ever understand who actually needs the doublet versus who can still be cured or have very good long-term outcomes with just the single agent? And that has not been answered yet. Dr. Shaalan Beg: What a great point. So the last abstract I was hoping we could talk about is POD1UM-303 or the INTERAACT2 subgroup analysis and impact of delayed retifanlimab treatment for patients with squamous cell carcinoma of the anal canal. What were your thoughts here? Dr. Kristen Ciombor: This was a study, actually we saw at ESMO, we saw the primary data at ESMO last year, and this was an update with some exploratory analyses. But this was really an important study because once again, we're looking at immunotherapy in later lines of therapy. That's how we started looking at and investigating immunotherapy, and now we're moving it up and up in the treatment course. So this was a study of carboplatin/paclitaxel plus or minus retifanlimab. Actually it was retifanlimab versus placebo. And it was a positive study, as we heard last year. This actually led to FDA approval of this regimen last month, just before ASCO, and it has now been incorporated in the NCCN guidelines as the preferred first-line option.  So what I thought was important from the additional data presented at ASCO was looking at the different subgroups, it did not appear that patients with liver mets or not had different outcomes. So that was really good to see because sometimes in colon cancer we see that immunotherapy doesn't work as well when patients have liver mets. And interestingly, because we use immunotherapy in anal cancer without any biomarkers, unlike with colon cancer or some of the other tumor types, also the authors looked at PD-L1 status, and it did look like maybe patients did a little bit better if they had higher PD-L1 expression, but patients still could benefit even if they were PD-L1 negative. So that was important, I think, and we will continue to see further data come out from this study. I want to mention also that EA2176 just completed accrual, so that was carbo-taxol plus or minus nivolumab. And so we should be seeing that data sometime soon, which will hopefully also confirm the ongoing role for immunotherapy in the first-line setting for anal cancer. Dr. Shaalan Beg: That was a fantastic review. Thank you, Dr Ciombor. Thanks for sharing your valuable insights with us today on the ASCO Daily News Podcast. Dr. Kristen Ciombor: Thanks for having me here. Dr. Shaalan Beg: And thank you to our listeners for your time today. You will find links to the abstracts discussed today in the transcript of this episode. And 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. 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. Shaalan Beg  @ShaalanBeg  Dr. Kristen Ciombor @KristenCiombor Follow ASCO on social media:    @ASCO on Twitter   @ASCO on BlueSky  ASCO on Facebook    ASCO on LinkedIn    Disclosures:   Dr. Shaalan Beg:   Consulting or Advisory Role: Ipsen, Cancer Commons, Foundation Medicine, Science37, Nant Health, Lindus Health Speakers' Bureau: Sirtex Research Funding (Inst.): Delfi Diagnostics, Universal Diagnostics, Freenome Dr. Kristen Ciombor: Consulting or Advisory Role: Pfizer, Incyte, Exelixis, Bayer, ALX Oncology, Tempus, Agenus, Taiho Oncology, Merck, BeiGene Research Funding (Inst.): Pfizer, Boston Biomedical, MedImmune, Onyx, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Merck, Novartis, Incyte, Amgen, Sanofi, Bristol-Myers Squibb, Array BioPharma, Incyte, Daiichi Sankyo, Nucana, Abbvie, Merck, Pfizer/Calthera, Genentech, Seagen, Syndax Travel, Accommodations, Expenses: Incyte, Tempus

Dr. Allison Zibelli and Dr. Rebecca Shatsky discuss advances in breast cancer research that were presented at the 2025 ASCO Annual Meeting, including a potential new standard of care for HER2+ breast cancer, the future of ER+ breast cancer management, and innovations in triple negative breast cancer therapy. Transcript Dr. Allison Zibelli: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Allison Zibelli, your guest host of the podcast today. I'm an associate professor of medicine and a breast medical oncologist at the Sidney Kimmel Comprehensive Cancer Center at Jefferson Health. There was a substantial amount of exciting breast cancer data presented at the 2025 ASCO Annual Meeting, and I'm delighted to be joined by Dr. Rebecca Shatsky today to discuss some of these key advancements. Dr. Shatsky is an associate professor of medicine at UC San Diego and the head of breast medical oncology at the UC San Diego Health Moores Cancer Center, where she also serves as the director of the Breast Cancer Clinical Trials Program and the Inflammatory and Triple-Negative Breast Cancer Program.  Our full disclosures are available in the transcript of this episode. Dr. Shatsky, it's great to have you on the podcast today. Dr. Rebecca Shatsky: Thanks, Dr. Zibelli. It's wonderful to be here. Dr. Allison Zibelli: So, we're starting with DESTINY-Breast09, which was trastuzumab deruxtecan and pertuzumab versus our more standard regimen of taxane, trastuzumab pertuzumab for first-line treatment of metastatic HER2-positive breast cancer. Could you tell us a little bit about the study? Dr. Rebecca Shatsky: Yeah, absolutely. So, this was a long-awaited study. When T-DXd, or trastuzumab deruxtecan, really hit the market, a lot of these DESTINY-Breast trials were started around the same time. Now, this was a global, randomized, phase 3 study presented by Dr. Sara Tolaney from the Dana-Farber Cancer Institute of Harvard in Boston. It was assessing essentially T-DXd in the first-line setting for metastatic HER2-positive breast cancer in addition to pertuzumab. And that was randomized against our standard-of-care regimen, which was established over a decade ago by the CLEOPATRA trial, and we've all been using that internationally for at least the past 10 years. So, this was a large trial, and it was one-to-one-to-one of patients getting T-DXd plus pertuzumab, T-DXd alone, or THP, which mostly is used as docetaxel and trastuzumab and pertuzumab every three weeks for six cycles. And this was in over 1,000 patients; it was 1,159 patients with metastatic HER2-positive breast cancer. This was a very interesting trial. It was looking at the use of trastuzumab deruxtecan, but patients were started on this treatment for their first-line metastatic HER2-positive breast cancer with no end date to their T-DXd. So, it was, you know, you were started on T-DXd every 3 weeks until progression. Now, CLEOPATRA is a little bit different than that, though, as we know. So, CLEOPATRA has a taxane plus trastuzumab and pertuzumab. But generally, patients drop the taxane after about six to seven cycles because, as we know, you can't be really on a taxane indefinitely. You get pretty substantial neuropathy as well as cytopenias, other things that end up happening. And so, in general, that regimen has sort of a limited time course for its chemotherapy portion, and the patients maintained after the taxane is dropped on their trastuzumab and their pertuzumab, plus or minus endocrine therapy if the investigator so desires. And the primary endpoint of the trial was progression-free survival by blinded, independent central review (BICR) in the intent-to-treat population. And then it had its other endpoints as overall survival, investigator-assessed progression-free survival, objective response rates, and duration of response, and of course, safety. As far as the results of this trial, so, I think that most of us key opinion leaders in breast oncology were expecting that this was going to be a positive trial. And it surely was. I mean, this is a really, really active drug, especially in HER2-positive disease, of course. So, the DESTINY-Breast03 data really established that, that this is a very effective treatment in HER2-positive metastatic breast cancer. And this trial really, again, showed that. So, there were 383 patients that ended up on the trastuzumab plus deruxtecan plus pertuzumab arm, and 387 got THP, the CLEOPATRA regimen. What was really interesting also to note of this before I go on to the results was that 52% of patients on this trial had de novo metastatic disease. And that's pretty unusual for any kind of metastatic breast cancer trial. It kind of shows you, though, just how aggressive this disease is, that a lot of patients, they present with de novo metastatic disease. It's also reflecting the global nature of this trial where maybe the screening efforts are a little bit less than maybe in the United States, and more patients are presenting as later stage because to have a metastatic breast cancer trial in the United States with 52% de novo metastatic disease doesn't usually happen. But regardless, the disease characteristics were pretty well matched between the two groups. 54% of the patients were triple positive, or you could say hormone-positive because whether they were PR positive or ER positive and PR negative doesn't really matter in this disease. And so, the interim data cutoff was February of this year, of 2025. So, the follow-up so far has been about 29 months, so the data is still really immature, only 38% mature for progression-free survival interim analysis. But what we saw is that T-DXd plus pertuzumab, it really improved progression-free survival. It had a hazard ratio that was pretty phenomenal at 0.56 with a confidence interval that was pretty narrow of 0.44 to 0.71. So, very highly statistically significant data here. The progression-free survival was consistent across all subgroups. Overall survival, very much immature at this time, but of course, the trend is towards an overall survival benefit for the T-DXd group. The median durable response with T-DXd plus pertuzumab exceeded 3 years. Now, importantly, though, I want to stress this, is grade 3 or above treatment-emergent adverse events occurred in both subgroups pretty equally. But there were 2 deaths in the T-DXd group due to interstitial lung disease. And there was a 12.1% adjudicated drug-induced interstitial lung disease/pneumonitis event rate in the T-DXd group and only 1%, and it was grade 1-2, in the THP group. So, that's really the caveat of this therapy, is we know that a percentage of patients are going to get interstitial lung disease, and that some may have very serious adverse events from it. So, that's always something I keep in the back of my mind when I treat patients with T-DXd. And so, overall, the conclusions of the trial were pretty much a slam dunk. T-DXd plus pertuzumab, it had a highly statistically significant and clinically meaningful improvement in progression-free survival versus the CLEOPATRA regimen. And that was across all subgroups for first-line metastatic HER2-positive breast cancer here. And so, yeah, the data was pretty impressive. Just to go into the overall response rate, because that's always super important as well, you had 85.1% of patients having a confirmed overall RECIST response rate in the T-DXd plus pertuzumab group and a 78.6 in the CLEOPATRA group. The complete CR rate, complete response was 15.1% in the T-DXd group and 8.5 in the CLEOPATRA regimen. And it was really an effective regimen in this group, of course. Dr. Allison Zibelli: So, the investigators say at the end of their abstract that this is the new standard of care. Would you agree with that statement? Dr. Rebecca Shatsky: Yeah, that was a bold statement to make because I would say in the United States, not necessarily at the moment because the quality of life here, you have to think really hard about. Because one thing that's really important about the DESTINY-Breast09 data is that this was very much an international trial, and in many of the countries where patients enrolled on this, they were not able to access T-DXd off trial. And so, for them, this means T-DXd now or potentially never. And so, that is a really big difference whereas internationally, that may mean standard of care. However, in the US, patients have no issues accessing T-DXd in the second- or third-line settings. And right now, it's the standard of care in the second line in the United States, with all patients basically getting this second-line therapy except for some unique patients where they may be doing a PATINA trial regimen, which we saw at San Antonio Breast Cancer in 2024 of the triple-positive patients getting hormonal therapy plus palbociclib, which had a really great durable response. That was super impressive as well. Or there is the patient that the investigator can pick KADCYLA because the patient really wants to preserve their hair or maybe it's more indolent disease. But the quality of life on T-DXd indefinitely in the first-line setting is a big deal because, again, that CLEOPATRA regimen allows patients to drop their chemotherapy component about five to six months in. And with this, you're on a drug that feels very chemo-heavy indefinitely. And so, I think there's a lot more to investigate as far as what we're going to do with this data in the United States because it's a lot to commit a patient in the first-line metastatic setting. These de novo metastatic patients, some of them may be cured, honestly, on the HER2-targeting regimen. That's something we see these days. Dr. Allison Zibelli: So, very interesting trial. I'm sure we'll be talking about this for a long time.  So, let's move on to SERENA-6, which was, I thought, a very interesting trial. This trial took patients with ER positive, advanced breast cancer after six months on an AI (aromatase inhibitor) and a CDK4/6 inhibitor. They did ctDNA every two to three months, and when they saw an ESR1 mutation emerge, they changed half of the patients to camizestrant plus CDK4/6 and kept the other half on the AI plus CDK4/6. Can you talk about that trial a little bit, please? Dr. Rebecca Shatsky: Yeah, so this was a big trial at ASCO25. This was presented as a Plenary Session. So, this was camizestrant plus a CDK4/6 inhibitor, and it could have been any of the three, so palbo, ribo, or abemaciclib in the first-line metastatic hormone-positive population, and patients were on an AI with that. They were, interestingly, tested by ctDNA at baseline to see if they had an ESR1 mutation. So, that was an interesting feature of this trial. But patients had to have already been on their CDK4/6 inhibitor plus AI for at least 6 months to enroll. And then, as you mentioned, they got ctDNA testing every 2 to 3 months. This was also a phase 3, double-blind, international trial. And I do want to highlight again, international here, because that's important when we're considering some of this data in the U.S. because it influences some of the results. So, this was presented by Dr. Nick Turner of the Royal Marsden in the UK. So, just a little bit of background for our listeners on ESR1 mutations and why they're important. This is the most common, basically, acquired resistance mutation to patients being treated with aromatase inhibitors. We know that treatment with aromatase inhibitors can induce this. It makes a conformational change in the estrogen receptor that makes the estrogen receptor constitutively active, which allows the cell to signal despite the influence of the aromatase inhibitor to decrease the estrogen production so that the ligand binding doesn't matter as much as far as the cell signaling and transcription is concerned. And camizestrant, you know, as an oral SERD, just to explain that a little bit too; these are estrogen receptor degraders. The first-in-class of a selective estrogen receptor degrader to make it to market was fulvestrant. And that's really been our standard-of-care estrogen degrader for the past 25 years, almost 25 years. And so, a lot of us are just looking for some of these oral SERDs to replace that. But regardless, they do tend to work in the ESR1-mutated population. And we know that patients on aromatase inhibitors, the estimates of patients developing an ESR1 mutation, depending on which study you look at, somewhere between 30% to 50% overall, patients will develop this mutation with hormone-positive metastatic breast cancer. There is a small percentage of patients that have these at baseline without even treatment of an aromatase inhibitor. The estimates of that are somewhere between 0.5 and up to 5%, depending on the trial you look at and the population. But regardless, there is a chance someone on their CDK4/6 inhibitor plus AI at 6 months' time course could have had an ESR1 mutation at that time. But anyway, so they got this ctDNA every 2 to 3 months, and once they were found to develop an ESR1 mutation, the patients were then switched to the oral SERD. AstraZeneca's version of the oral SERD is camizestrant, 75 mg daily. And then their type of CDK4/6 inhibitor was maintained, so they didn't switch the brand of their CDK4/6 inhibitor, importantly. And that was looked at then for progression-free survival, but these were patients with measurable disease by RECIST version 1.1. And the data cut off here was November of 2024. This was a big trial, you know, and I think that that's influential here because this was 3,256 patients, and that's a lot of patients. So, they were all eligible. And then 315 patients ended up being randomized to switch to camizestrant upon presence of that ESR1 mutation. So, that was 157 patients. And then the other half, so they were randomized 1:1, they continued on their AI without switching to an oral SERD. That was 158 patients. They were matched pretty well. And so, their baseline characteristics, you know, the two subgroups was good. But this was highly statistically significant data. I'm not going to diminish that in any way. Your hazard ratio was 0.44. Highly statistically significant confidence intervals. And you had a median progression-free survival in those that switched to camizestrant of 16 months, and then the non-switchers was 9.2 months. So, the progression-free survival benefit there was also consistent across the subgroups. And so, you had at 12 months, the PFS rate was 60.7% for the non-treatment group and 33.4% in the treatment group. What's interesting, though, is we don't have overall survival data. This is really immature, only 12% mature as far as overall survival. And again, because this was an international trial and patients in other countries right now do not have the access to oral SERDs that the United States does, the crossover rate, they were not allowed to crossover, and so, a very few patients, when we look at progression-free survival 2 and ultimately overall survival, were able to access an oral SERD in the off-trial here and in the non-treatment group. And so, that's really important as far as we look at these results. Adverse events were pretty minimal. These are very safe drugs, camizestrant and all the other oral SERDs. They have some mild toxicities. Camizestrant is known for something weird, which is called photopsia, which is some flashing lights in the periphery of the eye, but it doesn't seem to have any serious clinical significance that we know of. It has a little bit of bradycardia, but it's otherwise really well tolerated. You know, I hate to say that because that's very subjective, right? I'm not the one taking the drug. But it doesn't have any serious adverse events that would cause discontinuation. And that's really what we saw in the trial. The discontinuation rates were really low. But overall, I mean, this was a positive trial. SERENA-6 showed that switching to camizestrant at the first sign of an ESR1 mutation on CDK4/6 inhibitor plus AI improved progression-free survival. That's all we can really say from it right now. Dr. Allison Zibelli: So, let's move on to ASCENT-04, which was a bit more straightforward. Sacituzumab govitecan plus pembrolizumab versus chemotherapy plus pembrolizumab in PD-L1-positive, triple-negative breast cancer. Could you talk about that study? Dr. Rebecca Shatsky: Yeah, so this was also presented by the lovely Sara Tolaney from Dana-Farber. And this study made me really excited. And maybe that's because I'm a triple-negative breast cancer person. I mean, not to say that I don't treat hundreds of patients with hormone- positive, but our unmet needs in triple negative are huge because this is a disease where you have got to throw your best available therapy at it as soon as you can to improve survival because survival is so poor in this disease. The average survival with metastatic triple-negative breast cancer in the United States is still 13-18 months, and that's terrible. And so, for full disclosure, I did have this trial open at my site. I was one of the site PIs. I'm not the global PI of the study, obviously. So, what this study was was for patients who had had at least a progression-free survival of 6 months after their curative intent therapy or de novo metastatic disease. They were PD-L1 positive as assessed by the Dako 22C3 assay of greater than or equal to a CPS score of 10. So, that's what the KEYNOTE-355 trial was based on as well. So, standard definition of PD-L1 positive in breast cancer here. And basically, these patients were randomized 1:1 to either their sacituzumab govitecan plus pembrolizumab, day 1 they got both therapies, and then day 8 just the saci, as is standard for sacituzumab. And then the other group got the KEYNOTE-355 regimen. So, that is pembrolizumab with – your options are carbogem there, paclitaxel or nab-paclitaxel. And it's up to investigator's decision which upon those they decided. They followed these patients for disease progression or unacceptable toxicity. It was really an impressive trial in my opinion because we know already that this didn't just improve progression-free survival, because survival is so poor in this disease, of course, we know that it improved overall survival. It's trending towards that very much, and I think that's going to be shown immediately. And then the objective response rates were better, which is key in this disease because in the first-line setting, you've got a lot of people who, especially your relapsed TNBC that don't respond to anything. And you lose a ton of patients even in the first-line setting in this disease. And so, this was 222 patients to chemotherapy and pembro and 221 to sacituzumab plus pembro. Median follow-up has only been 14 months, so it's still super early here. Hazard ratio so far of progression-free survival is 0.65, highly statistically significant, narrow confidence intervals. And so, the median duration of response here for the saci group was 16.5 months versus 9.2 months. So, you're getting a 7-month progression-free survival benefit here, which in triple negative is pretty fantastic. I mean, this reminds me of when we saw the ASCENT data originally come out for sacituzumab, and we were all just so happy that we had this tool now that doubled progression-free and overall survival and made such a difference in this really horrible disease where patients do poorly. So, OS is technically immature here, but it's really trending very heavily towards improvement in overall survival. Importantly, the treatment-related adverse events in this, I mean, we know sacituzumab causes neutropenia, people who are experienced with this drug know how to manage it at this point. There wasn't any really unexpected treatment-related adverse events. You get some people with sacituzumab who have diarrhea. It's usually pretty manageable with some Imodium. So, it was cytopenias predominantly in this disease in this population that were highlighted as far as adverse events. But I'm going to be honest, like I was surprised that this wasn't the plenary over the SERENA-6 data because this, in my mind, there we have a practice-changing trial. I will immediately be trying to use this in my PD-L1 population because, to be honest, as a triple-negative breast cancer clinical specialist, when I get a patient with metastatic triple-negative breast cancer who's PD-L1 positive, I think, "Oh, thank God," because we know that part of the disease just does better in general. But now I have something that really could give them a durable response for much longer than I ever thought possible when I started really heavily treating this disease. And so, this was immediately practice-changing for me. Dr. Allison Zibelli: I think that it's pretty clear that this is at least an option, if not the option, for this group of patients. Dr. Rebecca Shatsky: Yeah, the duration of responses here was – it's just really important because, I mean, I do think this will make people live longer. Dr. Allison Zibelli: So, moving on to the final study that we're going to discuss today, neoCARHP (LBA500), which was neoadjuvant taxane plus trastuzumab, pertuzumab, plus or minus carbo(platin) in HER2-positive early breast cancer. I think this is a study a lot of us have been waiting for. What was the design and the results of this trial? Dr. Rebecca Shatsky: I was really excited about this as well because I'm one of those people that was waiting for this. This is a Chinese trial, so that is something to take note of. It wasn't an international trial, but it was a de-escalation trial which had become really popular in HER2-positive therapy because we know that we're overtreating HER2-positive breast cancer in a lot of patients. A lot of patients we're throwing the kitchen sink at it when maybe that is not necessary, and we can really de-escalate and try to personalize therapy a little bit better because these patients tend to do well. So, the standard of care, of course, in HER2-positive curative intent breast cancer with tumors that are greater than 2 cm is to give them the TCHP regimen, which is docetaxel, carboplatin, trastuzumab, and pertuzumab. And that was sort of established by several trials in the NeoSphere trial, and now it's been repeated in a lot of different studies as well. And so, that's really the standard of care that most people in the United States use for HER2-positive curative intent breast cancer. This was a trial to de-escalate the carboplatin, which I was super excited about because many of us who treat this disease a lot think carbo is the least important part of the therapy you're giving there. We don't really know that it's necessary. We've just been doing it for a long time, and we know that it adds a significant amount of toxicity. It causes thrombocytopenia, it causes severe nausea, really bad cytopenias that can be difficult in the last few cycles of this to manage. So, this trial was created. It randomized patients one to one with stage 2 and 3 HER2-positive breast cancer to either get THP, a taxane, pertuzumab, trastuzumab, similar to the what we do in first-line metastatic HER2-positive versus the whole TCHP with a carboplatin AUC of 6, which is what's pretty standard. And it was a non-inferiority trial, so important there. It wasn't to establish superiority of this regimen, which none of us, I think, were looking for it to. And it was a modified intent-to-treat population. And so, all patients got at least one cycle of this to be assessed as a standard for an intent-to-treat trial. And so, they assumed a pCR rate of about 62.8% for both groups. And, of course, it included both HER2-positive triple positives and ER negatives, which are, you know, a bit different diseases, to be honest, but we all kind of categorize them and treat them the same. And so, this trial was powered appropriately to detect a non-inferiority difference. And so, we had about 380 patients treated on both arms, and there was an absolute difference of only 1.8% of those treated with carbo versus those without. Which was fantastic because you really realized that de-escalation here may be something we can really do. And so, the patients who got, of course, the taxane regimen had fewer adverse events. They had way fewer grade 3 and 4 adverse events than the THP group. No treatment-associated deaths occur, which is pretty standard for- this is a pretty safe regimen, but it causes a lot of hospitalizations due to diarrhea, due to cytopenias, and neutropenic fever, of course. And so, I thought that this was something that I could potentially enact, you know, and be practice-changing. It's hard to say that when it's a trial that was only done in China, so it's not necessarily the United States population always. But I think for patients moving forward, especially those with, say, a 2.5 cm tumor, you know, node negative, those, I'd feel pretty comfortable not giving them the carboplatin here. Notes that I want to make about this population is that the majority were stage 2 and not stage 3. They weren't necessarily your inflammatory HER2-positive breast cancer patients. And that the taxane that was utilized in the trial is a little different than what we use in the United States. The patients were allowed to get nab-paclitaxel, which we don't have FDA approval for in the first-line curative intent setting for HER2-positive breast cancer in the United States. So, a lot of them got abraxane, and then they also got paclitaxel. We tend to use docetaxel every 3 weeks in the United States. So, just to point out that difference. We don't really know if that's important or not, but it's just a little bit different to the population we standardly treat. Dr. Allison Zibelli: So, are there patients that you would still give TCHP to? Dr. Rebecca Shatsky: Yeah, great question. I've been asked that a lot in the past like week since ASCO. I'd say in my inflammatory breast cancer patients, that's a group I do tend to sometimes throw the kitchen sink at. Now, I don't actually use AC in those because I know that that was the concern, but I think the TRAIN-2 trial really showed us you don't need to use Adriamycin in HER2-positive disease unless it's like refractory. So, I don't know that I would throw this on my stage 3C or inflammatory breast cancer patients yet because the majority of this were not stage 3. So, in your really highly lymph node positive patients, I'm a little bit hesitant to de-escalate them from the start. This is more of a like, if there's serious toxicity concerns, dropping carbo is absolutely fine here. Dr. Allison Zibelli: All right, great.  Thank you, Dr. Shatsky, for sharing your valuable insights with us on the ASCO Daily News Podcast today. Dr. Rebecca Shatsky: Thanks so much, Dr. Zibelli and ASCO Daily News. I really want to thank you for inviting me to talk about this today. It was really fun, and I hope you find my opinions on some of this valuable. And so, I just want to thank everybody and my listeners as well. Dr. Allison Zibelli: And thank you to our listeners for joining us today. You'll find the links to all the abstracts discussed today in the transcript of this episode. Finally, if you like this podcast and you learn things from it, please take a moment to rate, review, and describe because it helps other people find us wherever you get your podcasts. Thank you again. 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. Allison Zibelli Dr. Rebecca Shatsky @Dr_RShatsky Follow ASCO on social media:  @ASCO on Twitter  @ASCO on Bluesky  ASCO on Facebook  ASCO on LinkedIn   Disclosures: Dr. Allison Zibelli: No relationships to disclose Dr. Rebecca Shatsky: Consulting or Advisory Role: Stemline, Astra Zeneca, Endeavor BioMedicines, Lilly, Novartis, TEMPUS, Guardant Health, Daiichi Sankyo/Astra Zeneca, Pfizer Research Funding (Inst.): OBI Pharma, Astra Zeneca, Greenwich LifeSciences, Briacell, Gilead, OnKure, QuantumLeap Health, Stemline Therapeutics, Regor Therapeutics, Greenwich LifeSciences, Alterome Therapeutics  

Featuring perspectives from Prof Nicolas Girard, Dr Jonathan Goldman, Dr Pasi A Jänne, Dr Suresh S Ramalingam, Dr Joshua K Sabari and Dr Helena Yu, moderated by Dr Yu, including the following topics: Introduction (0:00) Evolving First-Line Treatment for Metastatic EGFR Mutation-Positive Non-Small Cell Lung Cancer (NSCLC) — Dr Yu (1:47) EGFR-Targeted Approaches for Relapsed EGFR-Mutant NSCLC; Strategies to Facilitate Delivery of Recently Approved Agents — Dr Sabari (23:48) Potential Utility of TROP2-Targeted Therapy in the Management of EGFR-Mutant NSCLC — Dr Ramalingam (45:16) Contemporary Care for Patients with Nonmetastatic EGFR-Mutant NSCLC — Dr Goldman (1:03:56) Current and Future Management of EGFR Exon 20 Mutation-Positive NSCLC — Prof Girard (1:24:40) Emerging Role of HER3-Targeted Therapy in the Management of EGFR-Mutant NSCLC — Dr Jänne (1:43:46) CME information and select publications

Dr. John Sweetenham and Dr. Marc Braunstein highlight top research on hematologic malignancies from the 2025 ASCO Annual Meeting, including abstracts on newly diagnosed chronic phase CML, relapsed B-cell lymphoma, and multiple myeloma. Transcript Dr. John Sweetenham: Hello, and welcome to the ASCO Daily News Podcast. I'm your host, Dr. John Sweetenham. On today's episode, we'll be discussing promising advances in newly diagnosed chronic phase CML, relapsed B-cell lymphoma, multiple myeloma, and other hematologic malignancies that were presented at the 2025 ASCO Annual Meeting. Joining me for this discussion is Dr. Marc Braunstein, a hematologist and oncologist at the NYU Perlmutter Cancer Center. Our full disclosures are available in the transcript of this episode.  Marc, there were some great studies in the heme space at this year's Annual Meeting, and it's great to have you back on the podcast to highlight some of these advances. Dr. Marc Braunstein: Yes, I agree, John, and thank you so much for inviting me again. It's great to be here.  Dr. John Sweetenham: Let's start out with Abstract 6501. This was a study that reported on the primary endpoint results of the phase 3B ASC4START trial, which assessed asciminib versus nilotinib in newly diagnosed chronic phase CML. And the primary endpoint of this, as you know, was time to treatment discontinuation because of adverse events. Can you give us your insights into this study? Dr. Marc Braunstein: Absolutely. So, like you mentioned, you know, asciminib is an allosteric inhibitor of the BCR-ABL kinase that has activity in CML, and that includes patients with the T315I mutation that confers resistance to first- and second-generation TKIs. So, the ASC4FIRST study, which was published last year in the New England Journal of Medicine, showed superior efficacy of asciminib compared to investigator-selected first- or second-generation TKIs, actually leading to the FDA approval of asciminib in first-line CML. So, the authors of that study presented data at this year's ASCO meeting from the phase 3 ASC4START comparing safety and time to discontinuation due to adverse events of asciminib versus nilotinib, a second-generation TKI. So, 568 patients with newly diagnosed CML were randomized one-to-one to once-daily asciminib or twice-daily nilotinib. So, at a median follow-up of 9.7 months, about 11% in the asciminib group and 17% in the nilotinib group discontinued treatment, with significantly fewer discontinuations with asciminib due to adverse events. There was also a secondary endpoint of major molecular response, which was also better with asciminib. For example, the MR 4.5, which is a deep response, was 2.5% versus 0.4% favoring asciminib by week 12. So, I think in conclusion, these results build on the ASC4FIRST study, making the case for the superior safety and efficacy of asciminib versus other first- or second-generation TKIs in newly diagnosed CML. Dr. John Sweetenham: Thanks, Marc. Do you think this is going to change practice? Dr. Marc Braunstein: I think so. I think there are still some questions to be answered, such as what resistance mutations occur after first-line treatment with asciminib. But I think the sum of these studies really make the case for using asciminib upfront in CML. Dr. John Sweetenham: Okay, great. Thank you. And let's move on to our second abstract. This was Abstract 7015 and was reported from Mass General Hospital. And this was a study in patients with relapsed and refractory diffuse large B-cell lymphoma and reported the 2-year results of the so-called STARGLO study. This is a comparison of glofitamab, a T-cell engaging bispecific antibody, with gemcitabine and oxaliplatin in this group of patients. Can you tell us a little bit about your impressions of this study? Dr. Marc Braunstein: Absolutely. So just for background, the treatment landscape for relapsed/refractory large B-cell lymphoma is expanding, now with two bispecific antibodies targeting CD20 that are approved after two or more lines of therapy. Among these, glofitamab was approved in 2023 based on phase 2 data showing an objective response rate of 52%, with 39% complete responses in relapsed/refractory large B-cell lymphoma patients after a median of three prior lines of therapy. Distinguishing glofitamab from epcoritamab, the other approved bispecific, glofitamab was given for 12 cycles and then stopped. Additionally, when combined with gemcitabine and oxaliplatin in the phase 3 STARGLO study, there was significantly improved overall survival compared to rituximab plus gemcitabine and oxaliplatin in transplant-ineligible relapsed/refractory large B-cell lymphoma patients at a median follow-up of 11 months.  The authors of that study published last year in Lancet now present at ASCO this year the 2-year follow-up of the STARGLO study. Two hundred and seventy-four patients with a median of one prior line of therapy were randomized two-to-one to glofitamab plus GemOx versus rituximab plus GemOx, with the primary endpoint of overall survival. Here, the median overall survival was not reached versus 13.5 months, with a median PFS also significantly improved at about 14 months versus 4 months in the control. CRS of note in the glofitamab arm was mostly grade 1 or 2, with only about 2.3% grade 3 events. And three of the four patients had grade 1 or 2 neurotoxicity. So, John, putting this into context, I think it's encouraging that we now have randomized data showing the superiority of a bispecific plus chemotherapy over rituximab plus chemotherapy in transplant-ineligible patients. And while only 8% of the patients in the STARGLO study had prior anti-CD19 CAR T-cell therapy, I think this regimen could be considered in those patients who are ineligible for transplant or CAR T-cell therapy. Dr. John Sweetenham: Yeah, I agree. I think a couple of other compelling numbers to me were the fact that around 55% of these patients were alive at 2 years in the group who'd received glofitamab, and that almost 90% of those having that arm of the study who had a CR at the end of treatment were alive at 12 months. So, clearly, it's an active agent and also a kind of great off-the-shelf fixed-duration alternative in these relapsed and refractory patients. Dr. Marc Braunstein: I agree, and I would also note that the phase 3 SKYGLO study is looking at glofitamab plus Pola-R-CHP versus Pola-R-CHP alone. So, we may even be using these eventually in the first-line setting. Dr. John Sweetenham: Absolutely. Let's stay on the theme of diffuse large B-cell lymphoma and look at one other abstract in that space, which was Abstract 7000. This was a study from the HOVON group in the Netherlands, which looked at the prospective validation of end-of-treatment circulating tumor DNA in the context of a national randomized trial. What are your thoughts on this? Dr. Marc Braunstein: So, non-invasive liquid biopsies to detect and monitor cancers via circulating tumor-derived DNA or ctDNA, you know, is really emerging as a valuable tool in both solid and liquid tumors to understand disease biology, and also for drug development. So, to date, the most established application of ctDNA in lymphoma, I would say, is really for monitoring of minimal residual disease. So, in this correlative study by Steven Wang and colleagues in the HOVON group, they evaluated the prognostic significance of MRD status as assessed by ctDNA following first-line treatment with curative intent with either R-CHOP or dose-adjusted R-EPOCH. At the end of treatment, encouragingly, 76% of patients were MRD-negative, and 24% were MRD-positive. Now, of note, MRD-positive status at the end of treatment predicted inferior progression-free survival at 2 years, with only 28% of patients who are MRD-positive being progression-free versus 88% who are MRD-negative. And in fact, all the patients who failed to achieve a complete response after first-line treatment and were MRD-positive ultimately relapsed. So, circulating tumor cells are rarely found in large B-cell lymphomas, and so this study really builds on accumulating data that ctDNA has clinical value to detect residual disease with a non-invasive approach. So, there are many implications of how we could potentially use this to detect early signs of relapse, to potentially escalate treatment for consolidation if patients remain MRD-positive. So, I think this will eventually become utilized in clinical practice. Dr. John Sweetenham: Yeah, I agree. I think it's interesting that it provided an independent assessment of response, which was independent, in fact, of the results of PET-CT scanning and so on, which I think was very interesting to me. And the authors of the abstract actually commented in their presentation that they think this should be integrated as part of the standard response assessment now for patients with large B-cell lymphoma. Would you agree with that? Dr. Marc Braunstein: I would. For one thing, it allows repeated sampling. It's a non-invasive approach; it doesn't necessarily require a bone marrow biopsy, and it may have more sensitivity than conventional response measures. So, I think having a standardized system to assess ctDNA will be helpful, and definitely, I think this will be a valuable biomarker of disease response. Dr. John Sweetenham: Okay, great. Thanks. We're going to change gear again now, and we're going to highlight two abstracts in the multiple myeloma space. The first one of these is Abstract 7507. And this abstract reported on the long-term results of the CARTITUDE study for patients with relapsed and refractory multiple myeloma. What are your comments on this presentation? Dr. Marc Braunstein: So, this study actually got a lot of press, and I've already had multiple patients asking me about CAR T-cells as a result. Just as some background, CAR T-cells targeting BCMA, which is pretty much universally expressed on malignant plasma cells in myeloma, have really shown remarkable responses, especially in heavily pretreated patients, showing superior progression-free survival in both later and earlier phases of the disease, including in randomized studies in patients with second-line or beyond. So, the CARTITUDE-1 was really the original Phase 1/2 study of ciltacabtagene autoleucel, one of the two approved anti-BCMA CAR T-cell products, which was investigated in patients with a median of six to seven prior lines of therapy. So, these were patients who were pretty heavily pretreated. So, in the study presented by Voorhees at this year's ASCO meeting, this was the long-term follow-up at a median of 5 years from the one-time CAR infusion in these patients with a median of five prior lines of therapy. And remarkably, of the 97 patients, 33% remained progression-free at 5 years plus, without needing any further myeloma treatment during that time. And among those 33% of patients, 23% had high-risk cytogenetics, which we know are notoriously difficult to achieve responses in. What was interesting that they presented as correlative studies was there were some biomarkers that were distinguishing the patients who had the long PFS, including enrichment of more naive T-cells in the product, lower neutrophil-to-T-cell ratio, higher hemoglobin and platelets at baseline, and higher CAR T-cell levels relative to soluble BCMA levels. And the fact that they reported a median overall survival of 61 months in these really heavily pretreated patients, I think these data are impressive. I think we're going to continue to be using CAR T even earlier in the disease status than fifth or sixth line, as it was studied in CARTITUDE-1. There are even ongoing studies looking at first-line treatment with CAR T-cells. Dr. John Sweetenham: So, do you think that those 33% of patients who are disease-free at 5 years, do you think any of those are cured?  Dr. Marc Braunstein: That was one of the headlines in the press. I think if we're going to discuss things like "operational cures," where we're transforming myeloma into really a chronic disease, where patients can live practically a normal life expectancy, I think the measure of 5 years, especially in this population that was explored in CARTITUDE-1, I think we can call that close to a cure. Dr. John Sweetenham: Okay. Well, thank you. Exciting data, for sure. We're going to conclude today with another abstract in the multiple myeloma space. And this was Abstract 7500, which looked at an MRD, minimal residual disease-driven strategy following induction and transplant-eligible newly diagnosed multiple myeloma patients and reported on the primary endpoints of the phase 3 MIDAS trial. Can you walk us through this one, Marc? Dr. Marc Braunstein: Absolutely. It is a bit more complicated than the prior one we discussed because this is a randomized study with four arms. So, I'll start by saying that anti-CD38-based quadruplet regimens continue to show superior outcomes in both transplant-eligible and -ineligible newly diagnosed multiple myeloma patients. The MIDAS study mentioned is an open-label phase 3 trial with four arms in transplant-eligible newly diagnosed myeloma patients.  And initially, these patients were all treated with quadruplet therapy with the anti-CD38 antibody isatuximab combined with carfilzomib, lenalidomide, and dexamethasone in 718 newly diagnosed myeloma patients. So, they received the quadruplet regimen for six cycles and then were randomized based on their MRD status at 10 to the negative fifth following six cycles of induction. And that first randomization, if they were MRD-negative, was to either consolidation with six more cycles of the quadruplet regimen or transplant, autologous transplant, plus two cycles additionally of the quadruplet regimen. And both arms were followed by lenalidomide maintenance. The primary endpoint was MRD negativity at 10 to the negative sixth prior to entering the lenalidomide maintenance component. And in addition, the patients who were MRD-positive after induction were randomized to transplant plus two cycles of consolidation or a tandem autologous transplant. So, the median follow-up of the study was about 16 months, and the pre-maintenance rate of MRD negativity was high, between 84 to 86% between the two arms who were MRD-negative, which was not significantly different. And as far as the 233 patients who were MRD-positive, the pre-maintenance MRD negativity was also not significantly different at 40% for those who received autologous transplant, and 32% who received a tandem transplant. So, there's a lot of debate in the myeloma field about the evolving role of autologous transplant and whether transplant still plays a significant role in patients who are either MRD-negative after induction or who have deep remissions and are of standard risk. So, I think these data suggest that patients who are MRD-negative after induction with a quadruplet regimen studied here, which was Isa-KRd, plus consolidation, may possibly be able to forego consolidation with autologous transplant. And likewise, for those patients who are MRD-positive after induction, tandem transplant didn't seem to provide much of a benefit compared to single transplant, which is consistent with prior studies such as the StaMINA study. Dr. John Sweetenham: So, where do you think this leaves us, Marc? Are we going to need more studies before we have any definitive guidance on whether an autologous transplant is still appropriate for those patients who are MRD-negative? Dr. Marc Braunstein: Well, as clinicians, we want to do what's best for our patient. And in myeloma, the best we can do is to get as deep remissions as possible, meaning MRD negativity. And so, I think it's clear from the MIDAS study and others that quadruplet regimens provide the deepest remissions when given upfront. We can debate the role of autologous transplant. I think certainly the role of tandem autologous transplant is fading. But as far as a single autologous transplant as consolidation, I think it's reasonable as a goal to try to achieve MRD negativity after the transplant, especially for patients who remain MRD-positive after induction. Dr. John Sweetenham: Okay, great. Marc, thanks as always for sharing your insights on the heme malignancies studies from the ASCO meeting this year and for joining us on the ASCO Daily News Podcast. Always appreciate hearing your thoughtful and balanced input on these. Dr. Marc Braunstein: My pleasure. Thank you, John. Dr. John Sweetenham: And 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 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 guest:  Dr. John Sweetenham Dr. Marc Braunstein   @docbraunstein     Follow ASCO on social media:   @ASCO on Twitter  ASCO on Bluesky  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

Prof Nicolas Girard, Dr Jonathan Goldman, Dr Pasi Jänne, Dr Suresh Ramalingam, Dr Joshua Sabari and moderator Dr Helena Yu present data informing treatment decision-making for EGFR-mutated NSCLC at the 2025 ASCO annual meeting. CME information and select publications here.

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

What does the future of cancer care look like? From replacing IV chemo with oral agents to game-changing advances in bispecific and trispecific therapies, this special bonus episode dives deep into the most exciting—and practice-changing—developments from the 2025 ASCO Annual Meeting.NCODA's Kelly Brunk, PharmD, BCOP, returns from ASCO energized and ready to share his top takeaways in a candid conversation about where oncology is headed. Whether you're a clinician, pharmacist, or anyone in the cancer care ecosystem, this episode is packed with insight you don't want to miss.Bonus: Kelly also shares updates on NCODA's new Immunotherapy Hub and offers a forward-looking take on where the field is headed."The rate of change in oncology care is accelerating—and it's time for practices to be ready, not reactive." — Kelly Brunk Inside the Episode:How oral therapies are reshaping breast cancer treatmentThe evolving role of bispecifics, trispecifics, and antibody-drug conjugatesPractical considerations for implementation: protocols, access, and infrastructureThe importance of quality of life in treatment decisionsEarly use of immune checkpoint inhibitors in multiple disease statesHow AI and equity are shaping the next decade of oncology Listen now and explore what these developments mean for clinical practice—and for the patients at the center of it all. Resources mentioned:NCODA's Immunotherapy Hub – A central resource offering clinical tools, SOP examples, and support for implementing therapies like bispecifics and antibody-drug conjugates.Questions or looking to connect? Email the NCODA Clinical Team at clinical@ncoda.org

An expert panel highlights key presentations in multiplemyeloma, lymphoma, and other hematologic malignancies at the 2025 ASCO Annual Meeting.CancerNetwork®, in collaboration with The American Societyfor Transplantation and Cellular Therapy (ASTCT), organized an X Space hosted by Rahul Banerjee, MD, FACP; Taha Al-Juhaishi, MD; and Muhammad Salman Faisal, MD. This expert panel convened to discuss key presentations and abstracts of interest at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting featuring noteworthy developments in modalities like CAR T-cell therapy and transplantation across multiple myeloma, lymphoma, and other disease types.Banerjee is an assistant professor in the Clinical Research Division at the Fred Hutchinson Cancer Center in Seattle, Washington. Al-Juhaishi is the associate director of the Hematopoietic Stem Cell Transplantation and Cell Therapy Program at Oklahoma University Health Stephenson Cancer Center and an assistant professor of medicine at the University of Oklahoma College of Medicine. Faisal is a hematologist/oncologist at Oklahoma University HealthStephenson Cancer Center and serves as an ambassador for ASCO.The group highlighted several late-breaking abstracts,plenary sessions, and poster presentations focused on significant clinical trial data and other findings across the hematologic oncology landscape. Topics of interest included the following:Phase 1b/2 CARTITUDE-1 trial (NCT03548207,NCT05201781)1Long-term follow-up showed that approximately one-third(33%; n = 32) of patients with relapsed/refractory multiple myeloma maintained progression-free status for at least 5 years following a single infusion of ciltacabtagene autoleucel (cilta-cel; Carvykti). An equal likelihood of progression-free survival occurred in patients with high-risk cytogenetics or extramedullary plasmacytomas.With a median follow-up of 61.3 months, the median overall survival (OS) with cilta-cel was 60.7 months (95% CI, 41.9-notevaluable [NE]). Real-world axicabtagene ciloleucel (axi-cel; Yescarta) use2Across inpatient and outpatient treatment settings, safety and efficacy outcomes were comparable for patients who received axi-cel for relapsed/refractory large B-cell lymphoma.Multivariate analysis showed no associations between intended care setting and cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome.Investigators noted that these real-world data support the consideration of axi-cel in appropriate outpatient settings.Phase 1b/2 NEXICART-2 trial (NCT06097832)3Investigators assessed NXC-201, a sterically optimized CAR T construct, as a treatment for patients with relapsed/refractory light chain amyloidosis, a population with no FDA-approved options.Among 12 patients who received the agent at 450x 106 cells, 100% achieved rapid and deep hematologic responses at a median time to first and best response of 7 and 26 days, respectively. With a median follow-up of 121 days (range, 29-289), no hematologic relapses or progression had occurred.References1.     Voorhees P, Martin T, Lin Y, et al. Long-term (≥5 year) remission and survival after treatment with ciltacabtagene autoleucel (cilta-cel) in CARTITUDE-1 patients (pts) with relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2025;43(suppl 16):7507. doi: 10.1200/JCO.2025.43.16_suppl.75072.     Furqan F, Hemmer M, Tees M, et al. Trends and outcomes by inpatient and outpatient infusion of axicabtagene ciloleucel (axi-cel) in the US for patients (pts) with relapsed/refractory large B-celllymphoma (R/R LBCL). J Clin Oncol. 2025;43(suppl 16):7023. doi:10.1200/JCO.2025.43.16_suppl.70233.     Landau H, Hughes C, Rosenberg A, et al. Safety and efficacy data from Nexicart-2, the first US trial of CAR-T in R/R light chain (AL) amyloidosis, Nxc-201. J Clin Oncol. 2025;43(suppl 16):7508.doi:10.1200/JCO.2025.43.16_suppl.7508

In today's episode, we spoke with Paolo Tarantino, MD, about key updates in HER2-positive breast cancer presented at the 2025 ASCO Annual Meeting

This week's episode will be focusing on exciting data in GU presented at the 2025 ASCO Annual Meeting in prostate (including prognostication of PSA response in mCSPC, AMPLITUDE - PARPi in mCSPC), RCC (including updates in KN-564, CM-214 and PDIGREE), and finally bladder CA (with updates in NIAGARA and EV-302) among others. 

Dr. Nathan Pennell and Dr. Cheryl Czerlanis discuss challenges in lung cancer screening and potential solutions to increase screening rates, including the use of AI to enhance risk prediction and screening processes. Transcript Dr. Nate Pennell: Hello, and welcome to By the Book, a monthly podcast series for ASCO Education that features engaging discussions between editors and authors from the ASCO Educational Book. I'm Dr. Nate Pennell, the co-director of the Cleveland Clinic Lung Cancer Program and vice chair of clinical research for the Taussig Cancer Center. I'm also the editor-in-chief for the ASCO Educational Book.  Lung cancer is one of the leading causes of cancer-related mortality worldwide, and most cases are diagnosed at advanced stages where curative treatment options are limited. On the opposite end, early-stage lung cancers are very curable. If only we could find more patients at that early stage, an approach that has revolutionized survival for other cancer types such as colorectal and breast cancer.  On today's episode, I'm delighted to be joined by Dr. Cheryl Czerlanis, a professor of medicine and thoracic medical oncologist at the University of Wisconsin Carbone Cancer Center, to discuss her article titled, "Broadening the Net: Overcoming Challenges and Embracing Novel Technologies in Lung Cancer Screening." The article was recently published in the ASCO Educational Book and featured in an Education Session at the 2025 ASCO Annual Meeting. Our full disclosures are available in the transcript of this episode.  Cheryl, it's great to have you on the podcast today. Thanks for being here. Dr. Cheryl Czerlanis: Thanks, Nate. It's great to be here with you. Dr. Nate Pennell: So, I'd like to just start by asking you a little bit about the importance of lung cancer screening and what evidence is there that lung cancer screening is beneficial. Dr. Cheryl Czerlanis: Thank you. Lung cancer screening is extremely important because we know that lung cancer survival is closely tied to stage at diagnosis. We have made significant progress in the treatment of lung cancer, especially over the past decade, with the introduction of immunotherapies and targeted therapies based on personalized evaluation of genomic alterations. But the reality is that outside of a lung screening program, most patients with lung cancer present with symptoms related to advanced cancer, where our ability to cure the disease is more limited.  While lung cancer screening has been studied for years, the National Lung Screening Trial, or the NLST, first reported in 2011 a significant reduction in lung cancer deaths through screening. Annual low-dose CT scans were performed in a high-risk population for lung cancer in comparison to chest X-ray. The study population was comprised of asymptomatic persons aged 55 to 74 with a 30-pack-year history of smoking who were either active smokers or had quit within 15 years. The low-dose CT screening was associated with a 20% relative risk reduction in lung cancer-related mortality. A similar magnitude of benefit was also reported in the NELSON trial, which was a large European randomized trial comparing low-dose CT with a control group receiving no screening. Dr. Nate Pennell: So, this led, of course, to approval from CMS (Centers for Medicare and Medicaid Services) for lung cancer screening in the Medicare population, probably about 10 years ago now, I think. And there are now two major trials showing an unequivocal reduction in lung cancer-related mortality and even evidence that it reduces overall mortality with lung cancer screening. But despite this, lung cancer screening rates are very low in the United States. So, first of all, what's going on? Why are we not seeing the kinds of screening rates that we see with mammography and colonoscopy? And what are the barriers to that here? Dr. Cheryl Czerlanis: That's a great question. Thank you, Nate. In the United States, recruitment for lung cancer screening programs has faced numerous challenges, including those related to socioeconomic, cultural, logistical, and even racial disparities. Our current lung cancer screening guidelines are somewhat imprecise and often fail to address differences that we know exist in sex, smoking history, socioeconomic status, and ethnicity. We also see underrepresentation in certain groups, including African Americans and other minorities, and special populations, including individuals with HIV. And even where lung cancer screening is readily available and we have evidence of its efficacy, uptake can be low due to both provider and patient factors. On the provider side, barriers include having insufficient time in a clinic visit for shared decision-making, fear of missed test results, lack of awareness about current guidelines, concerns about cost, potential harms, and evaluating both true and false-positive test results.  And then on the patient side, barriers include concerns about cost, fear of getting a cancer diagnosis, stigma associated with tobacco smoking, and misconceptions about the treatability of lung cancer. Dr. Nate Pennell: I think those last two are really what make lung cancer unique compared to, say, for example, breast cancer, where there really is a public acceptance of the value of mammography and that breast cancer is no one's fault and that it really is embraced as an active way you can take care of yourself by getting your breast cancer screening. Whereas in lung cancer, between the stigma of smoking and the concern that, you know, it's a death sentence, I think we really have some work to be made up, which we'll talk about in a minute about what we can do to help improve this.  Now, that's in the U.S. I think things are probably, I would imagine, even worse when we leave the U.S. and look outside, especially at low- and middle-income countries. Dr. Cheryl Czerlanis: Yes, globally, this issue is even more complex than it is in the United States. Widespread implementation of low-dose CT imaging for lung cancer screening is limited by manpower, infrastructure, and economic constraints. Many low- and middle-income countries even lack sufficient CT machines, trained personnel, and specialized facilities for accurate and timely screenings. Even in urban centers with advanced diagnostic facilities, the high screening and follow-up care costs can limit access. Rural populations face additional barriers, such as geographic inaccessibility of urban centers, transportation costs, language barriers, and mistrust of healthcare systems. In addition, healthcare systems in these regions often prioritize infectious diseases and maternal health, leaving limited room for investments in noncommunicable disease prevention like lung cancer screening. Policymakers often struggle to justify allocating resources to lung cancer screening when immediate healthcare needs remain unmet. Urban-rural disparities exacerbate these challenges, with rural regions frequently lacking the infrastructure and resources to sustain screening programs. Dr. Nate Pennell: Well, it's certainly an intimidating problem to try to reduce these disparities, especially between the U.S. and low- and middle-income countries. So, what are some of the potential solutions, both here in the U.S. and internationally, that we can do to try to increase the rates of lung cancer screening? Dr. Cheryl Czerlanis: The good news is that we can take steps to address these challenges, but a multifaceted approach is needed. Public awareness campaigns focused on the benefits of early detection and dispelling myths about lung cancer screening are essential to improving participation rates. Using risk-prediction models to identify high-risk individuals can increase the efficiency of lung cancer screening programs. Automated follow-up reminders and screening navigators can also ensure timely referrals and reduce delays in diagnosis and treatment. Reducing or subsidizing the cost of low-dose CT scans, especially in low- or middle-income countries, can improve accessibility. Deploying mobile CT scanners can expand access to rural and underserved areas.  On a global scale, integrating lung cancer screening with existing healthcare programs, such as TB or noncommunicable disease initiatives, can enhance resource utilization and program scalability. Implementing lung cancer screening in resource-limited settings requires strategic investment, capacity building, and policy interventions that prioritize equity. Addressing financial constraints, infrastructure gaps, and sociocultural barriers can help overcome existing challenges. By focusing on cost-effective strategies, public awareness, and risk-based eligibility criteria, global efforts can promote equitable access to lung cancer screening and improve outcomes.  Lastly, as part of the medical community, we play an important role in a patient's decision to pursue lung cancer screening. Being up to date with current lung cancer screening recommendations, identifying eligible patients, and encouraging a patient to undergo screening often is the difference-maker. Electronic medical record (EMR) systems and reminders are helpful in this regard, but relationship building and a recommendation from a trusted provider are really essential here. Dr. Nate Pennell: I think that makes a lot of sense. I mean, there are technology improvements. For example, our lung cancer screening program at The Cleveland Clinic, a few years back, we finally started an automated best practice alert in our EMR for patients who met the age and smoking requirements, and it led to a six-fold increase in people referred for screening. But at the same time, there's a difference between just getting this alert and putting in an order for lung cancer screening and actually getting those patients to go and actually do the screening and then follow up on it. And that, of course, requires having that relationship and discussion with the patient so that they trust that you have their best interests. Dr. Cheryl Czerlanis: Exactly. I think that's important. You know, certainly, while technology can aid in bringing patients in, there really is no substitute for trust-building and a personal relationship with a provider. Dr. Nate Pennell: I know that there are probably multiple examples within the U.S. where health systems or programs have put together, I would say, quality improvement projects to try to increase lung cancer screening and working with their community. There's one in particular that you discuss in your paper called the "End Lung Cancer Now" initiative. I wonder if you could take us through that. Dr. Cheryl Czerlanis: Absolutely. "End Lung Cancer Now" is an initiative at the Indiana University Simon Comprehensive Cancer Center that has the vision to end suffering and death from lung cancer in Indiana through education and community empowerment. We discuss this as a paradigm for how community engagement is important in building and scaling a lung cancer screening program.  In 2023, the "End Lung Cancer Now" team decided to focus its efforts on scaling and transforming lung cancer screening rates in Indiana. They developed a task force with 26 experts in various fields, including radiology, pulmonary medicine, thoracic surgery, public health, and advocacy groups. The result of this work is an 85-page blueprint with key recommendations that any system and community can use to scale lung cancer screening efforts. After building strong infrastructure for lung cancer screening at Indiana University, they sought to understand what the priorities, resources, and challenges in their communities were. To do this, they forged strong partnerships with both local and national organizations, including the American Lung Association, American Cancer Society, and others. In the first year, they actually tripled the number of screening low-dose CTs performed in their academic center and saw a 40% increase system-wide. One thing that I think is the most striking is that through their community outreach, they learned that most people prefer to get medical care close to home within their own communities. Establishing a way to support the local infrastructure to provide care became far more important than recruiting patients to their larger system.  In exciting news, "End Lung Cancer Now" has partnered with the IU Simon Comprehensive Cancer Center and IU Health to launch Indiana's first and only mobile lung screening program in March of 2025. This mobile program travels around the state to counties where the highest incidence of lung cancer exists and there is limited access to screening. The mobile unit parks at trusted sites within communities and works in partnership, not competition, with local health clinics and facilities to screen high-risk populations. Dr. Nate Pennell: I think that sounds like a great idea. Screening is such an important thing that it doesn't necessarily have to be owned by any one particular health system for their patients. I think. And I love the idea of bringing the screening to patients where they are. I can speak to working in a regional healthcare system with a main campus in the downtown that patients absolutely hate having to come here from even 30 or 40 minutes away, and they'd much rather get their care locally. So that makes perfect sense.  So, under the current guidelines, there are certainly things that we can do to try to improve capturing the people that meet those. But are those guidelines actually capturing enough patients with lung cancer to make a difference? There certainly are proposals within patient advocacy communities and even other countries where there's a large percentage of non-smokers who perhaps get lung cancer. Can we expand beyond just older, current and heavy smokers to identify at-risk populations who could benefit from screening? Dr. Cheryl Czerlanis: Yes, I think we can, and it's certainly an active area of research interest. We know that tobacco is the leading cause of lung cancer worldwide. However, other risk factors include secondhand smoke, family history, exposure to environmental carcinogens, and pulmonary diseases like COPD and interstitial lung disease. Despite these known associations, the benefit of lung cancer screening is less well elucidated in never-smokers and those at risk of developing lung cancer because of family history or other risk factors. We know that the eligibility criteria associated with our current screening guidelines focus on age and smoking history and may miss more than 50% of lung cancers. Globally, 10% to 25% of lung cancer cases occur in never-smokers. And in certain parts of the world, like you mentioned, Nate, such as East Asia, many lung cancers are diagnosed in never-smokers, especially in women. Risk-prediction models use specific risk factors for lung cancer to enhance individual selection for screening, although they have historically focused on current or former smokers.  We know that individuals with family members affected by lung cancer have an increased risk of developing the disease. To this end, several large-scale, single-arm prospective studies in Asia have evaluated broadening screening criteria to never-smokers, with or without additional risk factors. One such study, the Taiwan Lung Cancer Screening in Never-Smoker Trial, was a multicenter prospective cohort study at 17 medical centers in Taiwan. The primary outcome of the TALENT trial was lung cancer detection rate. Eligible patients aged 55 to 75 had either never smoked or had a light and remote smoking history. In addition, inclusion required one or more of the following risk factors: family history of lung cancer, passive smoke exposure, history of TB or COPD, a high cooking index, which is a metric that quantifies exposure to cooking fumes, or a history of cooking without ventilation. Participants underwent low-dose CT screening at baseline, then annually for 2 years, and then every 2 years for up to 6 years. The lung cancer detection rate was 2.6%, which was higher than that reported in the NLST and NELSON trials, and most were stage 0 or I cancers. Subsequently, this led to the Taiwan Early Detection Program for Lung Cancer, a national screening program that was launched in 2022, targeting 2 screening populations: individuals with a heavy history of smoking and individuals with a family history of lung cancer.  We really need randomized controlled trials to determine the true rates of overdiagnosis or finding cancers that would not lead to morbidity or mortality in persons who are diagnosed, and to establish whether the high lung detection rates are associated with a decrease in lung cancer-related mortality in these populations. However, the implementation of randomized controlled low-dose CT screening trials in never-smokers has been limited by the need for large sample sizes, lengthy follow-up, and cost.  In another group potentially at higher risk for developing lung cancer, the role of lung cancer screening in individuals who harbor germline pathogenic variants associated with lung cancer also needs to be explored further. Dr. Nate Pennell: We had this discussion when the first criteria came out because there have always been risk-based calculators for lung cancer that certainly incorporate smoking but other factors as well and have discussion about whether we should be screening people based on their risk and not just based on discrete criteria such as smoking. But of course, the insurance coverage for screening, you have to fit the actual criteria, which is very constrained by age and smoking history. Do you think in the U.S. there's hope for broadening our screening beyond NLST and NELSON criteria? Dr. Cheryl Czerlanis: I do think at some point there is hope for broadening the criteria beyond smoking history and age, beyond the criteria that we have typically used and that is covered by insurance. I do think it will take some work to perhaps make the prediction models more precise or to really understand who can benefit. We certainly know that there are many patients who develop lung cancer without a history of smoking or without family history, and it would be great if we could diagnose more patients with lung cancer at an earlier stage. I think this will really count on there being some work towards trying to figure out what would be the best population for screening, what risk factors to look for, perhaps using some new technologies that may help us to predict who is at risk for developing lung cancer, and trying to increase the group that we study to try and find these early-stage lung cancers that can be cured. Dr. Nate Pennell: Part of the reason we, of course, try to enrich our population is screening works better when you have a higher pretest probability of actually having cancer. And part of that also is that our technology is not that great. You know, even in high-risk patients who have CT scans that are positive for a screen, we know that the vast majority of those patients with lung nodules actually don't have lung cancer. And so you have to follow them, you have to use various models to see, you know, what the risk, even in the setting of a positive screen, is of having lung cancer.  So, why don't we talk about some newer tools that we might use to help improve lung cancer screening? And one of the things that everyone is super excited about, of course, is artificial intelligence. Are there AI technologies that are helping out in early detection in lung cancer screening? Dr. Cheryl Czerlanis: Yes, that's a great question. We know that predicting who's at risk for lung cancer is challenging for the reasons that we talked about, knowing that there are many risk factors beyond smoking and age that are hard to quantify. Artificial intelligence is a tool that can help refine screening criteria and really expand screening access. Machine learning is a form of AI technology that is adept at recognizing patterns in large datasets and then applying the learning to new datasets. Several machine learning models have been developed for risk stratification and early detection of lung cancer on imaging, both with and without blood-based biomarkers. This type of technology is very promising and can serve as a tool that helps to select individuals for screening by predicting who is likely to develop lung cancer in the future.  A group at Massachusetts General Hospital, represented in our group for this paper by my co-authors, Drs. Fintelmann and Chang, developed Sybil, which is an open-access 3D convolutional neural network that predicts an individual's future risk of lung cancer based on the analysis of a single low-dose CT without the need for human annotation or other clinical inputs. Sybil and other machine learning models have tremendous potential for precision lung cancer screening, even, and perhaps especially, in settings where expert image interpretation is unavailable. They could support risk-adapted screening schedules, such as varying the frequency and interval of low-dose CT scans according to individual risk and potentially expand lung cancer screening eligibility beyond age and smoking history. Their group predicts that AI tools like Sybil will play a major role in decoding the complex landscape of lung cancer risk factors, enabling us to extend life-saving lung cancer screening to all who are at risk. Dr. Nate Pennell: I think that that would certainly be welcome. And as AI is working its way into pretty much every aspect of life, including medical care, I think it's certainly promising that it can improve on our existing technology.  We don't have to spend a lot of time on this because I know it's a little out of scope for what you covered in your paper, but I'm sure our listeners are curious about your thoughts on the use of other types of testing beyond CT screening for detecting lung cancer. I know that there are a number of investigational and even commercially available blood tests, for example, for detection of lung cancer, or even the so-called multi-cancer detection blood tests that are now being offered, although not necessarily being covered by insurance, for multiple types of cancer, but lung cancer being a common cancer is included in that. So, what do you think? Dr. Cheryl Czerlanis: Yes, like you mentioned, there are novel bioassays such as blood-based biomarker testing that evaluate for DNA, RNA, and circulating tumor cells that are both promising and under active investigation for lung cancer and multi-cancer detection. We know that such biomarker assays may be useful in both identifying lung cancers but also in identifying patients with a high-risk result who should undergo lung cancer screening by conventional methods. Dr. Nate Pennell: Anything that will improve on our rate of screening, I think, will be welcome. I think probably in the future, it will be some combination of better risk prediction and better interpretation of screening results, whether those be imaging or some combination of imaging and biomarkers, breath-based, blood-based. There's so much going on that it is pretty exciting, but we're still going to have to overcome the stigma and lack of public support for lung cancer screening if we're going to move the needle. Dr. Cheryl Czerlanis: Yes, I think moving the needle is so important because we know lung cancer is still a very morbid disease, and our ability to cure patients is not where we would like it to be. But I do believe there's hope. There are a lot of motivated individuals and groups who are passionate about lung cancer screening, like myself and my co-authors, and we're just happy to be able to share some ways that we can overcome the challenges and really try and make an impact in the lives of our patients. Dr. Nate Pennell: Well, thank you, Dr. Czerlanis, for joining me on the By the Book Podcast today and for all of your work to advance care for patients with lung cancer. Dr. Cheryl Czerlanis: Thank you, Dr. Pennell. It's such a pleasure to be with you today. Thank you. Dr. Nate Pennell: And thank you to our listeners for joining us today. You'll find a link to Dr. Czerlanis' article in the transcript of this episode.  Please join us again next month for By the Book's next episode and more insightful views on topics you'll be hearing at the education sessions from ASCO meetings throughout the year, and our deep dives on approaches that are shaping modern oncology. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers:     Dr. Nathan Pennell    @n8pennell   @n8pennell.bsky.social Dr. Cheryl Czerlanis Follow ASCO on social media:     @ASCO on X (formerly Twitter)     ASCO on Bluesky    ASCO on Facebook     ASCO on LinkedIn     Disclosures:    Dr. Nate 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 (Institution): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi    Dr. Cheryl Czerlanis: Research Funding (Institution): LungLife AI, AstraZeneca, Summit Therapeutics

2025 ASCO Annual Meeting Highlights with guest Dr. Ian Krop June 8, 2025 Yale Cancer Center visit: http://www.yalecancercenter.org email: canceranswers@yale.edu call: 203-785-4095

Concluding their three-episode series filmed live in Chicago, your hosts wrap up the weekend with a discussion of the key bladder cancer presentations from the 2025 ASCO Annual Meeting. They begin in the perioperative space, reviewing updated CREST data presented since AUA and revisiting the NIAGARA trial last seen at ESMO 2024, and end by covering the latest EV-302 updates in the metastatic setting.The View on GU with Lalani & Wallis integrates key clinical data from major conferences and high impact publications, sharing meaningful take home messages for practising clinicians in the field of genitourinary (GU) cancers. Learn more about The View on GU: theviewongu.caThis podcast has been made possible through unrestricted financial support by Novartis, Bayer, Astellas, Tolmar, Ipsen, J&J, Merck, Pfizer, Eisai and AbbVie.

In deze podcast bespreekt Koos van der Hoeven met Inge Baas, werkzaam in het UMC Utrecht, de laatste ontwikkelingen met betrekking tot de behandeling van gynaecologische tumoren gepresenteerd tijdens de 2025 ASCO Annual Meeting.

In deze podcast bespreekt Koos van der Hoeven met Astrid van der Veldt, werkzaam in het Erasmus MC te Rotterdam, de laatste ontwikkelingen met betrekking tot de behandeling van melanoom gepresenteerd tijdens de 2025 ASCO Annual Meeting.

In deze podcast bespreekt Koos van der Hoeven met Hanneke van Laarhoven, werkzaam in het Amsterdam UMC, de laatste ontwikkelingen met betrekking tot de behandeling van upper GI-tumoren gepresenteerd tijdens de 2025 ASCO Annual Meeting.

In deze podcast bespreekt Koos van der Hoeven met Jeanine Roodhart, werkzaam in het UMC Utrecht, de laatste ontwikkelingen met betrekking tot de behandeling van coloncarcinomen gepresenteerd tijdens de 2025 ASCO Annual Meeting.

Picking up from Episode 23, your hosts turn their focus to the highly anticipated prostate cancer presentations from the 2025 ASCO Annual Meeting in Chicago. They begin with a discussion on mCSPC, focusing on the AMPLITUDE trial, followed by results from TALAPRO-2, the ARANOTE trial, IRONMAN, and STAMPEDE. The episode wraps with key abstracts and oral presentations on mCRPC.The View on GU with Lalani & Wallis integrates key clinical data from major conferences and high impact publications, sharing meaningful take home messages for practising clinicians in the field of genitourinary (GU) cancers. Learn more about The View on GU: theviewongu.caThis podcast has been made possible through unrestricted financial support by Novartis, Bayer, Astellas, Tolmar, Ipsen, J&J, Merck, Pfizer, Eisai and AbbVie.

Recorded live in Chicago, your hosts explore the latest in kidney cancer, discussing new five-year follow-up data from KEYNOTE-564, the long-term results of CheckMate 214, insights from the ongoing PDIGREE trial, and much more.The View on GU with Lalani & Wallis integrates key clinical data from major conferences and high impact publications, sharing meaningful take home messages for practising clinicians in the field of genitourinary (GU) cancers. Learn more about The View on GU: theviewongu.caThis podcast has been made possible through unrestricted financial support by Novartis, Bayer, Astellas, Tolmar, Ipsen, J&J, Merck, Pfizer, Eisai and AbbVie.

In deze podcast bespreekt Koos van der Hoeven met Britt Suelmann, werkzaam in het UMC Utrecht, de laatste ontwikkelingen met betrekking tot de behandeling van blaas- en niercelcarcinomen gepresenteerd tijdens de 2025 ASCO Annual Meeting.

In deze podcast bespreekt Koos van der Hoeven met Joop de Langen, werkzaam in het Antoni van Leeuwenhoek te Amsterdam, de laatste ontwikkelingen met betrekking tot de behandeling van longcarcinomen gepresenteerd tijdens de 2025 ASCO Annual Meeting.

In deze podcast bespreekt Koos van der Hoeven met André Bergman, werkzaam in het Antoni van Leeuwenhoek te Amsterdam, de laatste ontwikkelingen met betrekking tot de behandeling van het prostaatcarcinoom gepresenteerd tijdens de 2025 ASCO Annual Meeting.

In deze podcast bespreekt Koos van der Hoeven met Agnes Jager, werkzaam in het Erasmus MC te Rotterdam, de laatste ontwikkelingen met betrekking tot de behandeling van het mammacarcinoom gepresenteerd tijdens de 2025 ASCO Annual Meeting.

Dr. John Sweetenham shares highlights from Day 5 of the 2025 ASCO Annual Meeting, including data from large trials in advanced malignant melanoma and mCSPC plus a new approach to first-line treatment for patients with multiple myeloma who are not transplant eligible. Transcript Hello, I'm Dr. John Sweetenham, the host of the ASCO Daily News Podcast, with my takeaways on selected abstracts from Day 5 of the 2025 ASCO Annual Meeting. My disclosures are available in the transcript of this episode. The selected abstracts from this final day of ASCO25 include important new data from large, randomized trials in patients with advanced malignant melanoma and patients with metastatic castration-sensitive prostate cancer, as well as a new approach to the first-line treatment of patients with multiple myeloma who are not transplant eligible.  Starting with LBA9500, this study was conducted in patients with completely resected stage III or IV malignant melanoma and compared the combination of relatlimab plus nivolumab versus nivolumab alone in this population. The study, named the RELATIVITY-098 trial, was presented by Dr. Georgina Long from the University of Sydney, Australia. In her introduction to the study, Dr. Long explained that the current standard of care for adjuvant therapy of resected stage III/IV melanoma is with PD-1 monotherapy with nivolumab, but that about 50% of patients will suffer from a subsequent relapse. In the first-line setting in patients with advanced or unresectable melanoma, the combination of nivolumab with the LAG-3 inhibitor, relatlimab, has been previously shown to improve progression-free survival in the RELATIVITY-047 trial. The current study evaluated this same combination in the adjuvant setting. More than 1,000 patients from 24 countries were randomized to receive either nivolumab alone (546 patients) or the combination of nivolumab with relatlimab (547 patients). Both treatments were given for a maximum of 1 year or until progression of disease, unacceptable toxicity, withdrawal, or death. Various biomarker studies were also undertaken including LAG-3 and PD-1 expression on CD8-positive T cells. The primary endpoint of the study was relapse-free survival, and Dr. Long reported that this was the same in both arms of the study. For example, at 24 months, the relapse-free survival was 64% in the monotherapy arm compared with 62% in the combination arm. The hazard ratio was 1.01 and the P value was 0.928. Metastasis-free survival was also identical in both arms. No benefit was observed for the combination in any of the prespecified subgroups. No new toxicity signals emerged compared with the RELATIVITY-047 trial. Interestingly, the baseline surface expression of LAG-3 and co-expression of LAG-3 and PD-1 on CD8 T cells in the 098 adjuvant trial were lower than in the 047 advanced disease trial, perhaps explaining why the combination did not confer benefit over nivo alone in the adjuvant setting. This is an important result, demonstrating that results from one clinical setting cannot always be extrapolated to another. Although the combination has gained some use in the adjuvant setting, this study clearly demonstrates that more drug in this situation is no better and that monotherapy remains the current standard of care. Results from the AMPLITUDE trial for patients with metastatic castration-sensitive prostate cancer with alterations in homologous recombination repair (HRR) genes, in LBA5006, were presented today by Dr. Gerhardt Attard from University College London, UK. This international, multicenter study evaluated the combination of the selective PARP inhibitor, niraparib, in combination with abiraterone acetate and prednisone. The same combination has been previously shown to improve outcomes in castration-resistant metastatic prostate cancer harboring BRCA mutations in the MAGNITUDE study. The current trial included patients with castration-sensitive disease with HRR mutations including BRCA1/2. Six hundred and ninety-six patients were randomized between niraparib, abiraterone, and prednisone plus androgen deprivation therapy, or the same combination with placebo instead of niraparib. Permitted prior therapies included no more than 6 months of prior androgen deprivation therapy and the use of docetaxel, or prior palliative radiation therapy. The primary endpoint of the study was radiographic relapse-free survival. Dr. Attard reported that the risk for radiographic progression-free survival in the whole population was significantly reduced by 37% with niraparib and abiraterone acetate plus prednisone compared with the placebo arm. The radiographic progression-free survival risk reduction with niraparib in the prespecified BRCA1/2 subgroup was 48% and reached statistical significance compared with the placebo arm. The secondary endpoint of time to symptomatic progression was also improved with niraparib in the HRR population and the BRCA1/2 subgroup. There was a trend for overall survival favoring the niraparib combination. However, the overall survival data were immature at this first interim analysis and did not yet reach statistical significance. No new safety concerns emerged with the toxicity data consistent with the MAGNITUDE study. Less than 5% more of the patients on the experimental arm discontinued treatment in comparison to the control arm. The authors conclude that the AMPLITUDE study results support the use of niraparib, abiraterone, and prednisone as a new treatment option for patients with metastatic castration- sensitive prostate cancer and BRCA and homologous recombination repair gene alterations. The results certainly support this conclusion and are potentially practice-changing. Turning to hematologic malignancies, my final selection from today's presentations is Abstract 7504, presented by Dr. Hang Quach from St Vincent's Hospital, Melbourne, Australia, and describes a novel combination of elranatamab, daratumumab, and lenalidomide in patients with newly diagnosed multiple myeloma who are not transplant-eligible – the so-called MagnetisMM-6 trial part 1. Elranatamab is a novel bispecific T-cell engaging antibody directed against BCMA and CD3, which has previously been approved for certain patients with relapsed and refractory multiple myeloma. In the present study, this was combined with lenalidomide and daratumumab in newly diagnosed patients. The report today describes the dose-finding phase of this study, which was part 1, specifically addressing so-called dose level ‘G', comprising elranatamab 76mg subcutaneously every 4 weeks plus daratumumab 1800mg subcutaneously and lenalidomide 25mg given orally. Thirty-seven patients were entered at this dose level, of whom 32 were on treatment at the time of analysis. Early response data show an overall response rate of 97.3%. With median follow up of 7.9 months, the current CR rate is 27% with a VGPR rate of almost 68%. The most frequent toxicities were hematologic, with neutropenia observed in 75%. Some cytokine release syndrome was observed in about 60% of patients, but none was greater than grade 2. The authors conclude that this combination is active in untreated multiple myeloma, with manageable toxicity and evidence of responses which appear to deepen over time. The dose-finding component of this trial is continuing and will subsequently progress into a phase 3 trial based on the data from the current study. This will compare daratumumab plus lenalidomide with the same combination plus elranatamab in previously untreated patients. That concludes our special coverage from the 2025 ASCO Annual Meeting. Thanks for listening and we hope you have enjoyed listening to our top takeaways from ASCO25. If you value the insights that you hear on the ASCO Daily News Podcast, please remember to rate, review, and subscribe wherever you get your podcasts. Disclaimer:  The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  Find out more about today's speaker:    Dr. John Sweetenham    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. John Sweetenham shares highlights from Day 4 of the 2025 ASCO Annual Meeting, including new research on maintenance therapy in small cell lung cancer and a virtual reality psychosocial intervention for patients undergoing hematopoietic stem cell transplantation. Transcript Hello, I'm Dr. John Sweetenham, the host of the ASCO Daily News Podcast, with my takeaways on selected abstracts from Day 4 of the 2025 ASCO Annual Meeting. My disclosures are available in the transcript of this episode. Today's selection features reports of 3 randomized trials in very different clinical settings: maintenance therapy in extensive small cell lung cancer (SCLC), upfront surgery in advanced ovarian cancer, and a supportive care intervention for patients undergoing hematopoietic stem cell transplantation. The first of these studies, Abstract 8006, was presented by Dr. Luis Paz-Ares from the University Hospital [October 12] in Madrid, Spain, and reports the primary results of the IMforte trial. This was a phase 3 trial evaluating the combination of lurbinectedin and atezolizumab as first-line maintenance therapy in patients with extensive small cell lung cancer. Despite some improvements in the first-line treatment of extensive small cell lung cancer with the use of checkpoint inhibitors in combination with platinum-based chemotherapy, most of the patients experience early disease progression and long-term survival remains very limited. This provides a rationale for considering a maintenance intervention. Lurbinectedin is an alkylating agent and transcription inhibitor [that is] already approved in the United States for patients with relapsed/refractory metastatic SCLC following platinum-based chemotherapy. It has been shown to synergize with immune checkpoint inhibitors in pre-clinical studies and has also been evaluated in early-phase clinical trials. The IMforte trial is a global, randomized trial in which patients are initially treated with atezolizumab, and those patients who do not progress on induction therapy are then randomized to maintenance therapy with atezolizumab alone or atezolizumab with lurbinectedin. The primary endpoints of the study were progression-free and overall survival. Four hundred and eighty-three patients were randomized and at a median follow-up of 15 months, the median progression-free survival for patients who received the combination was 5.4 months and the median overall survival was 13.2 months. This compares with 2.1 and 10.6 months, respectively, in patients who received atezolizumab only. The lurbinectedin and atezolizumab combination was generally well-tolerated, with no new or unexpected safety signals. The benefit was consistent in magnitude across all the relevant patient subgroups. This is the first phase 3 study to show a progression-free and overall survivial improvement with first-line maintenance in extensive stage SCLC and the result is likely to be practice-changing, establishing a new standard of care in this tough-to-treat disease. Next up is LBA5500, presented by Dr. Sven Mahner from LMU University in Munich, Germany. This describes the results of the TRUST study, a randomized trial of upfront surgical therapy in advanced ovarian cancer. As background, total macroscopic tumor resection with maximal effort cytoreductive surgery is the cornerstone of treatment in patients with advanced ovarian cancer. The optimal timing of such surgery remains controversial, whether it's more beneficial as a primary cytoreductive surgery before chemotherapy or in the form of interval cytoreductive surgery after 3 cycles of neoadjuvant chemotherapy. Previous studies have addressed this issue, but results have been confounded by issues of patient and center selection. The TRUST study is a randomized, international, multicenter phase 3 trial that compares the outcomes of the timing of surgery in surgically fit patients with seemingly resectable FIGO stage IIIB/IVB ovarian, tubal, and peritoneal carcinoma. To ensure consistent and adequate surgical quality, participating centers in the trial were required to obtain accreditation and undergo an onsite quality assurance review. This included assessment of infrastructure, surgical proficiency, complete resection rates, and surgical volume. Seven hundred and ninety-seven patients with advanced ovarian cancer were randomized to undergo surgery prior to therapy with 6 cycles of carboplatin and paclitaxel along with bevacizumab and a PARP inhibitor, or to have the surgery between the third and fourth cycle of the same systemic therapy. Of the initial 797 patients, 688 comprised the intent-to-treat population, of whom 345 received primary cytoreductive surgery and 343 received neoadjuvant chemotherapy followed by interval cytoreductive surgery.  The results show that patients undergoing primary surgery had significantly improved progression-free survival compared with those who had interval cytoreductive surgery (median progression-free survival was 22.1 months versus 19.7 months). No difference in overall survival was observed between the 2 arms of the study.  This is the first study to show a benefit for primary cytoreductive surgery, although the progression-free survival improvement was not reflected in an overall survival difference. A subgroup analysis for patients who underwent complete cytoreduction suggests a progression-free survival and survival benefit, although it isn't clear to me that the study was powered for this endpoint. Nevertheless, these are very difficult studies to perform, and the investigators should be congratulated for this robustly conducted clinical trial. Today's final abstract is 1504, presented by Dr. Hermioni Amonoo from Harvard Medical School. The trial evaluated BMT-VR, a virtual reality psychosocial intervention for patients undergoing bone marrow transplantation. This randomized trial included adult patients undergoing autologous and allogeneic transplantation. The BMT-VR platform included, among others, modules addressing psychoeducation, coping, acceptance, and gratitude. BMT-VR patients were provided with VR headsets and completed all modules during their hospitalization. Patient-reported outcomes were then assessed at 2, 4, 12, and 24 weeks post-BMT. Use of the VR tool was tracked during hospitalization. Control patients received usual care during their hospital stay and were then assessed at the same intervals post-BMT.  Eighty evaluable patients were randomized, 39 to BMT-VR and 41 to usual care. Completion rates for the BMT-VR modules were high [at] around 70-75%.  Patients who received the BMT-VR intervention experienced significantly improved anxiety, quality of life, and coping at 4 weeks post-BMT. In the longer term, sustained benefits were seen at 24 weeks for some endpoints including quality of life, with some benefits, including for depression and PTSD symptoms, improving longitudinally over the study period. These data are preliminary and will need to be confirmed in larger multicenter studies, but this trial demonstrates the feasibility of using virtual interventions in our patients and also provides intriguing preliminary data that they may be effective. Thanks for listening to today's report and I hope you will join me again tomorrow to hear more top takeaways from the final day of ASCO25. If you value the insights that you hear on the ASCO Daily News Podcast, please remember to rate, review, and subscribe wherever you get your podcasts.   Disclaimer:   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.     Find out more about today's speaker:     Dr. John Sweetenham       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 

JCO Editorial Fellow Dr. Ece Cali Daylan and JCO Associate Editor Dr. Thomas Stinchcombe discuss the ASCO 2025 Simultaneous Publication paper "Neoadjuvant Osimertinib for Resectable EGFR-Mutated Non-Small-Cell Lung Cancer." Transcript The guest on this podcast episode has no disclosures to declare. Dr. Ece Cali: Hello, and welcome to our 2025 ASCO Annual Meeting series, where we cover some of the top JCO papers published simultaneously with their abstract presentation at this year's meeting. I'm your host, Dr. Ece Cali, JCO Editorial Fellow, and I am joined by JCO Associate Editor, Dr. Tom Stinchcombe. In this episode, we will discuss the Journal of Clinical Oncology article and abstract presentation "Neoadjuvant Osimertinib for Resectable EGFR-Mutated Non–Small-Cell Lung Cancer.” NeoADAURA is a randomized global phase III study investigating the efficacy of neoadjuvant osimertinib-containing regimens in patients with resectable EGFR-mutated stage II to IIIB non–small-cell lung cancer. 358 patients were randomized 1:1:1 to receive osimertinib plus chemotherapy, osimertinib monotherapy, or placebo plus chemotherapy in the neoadjuvant setting. The primary endpoint was major pathological response. Osimertinib plus chemotherapy and osimertinib alone demonstrated MPR rates of 26% and 25%, respectively, compared to 2% in the chemotherapy plus placebo arm with a p-value of less than 0.001. Tom, can you please explain to our listeners how you interpret this data? Dr. Thomas Stinchcombe: Great question. Yeah, I think to give a little context, obviously, chemotherapy and immunotherapies preoperatively is becoming the standard of care. However, patients with EGFR-mutant lung cancer generally have not responded to immunotherapy, and many of the trials excluded patients with known EGFR mutation. There have been smaller phase II trials that had looked at EGFR TKIs preoperatively, but none of these were definitive. So I think that this trial is a big trial, and I think some of the strengths are that it has osimertinib alone and chemotherapy with osimertinib arms as compared to the standard of chemotherapy. I think it's going to be really interesting at the meeting to see how this is discussed by the discussant and also what the reaction is to its public presentation. And I think that's largely because there's an alternative paradigm now, surgical resection adjuvant osimertinib, that's available to patients. So I think this will be interesting to see what the reaction is to the induction therapy. For patients with known N2 disease, I've generally given some form of induction therapy prior to surgical resection. So I think that's the subgroup of patients that I'm most likely to employ this approach with based on the results. Dr. Ece Cali: So, in this trial, more than 90% of the patients on the osimertinib-containing regimens underwent curative-intent surgery. So, this speaks to the feasibility of the approach, and the higher MPR rate with osimertinib-containing regimens is encouraging. Event-free survival data is currently immature. You have already touched upon some of the strengths of the trial, but what are the weaknesses and the strengths of this trial? Dr. Thomas Stinchcombe: So, I mean, I think there are some weaknesses. A major pathological response was chosen as an endpoint, and there could be an argument that path CR is more of a prognostic marker. However, the rates of path CR are relatively low, so it would have been very hard to design a trial such as that. And then I think the trial started off as a preoperative trial but effectively became a perioperative trial with preoperative EGFR-TKI, postoperative osimertinib. And so I think it's going to be very hard to determine what the contribution of the components are. And then you've hit on another part that I think is very important when we interpret the data that the maturity on the event-free survival is only 15%, and most people are still on therapy. So the event-free survival, which is an important endpoint, is very immature right now. Dr. Ece Cali: And this trial was designed to compare the neoadjuvant approaches, hence the comparator arm here is neoadjuvant chemotherapy followed by surgery. So, considering the ADAURA trial results with upfront surgery followed by osimertinib as adjuvant, so how do you see this trial's impact on the current clinical practice? Dr. Thomas Stinchcombe: Well, very good question, I think one that we're still struggling with as we kind of look at this data. I think, for me, stage II patients will most likely go to surgery and then get adjuvant osimertinib, and then maybe the N2 patients will get an osimertinib-containing regimen as an induction therapy. I think one of the questions is does it really matter when you get the osimertinib as long as you get it at some point? And I think that's going to be the critical interpretation of some of the data at this point. Dr. Ece Cali: And how do you think this trial shapes the future research for patients with resectable EGFR-mutated lung cancer? Dr. Thomas Stinchcombe: Well, I mean, I think it shows that chemotherapy was really modestly active with an MPR rate of 2%, no pathological responses. And then I think you're going to have to look at an osimertinib plus another targeted therapy component. I think, you know, when I looked at the osimertinib versus the chemo-osimertinib arm, I also was sort of surprised that the MPR rate and the path CR rate were very, very similar. So I think that the question is would a double targeted therapy approach or some other approach matter? And I think it also sets a safety standard. And you touched on this in your comments, that there was not a disparity in terms of the rate of going to surgery or R0/R1 resections. So patients were not having progressive disease events or toxicities that prevented surgery. So I think it does give us good safety data. Dr. Ece Cali: Tom, thank you so much for sharing your insights on the JCO article, "Neoadjuvant Osimertinib for Resectable EGFR-Mutated Non–Small-Cell Lung Cancer." Join us again for the latest simultaneous publications from the 2025 ASCO Annual Meeting, and please take a moment to rate, review, and subscribe to all ASCO podcast shows at asco.org/podcasts. Until then, enjoy the rest of ASCO 2025. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Dr. John Sweetenham shares highlights from Day 3 of the 2025 ASCO Annual Meeting, including new research for the treatment of advanced renal cell carcinoma and 2 studies on novel approaches in non-small cell lung cancer. Transcript Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham, the host of the ASCO Daily News Podcast, with my takeaways on selected abstracts from Day 3 of the 2025 ASCO Annual Meeting. Today's selection features studies addressing the treatment of advanced renal cell carcinoma and 2 studies exploring novel approaches in non-small cell lung cancer. My disclosures are available in the transcript of this episode. The first abstract is number 4505. This study, led by Dr. Toni Choueiri of the Dana-Farber Cancer Institute, describes the final analysis of the CheckMate 214 trial, which compared the combination of nivolumab and ipilimumab with sunitinib for the first-line treatment of advanced renal cell carcinoma. The ipi-nivo combination is approved for the frontline treatment of intermediate and poor-risk advanced renal cell carcinoma based on the primary analysis of the CheckMate 214 trial, which demonstrated a higher response rate and longer overall survival compared with sunitinib. Today's presentation provided the final safety and efficacy results for the trial with long-term follow-up of more than 9 years.  The intent-to-treat (ITT) population in this trial comprised 550 patients randomized to nivo and ipi versus 546 who received sunitinib. The final analysis showed sustained long-term benefit for the combination therapy. Patients given nivolumab plus ipi had a 29% reduction in the risk for death compared with sunitinib. For patients with intermediate or poor-risk disease, there was a 31% reduction in the risk of death.   The probability of remaining in response through 8 years was more than doubled with nivolumab plus ipilimumab versus sunitinib in the ITT population at 48% versus 19%, and in the intermediate and poor-risk population at 50% versus 23%. The other important observation is that patients with favorable-risk disease appeared to have a 20% reduction in the risk for death at 9 years and more durable responses. This suggests a possible delayed benefit for ipi and nivo in this group since these differences were not seen in the earlier analysis.   No new safety signals emerged with longer follow-up, and the results confirm the use of ipi and nivo as a standard front-line combination therapy in this disease. Since this combination has been in widespread use for some years, the results are not surprising although the subgroup analysis suggesting benefit in favorable-risk patients is likely to inform practice in the future.   Today's second abstract is number is 8506, which was presented by Dr. Tony Mok from the Chinese University of Hong Kong, describing results from the phase 3 HERTHENA-Lung02 trial. This trial compared the antibody-drug conjugate patritumab deruxtecan with platinum-based chemotherapy in patients with EGFR-mutated advanced non-small cell lung cancer following a third-generation tyrosine kinase inhibitor (TKI).  Patritumab deruxtecan, also known as HER3-DXd, comprises a fully human anti-HER3 IgG3 monoclonal antibody conjugated to a topoisomerase 1 inhibitor payload, and showed activity in a previous phase 2 trial in patients relapsing after EGFR TKI and chemotherapy.   In this phase 3 study, this agent was compared with platinum-based chemotherapy in eligible patients with an EGFR-activating mutation who had previously received 1 or 2 EGFR TKIs, at least one of which was a third-generation drug, with relapse or progression after this therapy. Five hundred and eighty-six patients were enrolled, with progression-free survival as the primary endpoint.  The primary analysis showed a 9-month progression-free survival of 29% for the experimental arm compared with 19% for platinum-based chemotherapy, for a hazard ratio of 0.77 and a P value of 0.011. With higher progression-free survival rates at 6 months and 12 months, HER3-DXd also had a better objective response rate (35.2% versus 25.3%) compared with platinum-based chemotherapy (PBC), and HER3-DXd also extended intracranial progression-free survival compared with PBC in patients with brain metastases, with a hazard ratio of 0.75. Grade 3 or more treatment-related adverse events occurred in 73% of patients treated with HER3-DXd and 57% of patients who received PBC. HER3-DXd had a higher rate of grade or more 3 thrombocytopenia, and drug-related interstitial lung disease occurred in 5% of patients in the HER3-DXd arm.   The follow-up will need more time to mature since no overall survival data are currently available, but definitely an agent to watch with interest. Moving on to today's final abstract, 8500, was presented by Dr. Pasi Jänne from the Dana-Farber Cancer Institute, describing results from the phase 2 portion of the KRYSTAL-7 study. This study is exploring the use of a potent KRAS inhibitor, adagrasib, in combination with pembrolizumab in patients with advanced or metastatic KRASG12C- mutated non-small cell lung cancer.  Adagrasib has already received accelerated approval in the U.S. for previously treated locally advanced or metastatic NSCLC with a KRASG12C mutation. A previous report from the KRYSTAL-7 study demonstrated encouraging activity in combination with pembrolizumab in the frontline setting for this patient group who also had more than 50% expression of PD-L1. The presentation today described efficacy and safety data for this drug combination across all PD-L1 expression levels.  One hundred and forty-nine patients with a median age of 67 years were treated with the combination, 104 of whom had PD-L1 expression level results available, representing the so-called biomarker population in this trial. The overall response rate for the entire study population was 44%. In the biomarker population, the overall response rate ranged from 36% in those with less than 1% PD-L1 expression to 61% for those with more than 50% expression. For all patients, the median response duration was just over 26 months, and the median progression-free and overall survival rates were 11 and 18.3 months respectively.    For the biomarker population, the median progression-free and overall survival were highest in those patients with more than 50% PD-L1. No new safety issues emerged from this analysis; the most frequent toxicities were nausea, diarrhea, and increases in transaminases. Immune-related toxicities included pneumonitis, hypothyroidism, and hepatitis. These are important results and the results of the phase 3 portion of KRYSTAL-7, which compares first-line therapy with adagrasib plus pembro versus pembro alone in the KRASG12C mutated/PD-L1 more than 50% group, will be informative. For those patients with lower levels of PD-L1 expression, the authors suggest that the treatment escalation may be beneficial, possibly including the addition of chemotherapy.  That concludes today's report. Thanks for listening and I hope you will join me again tomorrow to hear more top takeaways from ASCO25. If you value the insights that you hear on the ASCO Daily News Podcast, please remember to rate, review, and subscribe wherever you get your podcasts.  Disclaimer:  The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  Find out more about today's speaker:    Dr. John Sweetenham    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. John Sweetenham shares highlights from Day 2 of the 2025 ASCO Annual Meeting, including new data on the treatment of ER+/HER2-negative breast cancer and potentially practice-changing results for patients with cutaneous squamous cell carcinoma at high risk of recurrence.  Transcript Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham, your host of the ASCO Daily News Podcast, welcoming you to our special coverage of the 2025 ASCO Annual Meeting. Today, I'll be bringing you my takeaways on selected abstracts from Day 2 of the Meeting. My disclosures are available in the transcript of this episode.  Today's selection features important, new data on the treatment of ER-positive, HER2-negative breast cancer, the use of tumor treating fields in combination with chemotherapy for locally advanced pancreatic cancer, and potentially practice-changing results for patients with cutaneous squamous cell carcinoma at high-risk of recurrence.  Our first selected abstract is LBA1000. This important phase 3 study was presented by Dr. Erika Hamilton from the Sarah Cannon Research Institute in Nashville and evaluated the use of a novel agent, vepdegestrant, in patients with ER-positive/HER2-negative breast cancer, which had progressed after first-line endocrine therapy. Vepdegestrant is a selective oral PROTAC estrogen receptor degrader, which targets wild-type and mutant estrogen receptor through a novel mechanism of action which directly harnesses the ubiquitin-proteasome system to degrade ER. It has potential advantages over fulvestrant, a selective ER degrader which has to be administered intramuscularly and has limited benefit in patients who progress after endocrine therapy plus a CDK4/6 inhibitor.  Building on the encouraging results from the initial phase 1/2 study of vepdegestrant, Dr. Hamilton reported results from the VERITAC-2 global phase 3 trial, comparing this agent with fulvestrant. The patients in the study had already received treatment with hormone therapy and a CDK inhibitor and were randomly assigned to receive treatment with either vepdegestrant (313 patients) or fulvestrant (311 patients). The vepdegestrant was taken orally each day, while the fulvestrant was given intramuscularly on days 1 and 15 of the first cycle of treatment and day 1 of each subsequent treatment cycle. Patients were stratified by the presence of wild-type ER or ESR1 mutation. A total of 43.3% of patients had ESR1 mutations; 136 of those were in the vepdegestrant group and 134 in the fulvestrant group.   For patients with ESR1 mutations, vepdegestrant significantly increased progression-free survival compared with fulvestrant. For patients who received vepdegestrant, the median PFS was 5 months versus 2.1 months for those who received fulvestrant. The clinical benefit rate was 42.1% in the vepdegestrant group vs. 20.2% in the fulvestrant group. The overall response rate was 18.6% in the vepdegestrant group compared with only 4% in the fulvestrant group.  The PFS and response benefits of vepdegestrant were largely restricted to the population with ESR1 mutations. Overall survival data are currently immature. The safety profile was favorable, with fewer than 5% of patients having dose reductions or discontinuation due to toxicity. The most frequent toxicities were fatigue, nausea, and elevated transaminases.  The authors concluded that oral vepdegestrant demonstrates statistically significant and clinically meaningful improvement in progression-free survival compared with fulvestrant in this group of patients with ESR1-mutated ER+/HER2- advanced breast cancer who have progressed after endocrine therapy and a CDK inhibitor. Patients with recurrent disease in this context are now routinely tested for ESR1 mutations, and this agent is for sure a potential treatment option for them.  The next study on today's episode, LBA4005, reports on the use of tumor treatment fields for patients with locally advanced pancreatic cancer. Tumor treatment fields are electric fields which disrupt cell division and may also induce an enhanced immune response, using a non-invasive portable device attached to the skin, and are already approved for the treatment of some cancers, including GBM and non-small cell lung cancer. A previous phase 2 trial, PANOVA-2, confirmed the feasibility and safety of using this approach in combination with gemcitabine plus or minus nabpaclitaxel in pancreatic cancer. In today's presentation, Dr. Vincent Picozzi from the Virginia Mason Medical Center in Seattle presented the results of the PANOVA-3 trial, a phase 3 study comparing gemcitabine and nabpaclitaxel with the same chemotherapy plus tumor treatment fields in patients with locally advanced pancreatic adenocarcinoma.  Five hundred and seventy-one eligible patients were enrolled in the study with a total of 405 (198 in the treatment field group and 207 in the standard arm) comprising the modified intent- to-treat population. The duration of chemotherapy treatment was comparable in both study arms, and patients receiving treatment fields had a median exposure of almost 27 weeks.  Statistically significant improvements were observed for several study endpoints, including overall survival (a median of 16.2 versus 14.2 months), distant PFS (at 13.9 versus 11.5 months) and pain-free survival (at 15.2 versus 9.1 months), all in favor of the treatment fields arm. Although quality of life data were not reported in detail, the authors noted a significant improvement in global health status in the treatment fields arm. Safety data showed a higher level of skin adverse events in the treatment fields arm but were otherwise as expected for the GnP combination.  These are quite remarkable results which add to the growing evidence base for tumor treatment fields and are particularly compelling in this patient group given the substantial improvement in pain-free survival. It will be especially interesting to see the mature analysis of the quality-of-life endpoints in a subsequent report.  The final selection today is Abstract 6001, which describes the C-POST trial, a phase 3 trial of adjuvant cemiplimab versus placebo in patients with high-risk cutaneous squamous cell carcinoma of the skin. This study was presented by Dr. Danny Rischin from the Peter MacCallum Cancer Centre in Melbourne, Australia.   Although surgical resection with or without adjuvant radiation is curative in 90% of patients with cutaneous squamous cell carcinoma, high-risk features, including nodal disease, skin and subcutaneous metastases, perineural invasion and bone involvement, predict for an inferior prognosis.  Cemiplimab, a PD-1 targeting antibody is standard therapy for patients with locally advanced or metastatic disease who are not candidates for curative surgical resection or radiation therapy, with an overall response rate of almost 50%.  The C-POST study evaluated the use of cemiplimab as adjuvant therapy following surgery and radiation in high-risk patients, compared with placebo. Treatment was administered at 3-week intervals for 12 weeks, and then 6-week intervals for a further 36 weeks, with a primary endpoint of disease-free survival. Four hundred and fifteen patients were randomized in the study, 209 to cemiplimab and 206 to placebo. With median follow-up at 24 months, Dr. Rischin reported a highly significant improvement in disease-free survival for the cemiplimab arm, 49.4 months for placebo versus not reached for cemiplimab, with improvements also observed in the rates of locoregional recurrence and distant recurrence at 80% and 60% reductions, respectively. No new safety signals were observed.  This study is potentially practice-changing and provides strong evidence that cemiplimab should be considered the new standard of care in this clinical context.  Thanks for listening today and join me again tomorrow to hear more top takeaways from ASCO25. If you value the insights that you hear on the ASCO Daily News Podcast, please remember to rate, review, and subscribe wherever you get your podcasts.  Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's speaker:   Dr. John Sweetenham   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  

JCO Editorial Fellow Dr. Peter Li and JCO Associate Editor Dr. Andrew Ko discuss the ASCO 25 Simultaneous Publication paper "Lenvatinib Plus Pembrolizumab and Chemotherapy Versus Chemotherapy in Advanced Metastatic Gastroesophageal Adenocarcinoma: The Phase III Randomized LEAP-015 Study." Transcript The guest on this podcast episode has no disclosures to declare. Dr. Peter Li: Hello, everyone, and welcome to our 2025 ASCO Annual Meeting Series where we cover some of the top JCO papers published simultaneously with their abstract presentation at this year's meeting. I'm your host, Dr. Peter Li, JCO Editorial Fellow, and I'm joined by Dr. Andrew Ko, JCO Associate Editor, to discuss the Journal of Clinical Oncology article and abstract presentation "Lenvatinib Plus Pembrolizumab and Chemotherapy Versus Chemotherapy in Advanced Metastatic Gastroesophageal Adenocarcinoma: The Phase III Randomized LEAP-015 Study." Now, let's start off with the relevance of this article. Andrew, can you please explain this to our listeners? Dr. Andrew Ko: Sure. Thanks, Peter. So, this was a very large international study evaluating the combination of lenvatinib and pembrolizumab. And just for context, that combination has been approved for use in other solid tumor types. It's FDA approved for renal cell carcinoma, for example, and endometrial carcinoma. But this study was looking specifically at this combination together with a chemotherapy backbone - so either FOLFOX or CAPOX - and comparing that to what at the time was a standard of care, which was just standard chemotherapy by itself. So, this very large study was intending to look at this particular novel combination. And we can get into some of the nuances of this study because the way that the experimental, the combination arm, was designed was perhaps a little bit more on the unusual side and led to maybe some imbalance in terms of how we think about the respective arms. Dr. Peter Li: Okay. We can definitely talk more about that as we go on. So, what are some of the key results of this study, and how do you think this will impact practice in the future? Dr. Andrew Ko: That's a good question. Technically, it was not a positive study. Well, it was positive in the sense that the co-primary endpoints - which included both progression-free survival and overall survival - so, progression-free survival, it did technically meet its endpoint, both in terms of the overall population and the preplanned subgroup analysis of patients who had a PD-L1 CPS of greater than or equal to 1. So, there was a PFS benefit with the experimental combination - the lenvatinib, pembrolizumab, plus chemotherapy - compared to chemotherapy alone. I will say the benefit was on the more modest side. So, if you even look at the medians, it was not a marked difference. If you look at the hazard ratios, they did meet statistical significance. On the other hand, this did not translate into a benefit for overall survival. So, when you ask, "Well, is this going to inform practice?" I'd have to say no. It highlights, I think, that JCO does want to publish articles that aren't necessarily going to be practice-changing, but that I think offer a lot of insights into trial design and important aspects of investigating novel treatments, even if they don't end up moving the needle in routine clinical practice. Dr. Peter Li: I totally agree with you. I mean, it was significant in terms of progression-free survival, but again, not clinically significant. And then overall survival, the interventional arm actually appeared to do slightly worse overall. Can you make some comments on the strengths and the weaknesses of this study, and where do you see us going from here? Dr. Andrew Ko: So, I think a couple of things worth highlighting in this study, very well designed, more than 800 patients in total. So, first of all, as I mentioned at the beginning, the combination was a little bit unique in terms of patients enrolled to the experimental arm got the combination of lenvatinib, pembrolizumab, together with chemotherapy for a very finite duration. So, that period of chemotherapy they received was only three months. And per protocol, patients then just segued to, quote unquote “maintenance treatment” with just the lenvatinib and pembrolizumab combination. Whereas patients on the control arm, meaning chemotherapy alone, would continue chemotherapy basically in perpetuity until their disease progressed or intolerable toxicity. So, there really was an imbalance in terms of, if you think that chemotherapy or continuing chemotherapy beyond that initial three-month period of time may be significant, that could have had some impact on the robustness or the efficacy of the experimental arm. There were some other aspects in terms of perhaps some differences in the rates of post-progression treatment, in other words, patients going on to receive second-line treatment. I think the other very relevant aspect, Peter, in this study was that the control arm - and no fault of the investigators - but the control arm at the time the study was ongoing just consisted of chemotherapy, FOLFOX CAPOX, by itself, without an immune checkpoint inhibitor, right? And we clearly know, based on results of several large phase III studies, and it's now in standard clinical practice, that we routinely use chemotherapy plus an immune checkpoint inhibitor. Certainly for patients with CPS PD-1/PD-L1 scores that are, well, you could argue greater than 1, or perhaps greater than 5 or 10. But the point being that the control arm of the study probably doesn't reflect what is currently used in clinical practice. And that's just always a challenge in clinical trial design, right? That when a study is designed and when it rolls out, you're always at risk in a rapidly changing and moving field that the standard of care may evolve during the lifetime of that particular trial, which is what I think you see in LEAP-015. Dr. Peter Li: Totally understand. And the survival we see from this study is also roughly similar to the combination of immuno-chemotherapy that is the standard of care today, which is, the authors mentioned, 12 to 14 months. Thank you so much, Andrew, for your input and for speaking about the JCO article "Lenvatinib Plus Pembrolizumab and Chemotherapy Versus Chemotherapy in Advanced Metastatic Gastroesophageal Adenocarcinoma: The Phase III Randomized LEAP-015 Study." Join us again for the latest simultaneous publications from the 2025 ASCO Annual Meeting. Please take a moment to rate, review, and subscribe to all ASCO podcast shows at asco.org/podcasts. Until then, enjoy the rest of ASCO 2025. 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.

JCO Editorial Fellow Peter Li and JCO Associate Editor Eileen O'Reilly discuss the ASCO 25 Simultaneous Publication paper "Tumor-Treating Fields with Gemcitabine and Nab-Paclitaxel for Locally Advanced Pancreatic Adenocarcinoma: Randomized, Open-Label, Pivotal, Phase 3 PANOVA-3 Study." Transcript The guest on this podcast episode has no disclosures to declare. Dr. Peter Li: Hello, and welcome to our 2025 ASCO Annual Meeting series, where we cover some of the top JCO papers published simultaneously with their abstract presentation at this year's meeting. I'm your host, Dr. Peter Li, and I'm joined by JCO Associate Editor Dr. Eileen O'Reilly to discuss the Journal of Clinical Oncology article and abstract presentation "Tumor Treating Fields with Gemcitabine and Nab-Paclitaxel for Locally Advanced Pancreatic Adenocarcinoma: Randomized, Open-Label, Pivotal, Phase 3 PANOVA-3 Study." Now, let's start with the relevance of the article. Eileen, can you explain this study to our listeners? Dr. Eileen O'Reilly: Thanks very much, Peter, for the invitation today to discuss this. Yes, so this is a positive phase 3 trial that was conducted in locally advanced, unresectable pancreas cancer. Patients were randomized to receive either gemcitabine and nab-paclitaxel, international standard, with or without tumor-treating fields. And this is a device like a battery pack that you would wear with a goal to wear that approximately 18 hours a day. And the primary endpoint of this study was overall survival, with key secondary endpoints of tumor response, progression-free survival, looking at pain-free survival, and distant progression-free survival. So, the primary endpoint was met with a median overall survival of 16.2 months compared to 14.2 months on the intervention versus control arm, with a hazard ratio of 0.82. And so that met the pre-specified boundary. There was not an increase in progression-free survival, but there was an increase in control of pain on the tumor-treating fields study. So, it was a large, global study, community, academic sites, randomized 570 people, and it supports what I think we've seen in other difficult-to-treat malignancies using tumor-treating fields, that there's a signal of interest. Dr. Peter Li: Can you speak to some of the strengths and weaknesses of this study? Dr. Eileen O'Reilly: So, strengths: it was a large study. It included community sites, it included academic sites. It included ECOG performance status 0, 1, and some patients with 2. The intent was locally advanced. It probably is fair to say that there were some patients who had more advanced disease based on early progression, based on relatively high CA 19-9 for a percentage of people. But likely that was, with random assignment, that would have presumably fallen out between the arms. The inclusion of patients with a lower performance status is nice to see in large phase 3 studies in pancreas cancer. So, they would be some of the strengths. So maybe some of the limitations are the fact that it's an open-label study - so, always some biases inherent in that. Acknowledging that the primary endpoint was overall survival, presumably that wouldn't be directly influenced by that. And there was an imbalance of women on the control arm, and women do fare a little better in this disease, so possibly kind of weighted one of the study arms a little bit. But nonetheless, I think it was a rigorously designed and rigorously conducted phase 3 trial. It's always hard to fully interpret the signal in locally advanced disease because of the fact that some patients go on to surgery, some patients have a treatment switch of cytotoxic therapy, some patients will go on to radiation. And the endpoint here of overall survival, to a degree, eliminates some of that. So, the benchmark, I think, was generally high here. Dr. Peter Li: Gotcha. And then with these findings and this positive study, how do you foresee this research being implemented and how it will impact clinical practice moving forward? Dr. Eileen O'Reilly: I think there'll be an educational need to introduce this approach to the community and to the pancreas cancer world. Again, there's a precedent in glioblastoma and data from other diseases, so there's some familiarity with this. I think people always want to understand how it works and why it works, and that's something that we'll look forward to hearing more about mechanistically, and also seeing how it can be built upon. And there's some intriguing data with the combination of tumor-treating fields and immunotherapy that's being evaluated in the PANOVA-4 study. So, we'll stay tuned to hear how that reads out in due course. But I think overall, it'll be educational and learning, managing the cutaneous impacts or some skin irritation effects from this, and building on this signal in locally advanced disease. Dr. Peter Li: Well, thank you so much, Eileen, for your time and for speaking about the JCO article, "Tumor Treating Fields with Gemcitabine and Nab-Paclitaxel for Locally Advanced Pancreatic Adenocarcinoma: Randomized, Open-Label, Pivotal, Phase 3 PANOVA-3 Study." Join us again for the latest simultaneous publications from the 2025 ASCO Annual Meeting. Please take a moment to rate, review, and subscribe to all ASCO podcast shows at asco.org/podcasts. Until then, enjoy the rest of ASCO 2025. 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.

JCO Editorial Fellow Dr. Ece Cali Daylan and JCO Associate Editor Dr. Grant McArthur discuss the ASCO 2025 Simultaneous Publication paper "A Phase II (Alliance A091802) Randomized Trial of Avelumab Plus Cetuximab vs. Avelumab Alone in Advanced Cutaneous Squamous Cell Carcinoma (cSCC)." Transcript The guest on this podcast episode has no disclosures to declare. Dr. Ece Cali: Hello, and welcome to our 2025 ASCO Annual Meeting series where we cover some of the top JCO papers published simultaneously with their abstract presentation at this year's meeting. I'm your host, Dr. Ece Cali, and I'm joined by JCO Associate Editor Dr. Grant McArthur. Today, we will discuss Journal of Clinical Oncology article and abstract presentation "A Phase II Randomized Trial of Avelumab Plus Cetuximab Versus Avelumab Alone in Advanced Cutaneous Squamous Cell Carcinoma." Let's start with a brief overview of the clinical trial. This is a randomized phase II trial that compared avelumab plus cetuximab to avelumab in PD-1/PD-L1 antibody-naive patients with advanced cutaneous squamous cell carcinoma. This is a cooperative group study conducted in the United States. Sixty patients were randomized one-to-one and stratified by PD-L1 and HIV status. The primary endpoint was progression-free survival. Patients on the cetuximab plus avelumab arm had a median PFS of 11.1 months, while patients on the avelumab arm had a median PFS of 3 months, corresponding to a hazard ratio of 0.48 with a p-value of 0.018. Grade III or higher treatment-related adverse events occurred in 48% of the patients on the combination arm versus 21% of patients on the avelumab arm. Dr. McArthur, can you please explain to our listeners how you interpret this data? Dr. Grant McArthur: These results are very important because they provide proof of concept for inhibiting PD-L1 as a target when combined with EGFR, so inhibiting PD-L1 with avelumab and inhibiting EGFR with cetuximab, in a randomized trial with a very significant impact in terms of efficacy. So, what this does is it provides proof of concept for inhibiting those targets in cutaneous squamous cell carcinoma of the skin. Avelumab is not approved for cutaneous squamous cell carcinoma of the skin, and so further studies would need to be done, particularly asking the question about combination with the approved PD-1 agents cemiplimab and pembrolizumab. Dr. Ece Cali: I still find the difference in median PFS with various PD-1/PD-L1 inhibitors striking in this context. In this trial, avelumab, as you mentioned, the PD-L1 inhibitor, demonstrated a median PFS of 3 months, whereas PD-1 inhibitors cemiplimab and pembrolizumab have demonstrated longer median PFS in other trials. So, what are some potential reasons for this, and do you think this difference impacts the interpretation of the results here? Dr. Grant McArthur: So, the obvious reason for the differences is that avelumab targets PD-L1, where pembrolizumab and cemiplimab inhibit PD-1, so there could be simply a difference in the target to explain those differences in progression-free survival. However, as you point out, cross-trial comparisons, one has to do with caution because you can, in different phase II studies, enroll different patient populations, which would impact the progression-free survival. So, we have to be cautious about that interpretation. However, given that cemiplimab and pembrolizumab are the approved agents, I think they are the logical ones for further clinical development. Nonetheless, this is still a very important proof-of-concept trial showing that there is a strong clinical signal when you combine EGFR inhibition with inhibition of PD-L1 versus PD-L1 alone. Dr. Ece Cali: I want to highlight some of the safety data presented in this trial as well. The treatment discontinuation rate due to adverse events was much higher in the combination arm, reaching 31% compared to the 14% in the single-agent avelumab arm. The most common grade III adverse events were infusion reaction, rash, and diarrhea in the combination arm. So, these adverse events may affect patients' quality of life significantly. So, what are your thoughts on this, Dr. McArthur? Dr. Grant McArthur: So, the safety data is important. What we're seeing is safety related to each individual agent. So, we have diarrhea and skin rash from the cetuximab, and the infusion reactions is a common toxicity of avelumab. I think what's important, given this is proof of concept inhibiting these targets going forward to further studies, is that agents such as cemiplimab and pembrolizumab have a very low infusion reaction rate. So, the treatment discontinuations due to infusion reaction are unlikely to be an issue with cemiplimab and pembrolizumab when further clinical trials are done. Of course, there is still the issue of diarrhea and skin rash. Now, that can be managed in many patients with EGFR inhibition, you know. However, one would have to await safety data from a significant patient cohort with a combination of cetuximab with either cemiplimab or pembrolizumab, of course, to assess the clinical impact of those safety signals. But I would expect there to be definitely rash and diarrhea as predominant toxicities with those other combinations as well. Dr. Ece Cali: And lastly, I think we touched upon this a little bit, but how do you think this trial impacts the clinical practice, and what are some outstanding questions that need to be addressed in this field in light of the data from this trial? Dr. Grant McArthur: So, the most important outstanding question is - of course, we've already alluded to in our conversation - regarding using anti-PD-1 agents such as pembrolizumab or cemiplimab. So, that needs to be undertaken. Clearly, a randomized trial would be required combining cetuximab with those agents because they are quite active as single agents with impressive response rates and PFS. So, that is the way forward. There's other important clinical questions as well, though. So, patients that get locally aggressive or metastatic cutaneous squamous cell carcinoma of the skin are often immunosuppressed. And so, we do need data in patients that are immunosuppressed, either due to treatment of immune-related disorders - and also organ transplantation. We see a lot of cutaneous squamous cell carcinoma in organ transplant patients. So, these are important patient subsets that would also need to be investigated in further clinical development. However, overall, you know, this is a strong signal, hazard ratio of less than 0.5, and very worthy of further investigation in randomized trials of inhibiting these targets. Dr. Ece Cali: This was a great discussion. Thank you so much for your insight, Dr. McArthur, for speaking about the JCO article "A Phase II Randomized Trial of Avelumab Plus Cetuximab Versus Avelumab Alone in Advanced Cutaneous Squamous Cell Carcinoma." Join us again for the latest simultaneous publications from the 2025 ASCO Annual Meeting. Please take a moment to rate, review, and subscribe to all ASCO podcast shows at asco.org/podcasts. Until then, enjoy the rest of ASCO 2025. 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.

JCO Editorial Fellow Dr. Lauren Shih and JCO Associate Editor Dr. Stephanie Wheeler discuss the ASCO 25 Simultaneous Publication paper "Use of Low-Value Cancer Treatments in Medicare Advantage Versus Traditional Medicare." Transcript The guest on this podcast episode has no disclosures to declare. Dr. Lauren Shih: Hello, and welcome to our 2025 ASCO annual meeting series where we cover some of the top JCO papers published simultaneously with their abstract presentations at this year's meeting. I'm your host, Dr. Lauren Shih, JCO editorial fellow, and I'm joined by JCO Associate Editor Dr. Stephanie Wheeler to discuss the Journal of Clinical Oncology article and abstract presentation "Use of Low-Value Cancer Treatments in Medicare Advantage Versus Traditional Medicare." Let's start with the relevance of the article. Dr. Wheeler, can you explain this to our listeners? Dr. Stephanie Wheeler: Thank you so much. Let's get right into it. So this article is really about understanding different types of Medicare plans and what we should expect to see in terms of their use of low-value treatments for cancer patients. So, as Medicare really is focused on trying to limit the use of low-value cancer treatments, we really need to better understand the drivers of variability. So we know that many cancer patients have multiple treatment options available to them. We also know that the vast majority of older adults beyond age 65 are insured by Medicare, and about half of them are on Medicare Advantage plans, which are serviced by private insurance. And private insurance companies in this case are receiving capitated payments for Medicare beneficiaries to manage their service utilization and reduce costs. So, with respect to Medicare Advantage versus the traditional fee-for-service Medicare, it's not really been known to what extent low-value treatments are differentially used by these types of plans for cancer patients. And so that was really the focus of this article. What the authors found is that across six different types of treatments, in general, the folks who were enrolled in Medicare Advantage plans had reduced use of low-value treatment. So that's a good sign for Medicare beneficiaries. And although the relative difference in that use was somewhat low, this translates to a significant number of Medicare enrollees across the country not receiving these low-value treatments. And of course, this translates to considerable savings at the society level. Dr. Lauren Shih: Are there any additional key results that we should review? Dr. Stephanie Wheeler: Yeah. So I'll tell you just a little bit more about the methods and also their findings. So they looked at six different low-value treatments, and this was in, again, 100% of national Medicare enrollees from 2015 through 2021. So the six low-value treatments that they examined were the use of G-CSFs among patients receiving low-risk chemotherapy and denosumab for those who had castration-sensitive prostate cancer. Then they also looked at four high-cost treatments, including using nab-paclitaxel instead of paclitaxel for patients with breast or lung cancer; second, adding bevacizumab to carboplatin plus paclitaxel for ovarian cancer; third, using brand-name drugs instead of generics when generics were available; and fourth, using biologics instead of biosimilars when biosimilars were available. And these are all, by the way, non-recommended treatments according to a variety of guidelines, including NCCN and ASCO's Choosing Wisely guidelines. So they used the Medicare claims data to examine use of these regimens. They also analyzed results by type of Medicare Advantage plan, whether people were enrolled in a health maintenance organization plan, or an HMO, or a preferred provider organization plan, or a PPO. They also looked at the largest Medicare Advantage insurers—including Aetna, Blue Cross Blue Shield, Cigna, Humana, and UnitedHealth—and limited their analyses to those that had complete encounter data. And what they found across the board is that the enrollees in Medicare Advantage plans generally had lower use of these low-value treatments. And the largest differences between Medicare Advantage and traditional Medicare plans were in the outcomes, including G-CSF use and using denosumab for castration-resistant prostate cancer, and then the combination of bevacizumab, carboplatin, and paclitaxel versus carboplatin and paclitaxel. And all of these had a change in use ranging from about 19% change to 24% change in use. This is significant as a field as we look at ways in which different plan organization can influence use of treatments, particularly given the excess cost of cancer care. This is something we really want to pay attention to. So I'd encourage folks to look more closely at the results by treatment type as well as the results by plan type to see a little bit more about what was going on across different plan types. Dr. Lauren Shih: Great. And are there any outstanding questions that need to be answered? Dr. Stephanie Wheeler: Yes, there always are, of course. I think the study has several strengths that are worth noting. First, they have 100% of Medicare enrollees, so there's national coverage there, which is, you know, quite outstanding. They also use an appropriate choice of analysis to help deal with some of the selection. So they use inverse probability of treatment weights, and they control for practice and county indicators to try to get some realistic adjustment for the selection that happens in terms of how patients are enrolled in different Medicare Advantage versus traditional fee-for-Medicare plans. These statistical approaches are a good idea, but they are limited by the observed variables that we can use for these kinds of adjustments. And so any unobserved—confounding or any unobserved factors that would influence selection in these plans aren't going to be captured well. So preferences, for example, that patients may have about different types of plans when they're insuring themselves and their families may not be captured. Second, the data that are used are only encounter data from those plans with complete records. That may mean that smaller Medicare Advantage insurers or those that don't have as comprehensive records are not included. So this may not be reflective of their practice patterns. And then third, of course, this only looked at six different low-value cancer treatments. It remains to be seen whether this kind of finding extends to other types of low-value cancer treatments, and that's an opportunity for future study. Finally, I would say that we don't exactly know why these patterns exist. It could be that Medicare Advantage plans have different approaches to prior authorization. They could have more in-house quality control and management to really understand, among their population for whom they're receiving Medicare Advantage payments, to really look at care quality and assess Choosing Wisely guidelines. We don't know exactly how that's playing out. And so we need additional data to really figure out what's working here and what are opportunities for future policy and payment innovations that can further reduce low-value care. Dr. Lauren Shih: Great. Thank you so much, Dr. Wheeler, for speaking to us about the JCO article, "Use of Low-Value Cancer Treatments in Medicare Advantage Versus Traditional Medicare." We really appreciate your insights. Dr. Stephanie Wheeler: Thanks for having me. Dr. Lauren Shih: Join us again for the latest simultaneous publications from the ASCO 2025 Annual Meeting. Please take a moment to rate, review, and subscribe to all ASCO podcast shows at asco.org/podcasts. Until then, enjoy the rest of ASCO 2025. 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.

In the first episode of a special daily series during the 2025 ASCO Annual Meeting, Dr. John Sweetenham discusses the results of 2 studies on the treatment of advanced colorectal cancer plus an additional study exploring the association of Medicaid expansion with cancer survival outcomes. Transcript Dr. John Sweetenham: Hello, and welcome to our special coverage of the 2025 ASCO Annual Meeting on the ASCO Daily News Podcast. I'm your host, Dr. John Sweetenham, and I'll be bringing you brief analysis on selected abstracts from each day of the Meeting. My disclosures are available in the transcript of this episode.  Today, I'll be reviewing three abstracts, the first two of which address the treatment of advanced colorectal cancer. Today's first study is Abstract 3501. These data were presented by Dr. Heinz-Josef Lenz from the USC Norris Comprehensive Cancer Center and report on the expanded analysis of the CheckMate-8HW trial. This was a phase 3, international, multicenter trial in patients with MSI-high/MMR-deficient metastatic colorectal cancer, who were randomized between nivolumab (nivo) alone, nivolumab plus ipilumomab (ipi) or investigators' choice of chemotherapy (FOLFOX or FOLFIRI) with or without bevacizumab or cetuximab. The study showed that nivo plus ipi demonstrated superior progression-free survival compared with chemotherapy in the first-line setting and superior progression-free survival compared with nivo alone across all lines of therapy. These results led to the approval of nivo + ipi in the first-line setting in patients with MSI-H/dMMR mCRC in the U.S., the EU, and many other countries.  In today's presentation, Dr. Lenz reported on the expanded analyses of nivo plus ipi versus nivo across all lines of therapy and longer follow-up results for nivo and ipi versus chemo in the first-line setting. With longer follow up (the median is now at 47 months) nivo and ipi continued to show progression-free survival benefit compared with chemotherapy with a median PFS of 54.1 months versus 5.9 months, for a hazard ratio of 0.21.  Additionally, the analysis of the effects on PFS2, defined as the time from randomization to progression after subsequent systemic therapy, start of second subsequent systemic therapy, or death, showed that compared with chemotherapy, first-line nivo and ipi was associated with a 72% reduction in the risk of death or disease progression, despite the fact that 71% of those who progressed following chemotherapy crossed over to receive subsequent immunotherapy. The study also showed that across all lines, nivo and ipi demonstrated superior progression-free survival compared with nivo alone, the median not reached versus 39.3 months, for a hazard ratio of 0.62. No new toxicity signals emerged after further analysis. Most treatment-related adverse events with possible immune etiology were observed within the first six months of therapy. The results for PFS2 are particularly significant. Up to now, there has been some reluctance to use nivo and ipi as first-line therapy, partly because of its toxicity profile and based on the rationale that it would be active after other frontline therapies. The observation in this study that the beneficial effects of nivo and ipi are maintained downstream is compelling. The results suggest that delaying the use of this combination to the second line or later may compromise subsequent PFS and supports the use of nivo and ipi as a standard-of-care frontline option for MSI-H/dMMR metastatic colorectal cancer. Moving on, the next study I'm featuring today is Abstract 3503, presented by Dr. Jeanne Tie from the Peter MacCallum Cancer Centre and the Walter and Eliza Hall Medical Institute of Medical Research from Melbourne, Australia. This study reported the impact of circulating tumor DNA (ctDNA)-guided adjuvant chemotherapy escalation in stage III colon cancer, focused on the primary analysis of the ctDNA-positive cohort from the randomized DYNAMIC-III trial. As background, about 30% of patients with stage III colon cancer will recur following standard-of-care adjuvant therapy with oxaliplatin-based regimens. And current data show that for those patients with high-risk disease, 6 months of chemotherapy is associated with a lower recurrence rate than 3 months. Circulating tumor DNA following initial surgery has been shown to be a strong independent prognostic factor for these patients, but questions remain about how ctDNA can be used for adaptation of treatment. Questions regarding treatment adaptation were addressed in the DYNAMIC-III trials – specifically, does treatment escalation benefit those who are ctDNA positive following surgery, and can therapy be de-escalated for those who are ctDNA negative. The first of these 2 questions – treatment escalation in the positive group – is the subject of this report. One thousand and two patients were randomized in this study, between ctDNA-informed therapy (502) or standard management (500). Of those patients included in the intent to treat cohorts, 129 were ctDNA positive in the ctDNA-informed arm compared with 130 in the standard management arm. Various pre-planned treatment escalation protocols were used, depending on the choice of first-line therapy. With a median follow up of 42.2 months, there was no difference in 3-year relapse free survival between the ctDNA informed group (48%) and the standard management group (52%). There was, however, a highly significant difference in relapse-free survival for patients who cleared ctDNA by the end of treatment compared with those who didn't. The authors concluded that the recurrence risk for this group remains high, at about 50%, after adjuvant therapy and that it increases with higher ctDNA burden, but treatment escalation didn't appear to reduce the recurrence risk. Clearance of ctDNA was associated with a favorable outcome, suggesting that as more effective treatments are developed in the future for this group, ctDNA will likely prove to have major utility. Changing gears now, my final selection for today is Abstract 11006, presented by Dr. Elizabeth Shafer from the American Cancer Society. This study explored the association of Medicaid expansion with 5-year survival after a cancer diagnosis.  Dr. Schafer began her presentation by providing some historical perspective on the impact of the Affordable Care Act on reducing the number of uninsured adults aged less than 65 years in the United States. She then reviewed some recent data on the impact of Medicaid expansion on cancer care, including improved screening rates, improved access to cancer surgery, and an increase in earlier cancer diagnosis. The current study builds on earlier data from the American Cancer Society which showed improved 2-year overall survival for patients with newly diagnosed cancer following Medicaid expansion. The new study reported by Dr. Schafer examined 5-year cause-specific survival in individuals with cancer since Medicaid expansion, analyzed according to cancer type and various demographic and social factors. Using data from more than 813,000 individuals from 26 states that expanded Medicaid compared with more than 610,000 from 12 states that did not, the authors reported that similar improvements in 5-year cause-specific survival were observed in the expansion and the non-expansion states, but when analyzed by other factors, differences in outcome emerged. For example, although similar improvements in survival between expansion and non-expansion states were seen in urban communities, there was a significant improvement of 2.55 percentage points in survival for individuals in rural communities in expansion states compared with those in non-expansion states. Similar trends were observed in high poverty areas, where improvements in survival were superior in expansion versus non-expansion states.  When examined by cancer type, the authors observed greater improvements in 5-year survival for those with pancreatic, lung, and colorectal cancer, possibly due to improvements in screening and early access to treatment.  The authors concluded that those residing in rural and high-poverty areas experienced the most improvement in cause-specific cancer survival following Medicaid expansion. In summary, it's encouraging to see an improving trend in cancer mortality overall, independent of Medicaid expansion, but it's also important to remember that this is yet another study which confirms how implementation of the ACA has improved cancer outcomes and begun to address some of the disparities in cancer care. Join me again tomorrow to hear more top takeaways from ASCO25. And if you value the insights that you hear on the ASCO Daily News Podcast, please remember to rate, review, and subscribe wherever you get your podcasts.   Disclaimer:   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.     Find out more about today's speaker:  Dr. John Sweetenham    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 

This week's episode will be focusing on exciting data to come at the ASCO Annual Meeting 2025 starting with the plenary sessions, then a special focus on the GU abstracts, including prostate CA, renal cell carcinoma, bladder CA, and a quick shout-out for some of the medical education sessions.

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

This episode of Lung Cancer Considered covers the recent FDA approval of Osimertinib after chemo-radiation in EGFR positive NSCLC based on the LAURA trial which was presented at the 2024 ASCO Annual Meeting. Host Dr. Narjust Florez goes in depth with podcast guest Dr. Pamela Samson about the LAURA Trial and its implications for patients and clinicians. Guest: Dr. Pamela Samson is an assistant professor in the Department of Radiation Oncology at Washington University in St. Louis. Dr. Samson specializes in the care of thoracic malignancies and ways to deliver appropriate radiation therapy without compromising efficacy and diminishing toxicities.

Native American oncologist Dr. Amanda Bruegl and Dr. Noelle LoConte discuss culturally tailored interventions and the importance of community engagement to advance cancer prevention, diagnosis, and treatment for Native communities. TRANSCRIPT   ASCO Daily News: Hello and welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. On today's episode, we'll be discussing cancer care for Native American communities who face unique challenges and disparities in accessing and receiving cancer care. I'm delighted to be joined by two oncologists who will be sharing their insights on ways to advance cancer prevention, diagnosis, and treatment through culturally tailored interventions and community-based programs for high-risk Native Americans whose issues are chronically overlooked in the healthcare system, according to experts. Dr. Amanda Bruegl is an associate professor of obstetrics and gynecology at the Oregon Health and Science University School of Medicine. She is a gynecologic oncologist at the OHSU Knight Cancer Institute and a citizen of the Oneida Nation and descendant of Stockbridge-Munsee. Dr. Noelle LoConte is an associate professor of medicine at the University of Wisconsin Madison Carbone Cancer Center where she also serves as a GI medical oncologist, geriatrician and leads community outreach.  Full disclosures are available in the transcript of this episode.  Dr. LoConte and Dr. Bruegl, it's great to have you on the podcast today. Dr. Noelle LoConte: Thanks so much for having me. Dr. Amanda Bruegl: Thank you for having us. ASCO Daily News: Dr. Bruegl, I'd like to start by asking you to tell us a bit about your background and how it has influenced your career and interests as a gynecologic oncologist. Dr. Amanda Bruegl: I grew up in Wisconsin and I have a Native parent and a non-Native parent. And so having an awareness of both cultural influences in my life has really shaped my interest in cancer prevention. Seeing the high rates of preventable death in cancer among Native populations in gynecologic cancers, in particular, has really driven me to dedicate my research career toward decreasing the morbidity and mortality of cervical cancer among Native women. ASCO Daily News: Well, can you tell us about your work in cancer prevention, specifically cervical cancer? The data shows that Native Americans in Oregon get cervical cancer one and a half times more than the general state population and die from it two times more often. What are the factors, the barriers, that are contributing to these high rates of cervical cancer? Dr. Amanda Bruegl: The data in Oregon is actually not just limited to Oregon.  Our group did some work in collaboration with the Northwest Portland Area Indian Health Board Tribal Epidemiology Center, and we found that, as you stated, the rates of cervical cancer are one and a half times that of non-Hispanic Whites and the rate of death is about twice. And that's true for the Pacific Northwest. And if you dig deeper into the literature, you see that these rates are true across Indian Country, sometimes worse. When we looked at the age groups, we found that older women had three times the rate of mortality. So looking at like 45 to 65. As I was looking through the literature to figure out, well, why is this, we found that there are very, very few funded studies that even look at this. We have a known persistent disparity that is chronically understudied and underfunded. And so I'm trying to do work in this arena to explore this further.  A follow up study that we did was looking at whether we are using the prevention tools. So it's common across the United States that we have two very powerful prevention tools. So participation in cervical cancer screening doesn't necessarily prevent cervical cancer, but you can have early detection of pre-invasive disease or detection of early-stage disease, which is highly curable. And then we also have HPV vaccination, something geared towards the youth in our communities across the U.S. HPV vaccination starting at age 9 with a goal of complete vaccination by the age of 12. So we looked at: Are we using these two tools in Indian Country? And what we found was that participation in cervical cancer screening, looking at who is up-to- date among Natives, and we found that overall the population had about 60% rates of up-to- date on cervical cancer screening compared to general US rates, which are in like the high 70s or low 80s. And then when we looked at that age group that has higher rates of mortality, we actually found that there's only about a 50% rate of up-to-date screening. So we know in one arena people aren't participating in screening. And there's a variety of different contributors to that. There's access to care. How far do you have to travel to get to a provider who will provide cervical cancer screening? Among Native women, there's an over 50% rate of history of sexual trauma, sexual violence, pelvic exam trauma. It's a huge barrier to coming in for this very sensitive exam. There is also mistrust with the medical system in general. There's high turnover of providers at Indian Health Service Clinics.  The clinic that I'm currently working at now, so I do outreach at a clinic one day a month and I'm the longest standing doc at that clinic and I'm a consultant who comes one day a month. I've been there since 2016. And so when you can't develop a relationship with a provider and develop trust and there's just this churn of new people every three to six months, developing a relationship to allow someone to feel comfortable with a very personal and private examination can be a huge barrier. On the HPV vaccination side, we found that the numbers for HPV vaccination were pretty optimistic. So the numbers have been going up since our study period started in 2015. The clinics in the Pacific Northwest that are serving Native populations are doing a great job with education, outreach and increasing the numbers. The group with the greatest rates of HPV vaccination are for people assigned female at birth in the 13-18 age group. They are the only group that is approaching the Healthy People 2030 goal. But there's still work to be done in this arena. Those are some big drivers of why this persistent disparity continues. ASCO Daily News: Absolutely. You mentioned some very serious barriers. Sexual trauma, mistrust, long distance to travel to clinics. Looking ahead, can you tell us about potential screening tools that could improve screening? And I also wanted to ask you about innovations you're excited about that could be potentially incorporated into practice to increase the ability and comfort of your patients to screening and access to HPV vaccination. Dr. Amanda Bruegl: So, in terms of cervical cancer screening and how to increase the rates, there are a number of different things in the literature broadly across populations that really show that knowledge and awareness of cervical cancer and cervical cancer screening guidelines is associated with guideline concordant care. And so ensuring that our patients in our communities know and understand what the recommendations are is very important. Efforts to provide education to women in the community, community stakeholders, and culturally tailored content can all be important for increasing the rates of cervical cancer participation.  Another thing that has the potential to really help improve screening rates is HPV self-collection. The FDA just recently approved HPV self-collection which can help empower an individual to do their own testing on their own body and not have someone else place a speculum in a private personal area where they're not comfortable. Some of the tribes in our region are starting to adopt this practice. And I just gave a talk to the regional Indian Health Service medical directors and have had really positive feedback about clinics working towards bringing this into their practice. I hope that the FDA can move forward with allowing patients to do this in the comfort of their own home. Sadly, the FDA in their evaluations decided it had to be a clinic administered test. So someone still has to go through the barrier of finding time to, if they have caregiver responsibilities or work, to have these responsibilities taken care of for someone else so they can drive to a clinic. So these barriers of transportation and caregiving are not addressed by this. It addresses some of the trauma, that barrier. And so I think in the US, we can do better about bringing this like FIT testing to our patients. I really hope and challenge our country to move forward with that a bit more. Geraldine Carroll: Thanks, Dr. Bruegl. I'll come back to you in a moment, but first I'd like to switch gears and address some of the challenges faced by Native communities in Wisconsin that were featured in a fascinating study presented by our guest, Dr. Noelle LoConte, at the recent ASCO Quality Care Symposium. The study found that radon levels in Native lands in Wisconsin were much higher than anticipated and may explain higher rates of lung cancer among Native communities in the state. Radon is the second leading cause of lung cancer in the U.S. So, Dr. LoConte, can you tell us more about this study and your incredible partnership with the Stockbridge-Munsee Band of the Mohican Nation Health Center in this work? Dr. Noelle LoConte: You bet. Thanks for the interest. First of all, I think it's just an incredible privilege to work with all of these communities. So, I wanted to say at the jump that this was a joint project led by the cancer center that I'm affiliated with, but also with the Stockbridge-Munsee community. They approved the project and they designed it with us, and they retain ownership of the data. Data sovereignty is an important issue when you're doing this work. But we came to them wanting to work on something around cancer. I actually thought maybe colorectal cancer screening. But in meeting with the health center and the tribal community members, it became clear that they were more concerned that they had intergenerational rates of cancer, and they felt that they were being poisoned by their land. And that brought me to the state Environmental Health Program. And we looked at some data and realized, one, their lung cancer rates were quite high, but two, their radon testing rates were quite low. And that that was a place where we thought we couldn't make some forward momentum.  So, we designed a program to educate around radon and radon testing and mitigation and then tested all the homes on the reservation. And we successfully tested all homes for radon and then successfully mitigated all the homes that tested over four picocuries per liter, which is the recommended level at which you should mitigate per the EPA, the Environmental Protection Agency. The statewide average for Wisconsin is 10% positive. And amongst homes that had a basement, which is thought to be the highest risk kind of dwelling in the Stockbridge-Munsee Reservation community, the positive rate was 77%. And when you take all the homes together because we had some homes with crawl spaces or slab foundation, it was around, I believe, 55% positive, so much higher than 10%. ASCO Daily News: Well, that data is just striking. Your study certainly illustrates the vital role that cancer centers can play in mitigating structural determinants of health among Native communities, such as with housing quality. Do you think this will inspire a similar approach in other regions of the country?  Dr. Noelle LoConte: Yeah, I think this work was possible because of philanthropy. It is very, very hard to get grant funding for mitigation, in particular. Mitigation is usually done once in the life of the dwelling, but it is very, very expensive. A cheap mitigation is $750, and many are many thousands of dollars especially when you're looking at very rural communities where there's not really a mitigator within hundreds of miles and you have to really negotiate to get somebody to come out there. Every cancer center that's designated by the National Cancer Institute has to have a community outreach and engagement unit or program. I would argue that rather than us generating reports describing disparities, that this kind of work to actually dismantle these determinants of health and move power back into the community is an ideal role for a cancer center. But the funding was definitely a tricky piece of it. And I would hope that we could either envision funding mechanisms that allow for this kind of direct service to communities, or we can continue to work with philanthropic agencies to fund this. ASCO Daily News: Well, looking through a wider lens at the experience of Native communities navigating cancer care, I'd like to ask each of you to comment on how you think the oncology community can better support and serve high-risk Native populations. What message would you like oncologists to take away from this discussion today? Dr. Bruegl, would you like to respond first? Dr. Amanda Bruegl: There's so many layers to needs in our communities. First and foremost, it's important to understand that American Indians and Alaska Natives are sovereign people, sovereign nations. We've been written into the US Constitution as citizens of our own tribes. And it's important to remember that when working with our populations. I think it's also really important to remember that there's treaty law that promised healthcare to our communities. And you see that we are underfunded in all aspects of healthcare, and it's a driver. And people on the healthcare side of things need to remember we represent the failures of the healthcare system to care for our Native communities. Whether or not you wake up in the morning with a goal to help, you have to remember that you represent the institution and the history of this country and are going to be asked to prove yourself in a genuine fashion. And that takes time.  I think for people who are in research, it's really important to think about how do you engage and partner with tribal communities so that we're not chronically left behind and left out of study? We seldom show up in the data, and we have to find our own data. Tribal epidemiology centers have been really paramount in helping tribes get access to their data and analyze their data. But you can see in trial after trial after trial, we're sort of shoved into the other box. And so it's so difficult to understand how the cancer story relates to us and how do we improve it? ASCO Daily News: Thank you, Dr. Bruegl. Dr. LoConte, would you like to comment on this as well? Dr. Noelle LoConte: Yeah. I had jotted down a few points. Many are going to be a little bit of a repetition here, but I think the overarching theme is that the goals for academic medicine often are not the goals of the community that you may be seeking to work in, and so being able to pivot was key to the success of my project, I think.  Can't underestimate the importance of trust. And trust takes a lot of time and a lot of showing up and a lot of being consistent and delivering on what you say you're going to do. And there's a lot of turnover in academic medicine. People leave institutions, move on for promotions. None of that is going to help strengthen these relationships. So I think institutions would be wise to invest in people that stay. I think there should be things like retention bonuses for those of us that stay in places and do community work. It's certainly not the sexy stuff. It's not what gets you in the Plenary at the ASCO Annual Meeting, for example, but I was beyond delighted that I was on the podium for the ASCO Quality Care Symposium. And I think continuing to elevate this work as meaningful and important work, just as important as clinical trials and new drugs, is really important.  I would like to second the motion or the thought that we need to support full funding for the Indian Health Services. It is a promise we made that we continue to underdeliver on that continues to harm patients every day, particularly in the latter half of the year when they run out of funding pretty consistently. For those of us that are non-Native doing this work, to know the history of the community that you're working in and be really mindful of that but also know the role that your institution played in propagating some of these harms. And I think we need more Native physicians that really will help to have concordance with patients and physicians. And so as much as we can support getting more Native folks starting really early – high school, middle school, interested in medicine and biomedical research, all the way through medical school residency fellowship would be really, really impactful. We have a program here founded by Amanda's husband called the Native American Center for Health Professions, or NACHP. It's really a feather in our cap here and I would love to see all medical schools have some sort of pathway program like that. We won't get out of this hole until we start to really take that seriously. ASCO Daily News: Well, thank you so much, Dr. LoConte and Dr. Bruegl for taking the time and showing up for Native communities, and all your work to advance cancer care. We are certainly very grateful for your time today and we will embed links to all of the studies discussed in the transcript of this episode. So thank you again, Dr. LoConte and Dr. Bruegl. Dr. Noelle LoConte: You're welcome. Dr. Amanda Bruegl: Thank you for having us. ASCO Daily News: And thank you to our listeners for your time today. Again, you'll find links to the studies we discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement. Follow today's speakers:  Dr. Amanda Bruegl   Dr. Noelle LoConte @noelleloconte.bsky.social   Follow ASCO on social media:   @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn   Disclosures:   Dr. Amanda Bruegl – No relationships to disclose Dr. Noelle LoConte: Consulting or Advisory Role: Abbvie, PDGx Research Funding: Exact Sciences  

Lung Cancer Considered host Dr. Narjust Florez and Dr. Suresh Ramalingam discuss the recent FDA approval of osimertinib after chemo-radiation in EGFR positive NSCLC. The approval was based, in part, on the results of the LAURA trial, which was presented at the 2024 ASCO Annual Meeting. Guest: Dr. Suresh Ramalingam is the Executive Director, Winship Cancer Institute of Emory University, the Roberto C. Goizueta Distinguished Chair for Cancer Research, and a professor of medicine at Emory University School of Medicine. He is also the editor in chief for the Cancer Journal.

Is your microwave ablation technique up to date? Dr. Ed Kim sits down with guest-host Dr. Kavi Krishnasamy to explore cutting-edge techniques in tumor ablation, with a focus on hepatocellular carcinoma (HCC) treatment with microwave. Dr. Ed Kim is the Director of Interventional Oncology and Professor of Radiology and Surgery in the Division of Vascular and Interventional Radiology at the Mount Sinai Medical Center. --- This podcast is supported by an educational grant from: Varian, a Siemens Healthineers company https://www.varian.com/ --- SYNPOSIS The doctors discuss microwave ablation, radiation segmentectomy, and the decision-making algorithms for choosing appropriate procedures based on lesion characteristics. Dr. Kim touches on the complexities of ablation near the diaphragm and subcapsular lesions, emphasizing the impact of practitioner skill and experience on outcomes. Recent advancements in ablation technologies, software, and device-specific versus device-agnostic applications are also highlighted, along with the importance of post-contrast scans and ultrasound skills. Dr. Kim also delves into emerging technologies such as HistoSonics, augmented reality/virtual reality, and immunotherapy synergies. The doctors underscore the need for a multidisciplinary approach for optimizing patient outcomes and pushing the field toward future innovations. --- TIMESTAMPS 00:00 - Introduction 04:28 - Standardizing Ablation Algorithms 07:51 - Suboptimal Lesion Locations 13:06 - Device Selection and Properties 22:49 - Ablation Planning Software 32:53 - Real-Time Visualization 44:48 - Biopsy and Ablation Techniques 52:14 - Future of Ablation Technology --- RESOURCES Dr. Ed Kim's Publications: https://scholars.mssm.edu/en/persons/edward-kim ACCLAIM Trial: https://www.sio-central.org/ACCLAIM-Trial A multicenter randomized controlled trial to evaluate the efficacy of surgery versus radiofrequency ablation for small hepatocellular carcinoma (SURF trial): Analysis of overall survival: https://ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.4093 Surgery versus thermal ablation for small-size colorectal liver metastases (COLLISION): An international, multicenter, phase III randomized controlled trial. https://ascopubs.org/doi/10.1200/JCO.2024.42.17_suppl.LBA3501 SIR welcomes results of COLLISION Trial, presented at the 2024 ASCO Annual Meeting: https://www.sirweb.org/media-and-pubs/media/news-release-archive/collision-trial-06032024/ HistoSonics: https://histosonics.com/

In our exclusive interview, Dr Kalinsky discussed his top takeaways from the 2024 ASCO Annual Meeting and 2024 ESMO Congress, as well as where he sees the field of breast cancer headed in the future.

Dr. Dionisia Quiroga discusses emerging approaches to personalizing locoregional treatment for breast cancer with Drs. Walter Paul Weber and Charlote Coles, who share insights on tailoring axillary surgery, escalating lymphatic surgery, and implementing hypofractionated radiotherapy. TRANSCRIPT Dr. Dionisia Quiroga: Hello, I'm Dr. Dionisia Quiroga, your guest host of the ASCO Daily News Podcast today. I'm a breast medical oncologist and assistant professor in the Division of Medical Oncology at the Ohio State University Comprehensive Cancer Center. On today's episode, we'll be discussing emerging approaches to personalize locoregional treatment for patients with breast cancer, including many of the latest updates on axillary surgical staging, lymphatic surgery, and evidence-based radiotherapy in the treatment of breast cancer. We're very fortunate to have joining me today for this discussion Dr. Walter Paul Weber, a professor and head at the Division of Breast Surgery at the University Hospital Basel in Switzerland, and Dr. Charlotte Coles, a professor of cancer clinical oncology and the deputy head of the Department of Oncology at the University of Cambridge in the United Kingdom. Our full disclosures are available in the transcript of this episode. Dr. Weber and Dr. Coles, it's very wonderful to have you on the podcast and thank you so much for being here. Dr. Walter Paul Weber: Thank you very much for having us. Dr. Charlotte Coles: Thank you. Dr. Dionisia Quiroga: Now, for many decades prior, axillary lymph node dissection has very much been our standard of care. But recently, axillary surgeries have been able to be gradually deescalated to spare some of our patients from relative and relevant long-term morbidity. There are still some indications in which axillary lymph node dissection still remain. And therefore, we still see breast cancer-related lymphedema, a well-known sequela of the axillary surgery to continue to be prevalent. And I think it's important also to acknowledge that today there's about an estimated 1.5 million cancer survivors who deal with breast cancer-related lymphedema. Now, Dr. Weber, at the recent ASCO Annual Meeting, you and your co-presenters discussed tailoring axillary surgery, escalating lymphatic surgery and implementing evidence-based hypofractionated radiotherapy to really personalize locoregional treatment for people who've been diagnosed with breast cancer. And in addition to that, you and Dr. Coles have also published this work in the 2024 ASCO Educational Book. Can you tell us about some of the recent advances in axillary surgery and what are really the current indications for axillary dissection? Dr. Walter Paul Weber: Yes, I'm happy to do so. So as you've said, we've known for a while that we can omit axillary dissection in patients with clinically known negative breast cancer and negative sentinel nodes. We've known for about 10-15 years that we can omit axillary dissection in patients with one or two positive sentinel nodes in many patients. But what we've learned recently is that we can omit axillary dissection also in patients with one or two positive sentinel nodes who have larger primary tumors who undergo mastectomy or who have extranodal extension. This is a landmark trial that was published just a few months ago, the SENOMAC trial that established this. The remaining indications for axillary dissection are situations where you expect a heavy tumor load in the axilla. For example, when you have more than two positive sentinel nodes or you have a patient with clinically node-positive breast cancer who undergoes upfront surgery and has palpable disease or significant disease on imaging. Patients with locally advanced breast cancer, who are considered by some to be not eligible for nodal downstaging, such as patients with CN2, CN3 disease or CT4 breast cancer. And then the big group of patients who have residual disease after neoadjuvant chemotherapy in the nodes, standard of care is still axillary dissection. But we now have some real-world evidence that it's safe for selected patients with low volume nodal disease left in the nodes, mostly isolated tumor cells, to not undergo axillary dissection. So these are the remaining indications today. Dr. Dionisia Quiroga: Can you speak to situations where maybe even sentinel lymph node biopsies might be omitted? I know you spoke a little bit about the use of imaging in your work. Dr. Walter Paul Weber: Yes, this is correct. So, we started about maybe 7 or 8 years ago to omit sentinel lymph node biopsy in older patients above 70 years of age who have luminal disease, according to recommendations from the Choosing Wisely initiative. And now indeed there are several ongoing randomized trials that investigate if axillary imaging can replace surgical staging of the axilla. And the first of these trials was published recently, the SOUND trial with almost 1,500 patients, who underwent breast conserving surgery and had small tumors and all had a negative ultrasound of the axilla. And then they were randomized into a sentinel lymph node biopsy versus no axillary surgery. And that trial showed non-inferiority of the omission of sentinel lymph node biopsy in these patients. Now, it's a bit early to roll out the Choosing Wisely recommendation to all patients who have a negative ultrasound. The SOUND trial showed that about 14% had a false-negative ultrasound. So, in the control arm, they actually did have a positive sentinel node. And in patients where that one missed sentinel node makes a big difference in terms of systemic therapy, most experts would still recommend sentinel biopsy, and these are patients mainly with HER2-positive or triple-negative breast cancer or premenopausal patients or those who have G3 biology. Dr. Dionisia Quiroga: I think you bring up a very important point. Coming from the side of a breast medical oncologist, we're also very interested to see what these studies show because many of our practices are based on what we find out from our lymph node biopsies. So, I think a lot of interesting prospective studies to look at in the future. Dr. Walter Paul Weber: Absolutely. Dr. Dionisia Quiroga: One other topic we wanted to discuss was local regional management of stage four disease and particularly oligometastatic disease. And this is not a new topic of interest. We've been speaking about this for a long time in breast cancer management, but can you address some of the axillary management strategies that you currently use for stage 4 disease? Dr. Walter Paul Weber: Yes, it depends on your intention. If your intention is to cure the patient, then you would apply all the locoregional standards that apply in the curative setting, which means lymph node biopsy with or without axillary dissection. Now in a palliative situation, it's individualized. Very often you don't touch the axilla and sometimes you open it and just remove palpable disease, trying to minimize morbidity. The question of which intent you should follow is controversial; three out of the four randomized trials did not show a benefit for locoregional surgery in patients with de novo stage 4 disease. However, experts seem to disagree. The last St. Gallen consensus recommendation was in favor of the curative intent in such a patient with oligometastatic disease; 85% favored the curative intent. So there's a bit of discrepancy there, but everybody would agree, and this is what has been done in all of these trials, that if you try to cure the patient, then you should apply the curative standards of sentinel and axillary dissection that you use also in early-stage breast cancer. Dr. Dionisia Quiroga: Thank you. Now, moving on from surgical axillary management and more into lymphedema prevention and treatment. Can you speak to some of the promising advances that have happened in this field? Dr. Walter Paul Weber: Yes, so the best way to prevent lymphedema still is not to perform axillary dissection, which is the number 1 risk factor, which is all the axillary surgery de-escalation research that we've just discussed is all about. Prevention of lymphedema is one major aim of this. Now, once you indicate axillary dissection and you expect the patient to be at high risk – for example, if there are other risk factors such as obesity or neoadjuvant chemotherapy or extended regional nodal radiotherapy, then indeed there are emerging techniques that really seem to work. There is some evidence supporting it, which is categorizable as immediate lymphatic repair basically or bypass. And that is usually in a patient who undergoes axillary dissection, and also undergoes axillary reverse mapping. That allows the identification of the lymph nodes that are probably most relevant to the drainage of the lymphatic fluid from the arm. And then you can try to spare these. But if you decide, and this is effective, there is a consistent body of evidence, not phase 3 trials, but pretty consistent evidence that axillary reverse mapping works just by sparing the identified nodes. But if you decide that you have to remove these nodes as part of the radical concept of axillary dissection, then immediate lymphatic repair is also increasingly being done and is also supported by consistent evidence, even some single center randomized trials, low volume, but all consistently showing quite a striking benefit of this immediate lymphatic repair technique. There are different ways you can do it. You can either use it the microscope, and it's being done by the plastic surgeons, but it's also a simplified technique described that can be used by specialized general and breast surgeons. Both techniques seem to really work based on what we know from the studies, but also based on our common sense. Dr. Dionisia Quiroga: You talked about the procedures that can be offered to patients at time of breast surgery. And unfortunately, many of our patients maybe did not have the availability of those techniques when they undergo their initial breast cancer treatment. Once lymphedema is developed in a limb following breast cancer diagnosis, can you speak to other interventions that can be done to potentially help mitigate lymphedema? Dr. Walter Paul Weber: Right, so for patients who no longer benefit from or wish to further undergo conservative treatment of lymphedema, there are emerging procedures that are now out of my personal comfort zone because they're being performed by plastic surgeons; they use the microscope. There are two groups, the lymphovenous anastomosis and then the real vascular lymph node transfer as a free flap. And both of these procedures (there are no randomized trials yet published), but some really good ones are on the way and currently recruiting based on the evidence we have, which is over 20 observational studies all consistently again showing a benefit in terms of what you can measure in terms of centimeters or with a bioimpedance spectroscopy, or also when you ask the patients, you see quite some dramatic improvements by both of these techniques. And it's increasingly being done. Personally, I strongly believe that it works based on everything we know and understand from lymphedema development, but also prevention and treatment. So I am quite sure that in 5-10 years, we will see much more surgical treatment of patients with lymphedema by highly specialized plastic surgeons. Dr. Dionisia Quiroga: That's my hope as well. Now, another important component of local regional treatment we know is of course radiotherapy. And there have been many incredible advances in breast radiotherapy over the past decades, which has really improved cancer control and decreased side effects in our patients. Dr. Coles, you've led practice changing radiotherapy trials in the past and your research has really influenced international hypofractionation policy. Can you expand upon the emergence of hypofractionated radiation for breast cancer and the effects that it can have on our patient care? Dr. Charlotte Coles: Yes, so thank you very much, Dr. Quiroga. So I think the first thing to say is that radiotherapy hypofractionation isn't a new concept. And in fact, the breast radiotherapy hypofractionation trial started around three decades ago. And the rationale for this was the hypothesis that breast cancer is as sensitive to fraction, which is the treatments that we give, we split it into fractions, is sensitive as late responding tissue. So what does this mean? It means that the small traditional 2 Gy fraction spare tumor and normal tissues equally, so there's no advantage. So therefore, fewer fractions with a larger dose per fraction are worth testing. The problem is there's a concern that hypofractionation might increase the risk of side effects, and that includes the really important one we've been talking about, lymphedema. But we can reduce this risk by reducing the total radiotherapy dose over the whole course. But the question was by how much. So that's why randomized trials were needed. And there's been really high-quality trials with robust radiotherapy quality assurance, and they've been designed in partnership with patients. So just a very quick run through: A landmark trial was the UK START B trial. And this was a pragmatic design that compared 50 Gy in 25 fractions, which was commonly used in the south of the country with 40 Gy in 15 fractions, which was used at that time in the north [of the UK]. And this recruitment was around in the late 1990s and early 2000s. What we knew was that the three-week regimen was actually radiobiologically lower dose. And therefore the results that we got, it wasn't surprising that the 40 Gy was actually gentler on the normal tissue. So that's an advantage for patients. But what was surprising was it wasn't gentler on the tumor and non-inferiority was proven. So this suggests that overall treatment time is important for local control. So this fits with hypofractionation. Way back in 2009, 40 Gy in 15 fractions to both the breast and regional nodes became standard of care in the UK. But five-week nodal and actually breast as well remained standard of care in many countries for many years after that, a little bit to do with the fact that there were few patients treated in the START trial in terms of treating the node. So more recently we've had more randomized trials, particularly for nodal radiotherapy. And this includes the recently reported Danish SKAGEN 1 trial and also the French HypoG-01 trial, which was actually presented at ESMO in Barcelona a couple of weeks ago. So we've now got data for over 5,800 participants in really high-quality randomized trials testing three weeks and five weeks of nodal radiotherapy. And there's no statistically significant difference in late normal tissues for any of these, including lymphedema. So certainly, in my opinion and reflecting in many of the European guidelines, five-week radiotherapy is no longer indicated and three-week nodal radiotherapy is the international standard of care. So, in conclusion, the question is can we hypofractionate even further? So the UK FAST-Forward trial tested three weeks with two different dose levels of one week for the whole breast. Primary endpoint was ipsilateral breast tumor response. More than 4,000 patients participated and this was reported in 2020 with a median follow -up of six years and this was very timely because this is a time of COVID and the results showed non-inferiority for local control with similar late normal tissue side effects and we've also had other results from the UK IMPORT HIGH trial which shows that we can safely deliver a small, highly targeted team of boost simultaneously with the whole breast in all in three weeks. Finally, these two landmark trials have come together for the design of the UK FAST-Forward Boost Study led by my colleague Dr. Anna Kirby. And this is going to test three-week simultaneous integrated boost with two levels of one-week simultaneous integrated boost. And it's also going to test the safety of 5 fraction nodal radiotherapy, including the internal mammary node. Primary endpoint is ipsilateral breast tumor response, multiple normal tissue endpoints, including patient-reported outcomes of course, and the target recall is large with 4,800 participants. So, in summary, I would say that hypofractionation is efficacious, has similarly reduced toxicity. Importantly, it reduces patient burden and that's incredibly important because it means that people can get back on with their life quicker. It reduces health system costs, and also increases equity of access. So we really do need to continue to recruit and design high quality trials in this area. Dr. Dionisia Quiroga: Thank you, Dr. Coles. I think you highlight that there really aren't any downsides to looking into hypofractionated radiotherapy at this point. So excited to see what those future trials yield. And I want to thank you so much, Dr. Weber and Dr. Coles for sharing your valuable insights with us today on the ASCO Daily News Podcast. Dr. Walter Paul Weber: Thank you very much. Dr. Charlotte Coles: Thank you. Dr. Dionisia Quiroga: And thank you to our listeners for joining us today. Our listeners will find a link to our guests' article from the ASCO Educational Book in the transcript of this episode, as well as a link to their presentation from the most recent ASCO Annual Meeting. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcast. 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. Dionisia Quiroga @quirogad Dr. Walter Paul Weber Dr. Charlotte Coles Follow ASCO on social media:     @ASCO on Twitter    ASCO on Facebook    ASCO on LinkedIn    Disclosures: Dr. Dionisia Quiroga: No relationships to disclose Dr. Walter Weber: Honoraria: MSD Dr. Charlotte Coles: No relationships to disclose

Welcome to OncLive On Air®! I'm your host today, Ashling Wahner.  OncLive On Air is a podcast from OncLive®, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.  In today's episode, we had the pleasure of speaking with Tarita Thomas, MD, PhD, MBA, and Rimas Lukas, MD, about abstracts presented during a brain cancer­–focused clinical science symposium at the 2024 ASCO Annual Meeting. Dr Thomas is an associate professor of radiation oncology and Dr Lukas is an associate professor of neurology (neuro-oncology; hospital neurology) at the Northwestern University Feinberg School of Medicine in Chicago, Illinois.  In our exclusive interview, Drs Thomas and Lukas discussed the results of 4 abstracts presented during the symposium. In particular, their discussion highlighted findings with ST101 in window-of-opportunity cohorts of patients with recurrent glioblastoma (GBM), the prognostic utility of cerebrospinal fluid circulating tumor DNA in recurrent high-grade glioma, the genomic drivers of GBM, and preclinical data with navtemadlin (KRT-232) in IDH wild-type GBM.  ___ That's all we have for today! Thank you for listening to this episode of OncLive On Air. Check back on Mondays and Thursdays for exclusive interviews with leading experts in the oncology field.  For more updates in oncology, be sure to visit www.OncLive.com and sign up for our e-newsletters.  OncLive is also on social media. On X, follow us at @OncLive. On Facebook, like us at OncLive, and follow our OncLive page on LinkedIn.  If you liked today's episode of OncLive On Air, please consider subscribing to our podcast on Apple Podcasts, Spotify, Amazon Music, and many of your other favorite podcast platforms,* so you get a notification every time a new episode is posted. While you are there, please take a moment to rate us!  Thanks again for listening to OncLive On Air. 

In Oncology Unplugged, a podcast series from MedNews Week, host Chandler Park, MD, a genitourinary medical oncologist at the Norton Cancer Institute in Louisville, Kentucky, sits down with Tejas Patil, MD, an assistant professor of medicine-medical oncology at the University of Colorado School of Medicine - Anschutz Medical Campus in Aurora. In this episode, Drs Park and Patil discuss key updates from the 2024 ASCO Annual Meeting, including the significance of data from the phase 3 LAURA trial (NCT03521154), where treatment with osimertinib (Tagrisso) following definitive chemoradiotherapy led to an improvement in progression-free survival vs placebo in patients with stage III, EGFR-mutated non–small cell lung cancer (NSCLC). Drs Park and Patil also explore the implications of minimal residual disease (MRD) monitoring in the phase 3 ADAURA trial (NCT02511106) and how liquid biopsy data may influence future treatment timelines. Additionally, they delve into the evolving role of osimertinib in advanced EGFR-mutated NSCLC, based on results from the phase 3 FLAURA2 trial (NCT04035486) and its potential impact on the treatment of patients with brain metastases.

Chadi is joined by Drs. Rana McKay and Petros Grivas to discuss the latest genitourinary oncology research updates from the 2024 ASCO Annual Meeting, covering topics such as the prognostic ability of KIM-1 in kidney cancer, patient-reported outcomes from enfortumab vedotin/pembrolizumab treatment, and the final overall survival update from the JAVELIN Renal 101 trial. The conversation also delves into studies on IO/TKI biomarkers, adaptive trials with ctDNA, and the latest findings from trials like KEYNOTE-426, CLEAR, PSMAfore, and SURE-01. Check out Chadi's website for all Healthcare Unfiltered episodes and other content. www.chadinabhan.com/ Watch all Healthcare Unfiltered episodes on YouTube. www.youtube.com/channel/UCjiJPTpIJdIiukcq0UaMFsA

Did you know 1 in 8 women will get breast cancer in their lifetime? Join Lauren Bright Pacheco for a special episode from the 2024 ASCO Annual Meeting in Chicago, where she dives into the best collaborative approach to breast cancer diagnoses and care. Medical oncologist, Dr. Nan Chen, and breast cancer surgeon, Dr. Sarah Shubeck share how their teamwork benefits breast cancer treatment.See omnystudio.com/listener for privacy information.