Podcasts about Pfizer

We begin with a free-for-all Friday rundown of the latest news stories about the terrible reconciliation bill, bad endorsements from Trump, and more signs of stagflation. The court decision against universal injunctions is one positive story, but there is a huge catch. Also, why is the new CDC director unquestionably defending mRNA shots? Why is this administration continuing the biomedical security state under the mantle of MAHA? Indeed, there is a difference between MAHA and the “medical freedom movement," like the difference between a sword and a shield. We're joined by Hebrew University professor Josh Guetzkow, who just published a pre-print study of a massive population of pregnant women in Israel showing a shocking safety signal from the COVID shots. The COVID shots were associated with a significant increase in fetal deaths among pregnant women who received the shot during the first trimester. Josh discusses how his study is the most airtight to date and how this signal has been ignored until now. He also reviews his findings from two years ago on how the shots given to the public by Pfizer are not the ones studied in clinical trials, yet even the Trump administration continues to assert that they have been studied and properly approved.  Learn more about your ad choices. Visit megaphone.fm/adchoices

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

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A generational shift is predicted as younger conservatives push back against foreign entanglements.BIS vs IMF: Stablecoin Suppression and CBDC Agenda (03:01:39 – 03:03:04)The BIS targets stablecoins in what's described as a battle over who will control future digital money, with CBDCs positioned as tools of global financial dominance.Bitcoin Seen as Hedge Against Fiat Collapse (03:03:05 – 03:07:01)Extreme Bitcoin price forecasts are discussed in the context of fiat currency debasement, with Bitcoin framed as a finite refuge from an increasingly unstable monetary system.Self-Driving Cars as Surveillance and Control Tools (03:13:14 – 03:18:00)Explores how autonomous vehicles collect and transmit driver data, affect social credit scores, and raise concerns about accountability, privacy, and control.War Powers Debate: Trump, Iran, and Congressional Authority (03:18:01 – 03:24:17)Critiques Trump's bombing of Iran without Congressional approval and rebuts claims by Mike Johnson and J.D. Vance that the War Powers Resolution limits presidential authority.MAGA Civil War: Candace Owens vs. Trump on Vaccines and Israel (03:24:18 – 03:29:55) Candace Owens distances herself from Trump over foreign policy while she gave him a pass on Warp Speed vaccines, with commentary on her past praise and growing populist pushback.Trump's Nobel Peace Prize Nomination Mocked (03:30:40 – 03:31:35) Trump is nominated for a Nobel Peace Prize following the Iran ceasefire, provoking ridicule given his role in launching strikes days earlier.Mark Levin vs. Steve Bannon: Neocon Populist Feud over Israel (03:34:20 – 03:39:01)Levin calls for escalated military support for Israel, while Bannon and populist circles reject U.S. involvement. The rift signals deeper ideological divides on the right.Damage from Iranian Missile Strikes on Israel (03:45:10 – 03:47:55)Reports and footage highlight destruction caused by Iranian retaliation, while commentary accuses elites of profiting from wars at civilian expense.Iranian Officials Reported Dead Resurface (03:48:40 – 03:50:35) High-ranking Iranian figures previously declared dead by Israeli sources are shown to be alive, raising doubts about the success of targeted strikes.Follow the show on Kick and watch live every weekday 9:00am EST – 12:00pm EST https://kick.com/davidknightshow Money should have intrinsic value AND transactional privacy: Go to https://davidknight.gold/ for great deals on physical gold/silver For 10% off Gerald Celente's prescient Trends Journal, go to https://trendsjournal.com/ and enter the code KNIGHT Find out more about the show and where you can watch it at TheDavidKnightShow.comIf you would like to support the show and our family please consider subscribing monthly here: SubscribeStar https://www.subscribestar.com/the-david-knight-showOr you can send a donation throughMail: David Knight POB 994 Kodak, TN 37764Zelle: @DavidKnightShow@protonmail.comCash App at: $davidknightshowBTC to: bc1qkuec29hkuye4xse9unh7nptvu3y9qmv24vanh7Become a supporter of this podcast: https://www.spreaker.com/podcast/the-david-knight-show--2653468/support.

Criminal Complaint Filed Over 'Warp Speed Cancer' (01:00:45 – 01:07:05)A complaint filed in France alleges mRNA vaccines caused deadly turbo cancers, implicating global health agencies while ignoring U.S. officials who enabled vaccine rollout. The term 'Warp Speed Cancer' is used to link aggressive cancers with the vaccine campaign.FDA Study Finds Excess DNA in COVID Vaccines (01:12:06 – 01:14:00)An FDA study confirms high levels of DNA contamination in Pfizer's mRNA vaccine, raising concerns over cancer risk and regulatory negligence. Critics compare the lax response to how pollution or car emissions would be handled.COVID Vaccine Removed from CDC Schedule for Children (01:25:54 – 01:27:49)RFK Jr. announces removal of COVID vaccines from the CDC schedule for healthy children and pregnant women, though skepticism is expressed over the true intent and lingering influence of vaccine advocates.CDC Panel Head Accused of Downplaying Vaccine Injuries (01:33:12 – 01:36:50)The new CDC vaccine panel head is criticized for opposing pauses on J&J shots and ignoring adverse event reports, leading to claims of pro-vaccine bias and lack of transparency about injury risks.Cargo Ship Fire Tied to EV Battery Hazards (01:53:00 – 01:59:30)An EV-laden cargo ship sinks after a prolonged fire, raising environmental concerns over lithium battery safety and whether such incidents are factored into EVs' environmental impact.Tesla Robo-Taxi Glitches Spark Regulatory Scrutiny (02:00:36 – 02:07:42)Videos show Tesla's driverless taxis behaving erratically, including stopping in intersections and veering off course. Observers criticize the premature rollout and ineffective safety measures.Markets Shrug Off U.S.-Israel Strike on Iran (02:25:30 – 02:27:04)Gold, silver, oil, and Bitcoin show minimal reaction to joint U.S.-Israel strikes, suggesting either disbelief in the severity of events or market manipulation by major financial actors.Christian Zionism Criticized as Political Idolatry (02:48:33 – 02:52:57)Christian Zionism is condemned as a distortion of theology, accused of leading believers to support war and foreign interventions at the expense of persecuted Christian communities.Pro-Israel Loyalty Test in Conservative Politics (02:52:58 – 03:01:38)Conservative figures are accused of prioritizing loyalty to Israel over American interests. A generational shift is predicted as younger conservatives push back against foreign entanglements.BIS vs IMF: Stablecoin Suppression and CBDC Agenda (03:01:39 – 03:03:04)The BIS targets stablecoins in what's described as a battle over who will control future digital money, with CBDCs positioned as tools of global financial dominance.Bitcoin Seen as Hedge Against Fiat Collapse (03:03:05 – 03:07:01)Extreme Bitcoin price forecasts are discussed in the context of fiat currency debasement, with Bitcoin framed as a finite refuge from an increasingly unstable monetary system.Self-Driving Cars as Surveillance and Control Tools (03:13:14 – 03:18:00)Explores how autonomous vehicles collect and transmit driver data, affect social credit scores, and raise concerns about accountability, privacy, and control.War Powers Debate: Trump, Iran, and Congressional Authority (03:18:01 – 03:24:17)Critiques Trump's bombing of Iran without Congressional approval and rebuts claims by Mike Johnson and J.D. Vance that the War Powers Resolution limits presidential authority.MAGA Civil War: Candace Owens vs. Trump on Vaccines and Israel (03:24:18 – 03:29:55) Candace Owens distances herself from Trump over foreign policy while she gave him a pass on Warp Speed vaccines, with commentary on her past praise and growing populist pushback.Trump's Nobel Peace Prize Nomination Mocked (03:30:40 – 03:31:35) Trump is nominated for a Nobel Peace Prize following the Iran ceasefire, provoking ridicule given his role in launching strikes days earlier.Mark Levin vs. Steve Bannon: Neocon Populist Feud over Israel (03:34:20 – 03:39:01)Levin calls for escalated military support for Israel, while Bannon and populist circles reject U.S. involvement. The rift signals deeper ideological divides on the right.Damage from Iranian Missile Strikes on Israel (03:45:10 – 03:47:55)Reports and footage highlight destruction caused by Iranian retaliation, while commentary accuses elites of profiting from wars at civilian expense.Iranian Officials Reported Dead Resurface (03:48:40 – 03:50:35) High-ranking Iranian figures previously declared dead by Israeli sources are shown to be alive, raising doubts about the success of targeted strikes.Follow the show on Kick and watch live every weekday 9:00am EST – 12:00pm EST https://kick.com/davidknightshow Money should have intrinsic value AND transactional privacy: Go to https://davidknight.gold/ for great deals on physical gold/silver For 10% off Gerald Celente's prescient Trends Journal, go to https://trendsjournal.com/ and enter the code KNIGHT Find out more about the show and where you can watch it at TheDavidKnightShow.comIf you would like to support the show and our family please consider subscribing monthly here: SubscribeStar https://www.subscribestar.com/the-david-knight-showOr you can send a donation throughMail: David Knight POB 994 Kodak, TN 37764Zelle: @DavidKnightShow@protonmail.comCash App at: $davidknightshowBTC to: bc1qkuec29hkuye4xse9unh7nptvu3y9qmv24vanh7Become a supporter of this podcast: https://www.spreaker.com/podcast/the-real-david-knight-show--5282736/support.

"Older adults have this special clarity about who they are and what they want, which is incredibly inspiring," says Dr. Julia Hiner, explaining, in part, why she loves her work as a geriatrician in Houston, Texas. She also enjoys the challenge of the medical complexity these patients present and the opportunity it creates to see the patient as a whole person. In fact, as you'll hear in this upbeat conversation with Raise the Line host Lindsey Smith, there's almost nothing about geriatrics that Dr. Hiner does not enjoy, which explains her passion for teaching the subject at McGovern Medical School at the University of Texas Health Science Center in Houston and trying to convince more students to pursue it as their specialty.  The need is great, given that there are only 8,000 geriatricians in the US despite a rapidly growing senior population. Tune in to learn why Dr. Hiner thinks clinicians avoid the field and the steps that can be taken to improve the situation, including requiring courses in geriatrics. You'll also learn about the importance of capacity assessments, the troubling, and under-reported, problem of elder mistreatment, ageism among health professionals and much more in this super informative episode. Mentioned in this episode:University of Texas Health Science Center at Houston McGovern Medical School  If you like this podcast, please share it on your social channels. You can also subscribe to the series and check out all of our episodes at www.osmosis.org/raisethelinepodcast

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

In the latest episode of Founded & Funded, Madrona Partner Vivek Ramaswami sits down with Harley Sugarman, founder and CEO of Anagram, to unpack how one pivot, a flood of cold outreach, and relentless focus on behavior change transformed a niche tool into an enterprise platform serving companies like Disney and Pfizer.   From landing enterprise logos off of nothing but wireframes, to outmaneuvering the 800-lb gorilla in a legacy industry — Harley's tactics are a masterclass for any founder trying to stand out in a crowded market. Transcript: https://www.madrona.com/how-anagram-landed-disney-with-cold-outbound-security-awareness-training Chapters:  (00:00) Introduction (01:53) Harley Sugarman's Background and Journey (03:24) Founding Anagram (04:21) Initial Vision and Pivot (05:50) Challenges and Market Realities (06:54) Customer Feedback and New Direction (09:25) Executing a Startup Pivot (11:31) Cold Outreach Success (14:20) Security Awareness Training that works (18:52) Competing in a Crowded Market (24:48) Enterprise Sales Strategy (27:04) Fundraising Journey (28:54) Choosing the Right Investors (33:32) Advice for Founders (36:33) Future of Security Training

In this podcast episode, Miguel Regueiro, MD, discusses developing the medical home model for patients with IBD, technological advances for patients in GI and more. •    Intro :58 •    The interview/about Regueiro 1:03 •    Tell us about your family and where you grew up. 1:24 •    How did you get interested in medicine? 2:16 •    Who were your early influences?  4:18 •    What is the medical home? 5:57 •    How did you develop the idea to apply the medical home model to IBD? 7:45 •    Did you get any funding from the payers for this model to keep costs under control for this patient population? 10:57 •    Why hasn't this model become standard of care for patients with complex IBD? 14:13 •    What has worked, and what hasn't worked when it comes to adopting an integrative care medical home model? 18:15 •    Are there themes patients share as to why they wouldn't want to be enrolled in a medical home? 21:28 •    What motivated your change to go from UPMC to become the GI Chief of Cleveland Clinic? 23:09 •    What have you learned in this position at Cleveland Clinic? 25:23 •    Are you spending a lot of time on the business side of care as opposed to the patient side? 26:34 •    How would you recommend that people prepare for having a position like this? 27:34 •    Are you seeing a shift in excitement over taking on leadership roles outside of traditional academics? 30:02 •    With our clinical tool chest changing so rapidly, is there a common theme that you use to guide the strategy of the institute on what to invest in? 35:06 •    What are the challenges that you still see in the ways we are using telehealth? 39:05 •    What are some of the most exciting things you see on the horizon in the realm of IBD management? 40:26 •    Thank you, Miguel 42:55 •    Thanks for listening 45:11 Miguel Regueiro, MD, is the chief of the Digestive Disease Institute at Cleveland Clinic, and professor in the department of medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University. We'd love to hear from you! Send your comments/questions to guttalkpodcast@healio.com. Follow us on X @HealioGastro @sameerkberry @umfoodoc. For more from Regueiro, follow @MRegueiroMD on X. Disclosures: Berry and Chey report no relevant financial disclosures. Regueiro reports being on the advisory boards of and consulting for Abavax, Abbvie, Amgen, Biocon, BMS, Boehringer Ingelheim Pharmaceuticals Inc. (BIPI), Celgene, Celltrion, Gilead, Genentech, Johnson and Johnson, Lilly, Merck, Organon, Pfizer, Prometheus, Roche, Salix, Sanofi, Takeda and UBC.

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 

AUA2025: AUA Advanced Prostate Cancer Course CME Available: https://auau.auanet.org/node/43035 At the conclusion of this activity, participants will be able to: 1. Describe appropriate use of genetic testing (germline) and understand the importance of genetic counseling. 2. Describe appropriate use of somatic testing and treatments related to specific genetic alterations. 3. Identify appropriate combination therapy with ADT plus novel androgen access therapies and chemotherapy. Early treatment intensification including patient selection and adverse effects and benefits will be discussed in mHSCPC. 4. Explain the treatments for non-metastatic CRPC and oncologic outcomes, with recommendations based on AUA/SUO Guidelines. 5. Counsel patients on available treatment options for CRPC as well as combination therapy and sequencing based on the latest AUA/SUO Guidelines. ACKNOWLEDGEMENTS: This educational activity is supported by independent educational grants from: Astellas, Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC, Lantheus Medical Imaging, Novartis Pharmaceuticals Corporation, Pfizer, Inc.

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

A new study coauthored by Dr. Vibeke Manniche shows birth rates plummeted in 2022. The Czech study reveals women vaccinated for COVID-19 had significantly lower conception rates than unvaccinated women from June 2021 to 2023. Using nationwide data from the Institute of Health Information and Statistics, researchers analyzed 1.3 million women aged 18-39. By late 2021, 70% were vaccinated, mostly with Pfizer or Moderna mRNA shots. By 2022, conception rates were 1.5 times higher in unvaccinated women. Dr. Vibeke Manniche, MD, PhD, is a Danish epidemiologist and author of 35 books on health and family. She opposed COVID lockdowns, citing disproportionate measures. More at https://x.com/mannichevibeke Jeffrey Tucker is Founder and President of the Brownstone Institute. He is also Senior Economics Columnist for Epoch Times, author of 10 books, including Liberty or Lockdown, and thousands of articles in the scholarly and popular press. He speaks widely on topics of economics, technology, social philosophy, and culture. Follow him at https://x.com/jeffreyatucker and https://brownstone.org/ 「 SUPPORT OUR SPONSORS 」 Find out more about the brands that make this show possible and get special discounts on Dr. Drew's favorite products at ⁠⁠⁠⁠⁠⁠⁠⁠⁠https://drdrew.com/sponsors⁠⁠⁠⁠⁠⁠⁠⁠⁠  ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ • ACTIVE SKIN REPAIR - Repair skin faster with more of the molecule your body creates naturally! Hypochlorous (HOCl) is produced by white blood cells to support healing – and no sting. Get 20% off at ⁠⁠⁠⁠⁠⁠⁠⁠⁠https://drdrew.com/skinrepair⁠⁠⁠⁠⁠⁠⁠⁠⁠ • FATTY15 – The future of essential fatty acids is here! Strengthen your cells against age-related breakdown with Fatty15. Get 15% off a 90-day Starter Kit Subscription at ⁠⁠⁠⁠⁠⁠⁠⁠⁠https://drdrew.com/fatty15⁠⁠⁠⁠⁠⁠⁠⁠⁠ • PALEOVALLEY - "Paleovalley has a wide variety of extraordinary products that are both healthful and delicious,” says Dr. Drew. "I am a huge fan of this brand and know you'll love it too!” Get 15% off your first order at ⁠⁠⁠⁠⁠⁠⁠⁠⁠https://drdrew.com/paleovalley⁠⁠⁠⁠⁠⁠⁠⁠⁠ • VSHREDMD – Formulated by Dr. Drew: The Science of Cellular Health + World-Class Training Programs, Premium Content, and 1-1 Training with Certified V Shred Coaches! More at ⁠⁠⁠https://vshredmd.com/⁠⁠⁠ • THE WELLNESS COMPANY - Counteract harmful spike proteins with TWC's Signature Series Spike Support Formula containing nattokinase and selenium. Learn more about TWC's supplements at ⁠⁠⁠⁠⁠⁠⁠⁠⁠https://twc.health/drew⁠⁠⁠⁠⁠⁠⁠⁠⁠ 「 MEDICAL NOTE 」 Portions of this program may examine countervailing views on important medical issues. Always consult your physician before making any decisions about your health. 「 ABOUT THE SHOW 」 Ask Dr. Drew is produced by Kaleb Nation (⁠⁠⁠⁠⁠⁠⁠⁠⁠https://kalebnation.com⁠⁠⁠⁠⁠⁠⁠⁠⁠) and Susan Pinsky (⁠⁠⁠⁠⁠⁠⁠⁠⁠https://twitter.com/firstladyoflov⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠e⁠⁠⁠⁠⁠⁠⁠⁠⁠). This show is for entertainment and/or informational purposes only, and is not a substitute for medical advice, diagnosis, or treatment. Learn more about your ad choices. Visit megaphone.fm/adchoices

 ”Money Is A Wise And Loving Force” Join me and my guest Judy Wilkins-Smith (judywilkins-smith.com), Founder of System Dynamics for Individuals & Organizations. Judy is a highly regarded international, organizational, individual and family patterns expert, systemic coach, and trainer. For two decades, Judy has been assisting high-performance individuals, Fortune 500 executives, organizational teams and legacy families to create lasting breakthroughs and peak performance with systemic constellation work. Her clients include NASA, Microsoft, Pfizer, Exxon Mobil, Shell, Chevron, JP Morgan, Kraft Heinz, MARS Petcare North America, MARS LATAM, and the William Morris Agency.  SPONSORED BY: Power of You! Find out more at https://leader.blainebartlett.com/power-of-you Summary In this conversation, Judy Wilkins-Smith and Blaine explore the transformative power of family constellation work and emotional DNA. They discuss how understanding and addressing unconscious patterns can lead to personal and organizational breakthroughs. Judy shares her insights on the importance of choice, mindset, and the role of money as a generative energy. The conversation culminates in an invitation to an upcoming event focused on helping individuals and organizations become unstoppable by leveraging their emotional DNA. Takeaways Family constellation work reveals unconscious patterns affecting individuals and organizations. Emotional DNA encompasses inherited patterns of thoughts, feelings, and actions. Transformational experiences can lead to profound shifts in mindset and behavior. Choice is a fundamental aspect of personal growth and development. Organizations can benefit from understanding their patterns of give and receive. Money is a wise and loving force that should be embraced, not feared. Every challenge presents an opportunity for growth and learning. The importance of aligning head, heart, and gut for effective decision-making. Participants in constellation work often experience immediate and lasting transformations. Learn more about your ad choices. Visit megaphone.fm/adchoices

This engaging and informative webinar explores the role of OX40 and OX40L in pediatric dermatology. OX40: Innovative Insights and Therapeutic Potential in Pediatric Dermatology brings together experts in the field to discuss emerging research, mechanisms of action, and the implications of targeting the OX40 pathway for treating chronic inflammatory skin diseases in children. To view the video version of this webinar, please click here. Disclosures:Lawrence Eichenfield, MD has served as a consultant, speaker, advisory board member, or investigator for AbbVie, Acrotech, Almirall, Amgen, Apogee, Arcutis, Attovia, Bristol Myers Squibb, Castle Biosciences, CorEvitas, Dermavant, Eli Lilly, Forte, Galderma, Incyte Corporation, Janssen, Johnson & Johnson, LEO Pharma, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi Genzyme, Target RWE, T-Rex, and UCB.Eric Simpson, MD reports personal fees from AbbVie, Aclaris Therapeutics, Amgen, Arcutis, Astria Therapeutics, Attovia Therapeutics, Inc., Bambusa Therapeutics Inc., Castle, CorEvitas, Dermira, Eli Lilly, Evomunne, FIDE, Impetus Healthcare, Incyte, Innovaderm Reche/ Indero, Inmagene Biopharmaceuticals, Janssen, LectureLinx (LLX), Leo, NUMAB Therapeutics AG, Pfizer, Recludix Pharma, Regeneron, Roche Products Ltd, Sanofi-Genzyme, SITRYX TherapeuticsEric Simpson, MD reports grants (or serves as Principal investigator role) for AbbVie, Acrotech, Amgen, Arcutis, ASLAN, Castle, Dermavant, CorEvitas, Dermira, Eli Lilly, Incyte, Pfizer, Regeneron, Sanofi-Genzyme, Target, VeriSkinJoy Wan, MD Sun Pharmaceuticals - consulting (DMC), Astria Therapeutics - consulting (ad board), Galderma - fellowship funding (paid to Johns Hopkins)

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma and Biotech world.Gilead has received approval for a twice-yearly HIV drug, Lenacapavir, which will be marketed as Yeztugo, potentially redefining the prep market. In other news, biopharma deal premiums show intense negotiations, with Sanofi paying a high premium for Vigil Neuroscience and Novartis acquiring Regulus for $800 million upfront. BioNTech is merging with CureVac after previously criticizing its failed COVID vaccine program. AI is becoming crucial in precision oncology, with companies like AstraZeneca and Pfizer using computational power to design trials and understand challenging cancers better. Intellia Therapeutics aims to transform lives with genome editing treatments.

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

This episode covers: Cardiology This Week: A concise summary of recent studies Heart disease risk: Framingham Heart Study insights Sudden death in female athletes Mythbusters: Owning a pet reduces the risk of heart disease Host: Susanna Price Guests: Carlos Aguiar, Sabiha Gati, Vasan Ramachandran Want to watch that episode? Go to: https://esc365.escardio.org/event/1809 Want to watch that extended interview on sudden death in athletes? Go to: https://esc365.escardio.org/event/1809?resource=interview   Disclaimer ESC TV Today is supported by Bristol Myers Squibb and Novartis. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsors. The ESC is not liable for any translated content of this video.The English-language always prevails. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC.   Declarations of interests Stephan Achenbach, Sabiha Gati, Nicolle Kraenkel, Susanna Price and Vasan Ramachandran have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

Host: Susanna Price Guest: Sabiha Gati Want to watch that extended interview on LDL management? Go to: https://esc365.escardio.org/event/1809?resource=interview Want to watch the full episode? Go to: https://esc365.escardio.org/event/1809   Disclaimer ESC TV Today is supported by Bristol Myers Squibb and Novartis. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsors.  This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. The ESC is not liable for any translated content of this video. The English-language always prevails.   Declarations of interests Stephan Achenbach, Sabiha Gati, Nicolle Kraenkel and Susanna Price have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada.  Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

Today, we cover ASCO 2025 in the genitourinary space, specifically bladder and renal cancer. Dr. Enrique Grande, a renowned oncologist and Program and Clinical Research lead of MD Anderson Cancer Centre, Madrid, joins us. This is a mega episode where we cover AMPLITUDE, JAVELIN MEDLEY, CHECKMATE 901 and NIAGARA, advancing urothelial cancer care; SEAR 02 and the CReST trial, pushing boundaries in bladder cancer; CHECKMATE 214; LITESPARK-005 and LITESPARK-004, showcasing belzutifan's promise; and KEYNOTE-564, adjuvant therapy for kidney cancer. Stay tuned for an insightful conversation on how these trials may be transforming patient outcomes!Studies discussed in the episode:CHECKMATE 901NIAGARACHECKMATE 214CREST trialSEAR 02LITESPARK 004/005AMPLITUDEJAVELIN MEDLEYFor more episodes, resources and blog posts, visit www.inquisitiveonc.comPlease find us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of AlisiaBeats: https://pixabay.com/users/alisiabeats-39461785/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice.Oncology for the Inquisitive Mind is recorded with the support of education grants from our foundation partners Pfizer, Gilead Pharmaceuticals and Merck Pharmaceuticals. Our partners have access to the episode at the same time you do and have no editorial control over the content. Hosted on Acast. See acast.com/privacy for more information.

Christina Rahm, MS, PhD, EdD, is an internationally recognized entrepreneur, scientific leader, spokesperson, and innovator in the health and wellness space. Her overall approach to her groundbreaking work is to dismantle the barriers blocking the way to optimal health by identifying the root causes of issues and then addressing them scientifically and holistically.Full Podcast Link https://bit.ly/DrChristinaRahmPodcast A living embodiment of her motto, "The most important environment is yours," she travels the world presenting, lecturing, and educating the private and public sectors about the bold new world of nutraceuticals, wellness strategies, and environmental solutions, ultimately paving the way for the advancement of humanity. With multiple master's-level, doctoral-level, and honorary doctorate degrees in the fields of rehabilitation counseling, psychology, philosophy, and strategic sciences, Dr. Rahm also holds certifications from Harvard and Cornell in nanotechnology, nutrition, and pharmaceutical management. In addition to helming her own far-reaching enterprises, she has served as a medical, clinical, and research scientist for such notable pharmaceutical and biotechnology labs as Johnson & Johnson, UCB, Alexion, and Bristol Myers Squibb, and she has worked on the corporate side for Pfizer, Biogen, and Janssen, among others. A wife, mother, author, scientist, formulator, artist, influencer, and humanitarian, Christina Rahm is a powerhouse of energy and focus, devoted to human progress in all its forms and driven to contribute to positive change across the planet.

AUA2025: Should I Order a PET Scan? Integrating Molecular Imaging Into Urologic Oncology Clinical Practice: Current Approaches and Future Opportunities CME Available: https://auau.auanet.org/node/43003 At the conclusion of this activity, participants will be able to: 1. Analyze the best available evidence on the current diagnostic imaging options for prostate, kidney, bladder, and testis cancer detection, staging, and follow-up. 2. Identify the benefits of combined functional and anatomic information gained through accurate matching of anatomic (CT/MRI) and functional (PET) images 3. Debate the strengths and limitations of emerging molecular imaging techniques compared to existing diagnostic tests. 4. Optimally stage urologic oncology patients by understanding the performance characteristics of standard and emerging molecular imaging modalities. 5. Identify the emerging role of PET imaging and novel radiotracers to assess chemotherapy and immunotherapy response. 6. Formulate a strategic plan for appropriate integration of molecular imaging into clinical practice. ACKNOWLEDGEMENTS: This educational activity is supported by independent educational grants from: Astellas, Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC, Lantheus Medical Imaging, Novartis Pharmaceuticals Corporation, Pfizer, Inc.

9:25 – 9:37 (12mins) Weekly Feature: "FAKE NEWS!!" The Mainstream Media has Gone From being The “Legacy Pfizer Media” To All Out Propagandists 9:41 – 9:56 (15mins) CFACT GUEST: Melanie Collette cfact.org @CFACTSee omnystudio.com/listener for privacy information.

With over a decade of experience in Office and Industrial Real Estate Tenant/User Representation across Costa Rica and Central America, Alvaro has worked closely with leading multinational companies such as Roche, Microsoft, Penumbra, Pfizer, Auxis, DHL, and others with operations in the region.He has collaborated both within his global firm and alongside competing firms that lack a direct presence in these markets—always respecting the source of business and prioritizing strong, long-term broker-to-broker relationships, regardless of the CRE firm involved. His specialties include site selection, buyer representation, build-to-suit (BTS) projects, and lease negotiations, all with the goal of helping companies secure the right space to support their growth and operations.Recognized as a top producer in the region, he is actively expanding his network and building partnerships with brokers and companies interested in nearshoring to Costa Rica and Central America.Connect with Alvaro:LinkedIn: https://cr.linkedin.com/in/ajcortes--

Audio roundup of selected biopharma industry content from Scrip over the business week ended 13 June 2025. In this episode: breaking down big pharma's executive pay; US vaccine panel upheaval; Merck's RSV approval; MFN and Japan; and the future of Pfizer and Arvinas's partnership. https://insights.citeline.com/scrip/podcasts/scrips-five-must-know-things/quick-listen-scrips-five-must-know-things-BC44NPMNMNGMXP5X4STR4ZAFU4/ This episode was produced with the help of AI text-to-voice and voice emulation tools. Playlist: soundcloud.com/citelinesounds/sets/scrips-five-must-know-things

Today, we're joined by Professor Anthony Joshua, head of Medical Oncology at St. Vincent's Hospital, Sydney, and a global leader in prostate cancer and melanoma. In this episode, Professor Joshua discusses multiple trials including AMPLITUDE, advancing prostate cancer therapies; CAN 2409, exploring immunotherapy; ARANOTE, showing darolutamide's impact on progression-free survival; the prognostic significance of PSA 0.2; and the landmark STAMPEDE study. Join us for a deep dive into these game-changing studies. Let's begin! It's a jam-packed episode!Studies discussed in the episode:AMPLITUDECAN2409ARANOTESTAMPEDE*AND MORE!For more episodes, resources and blog posts, visit www.inquisitiveonc.comPlease find us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of AlisiaBeats: https://pixabay.com/users/alisiabeats-39461785/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice.Oncology for the Inquisitive Mind is recorded with the support of education grants from our foundation partners Pfizer, Gilead Pharmaceuticals and Merck Pharmaceuticals. Our partners have access to the episode at the same time you do and have no editorial control over the content. Hosted on Acast. See acast.com/privacy for more information.

Chinese biotech stocks are breaking out—with deals involving Pfizer, Bristol-Myers Squibb, and BioNTech rewriting the playbook for global pharma partnerships. But will the rally last? Back in Singapore, banks like DBS, OCBC, and UOB are buying back shares at scale. And Q&M Dental’s CEO is doubling down on his stock. Plus: Amazon and Walmart explore launching their own stablecoins—could Visa and Mastercard be in trouble? Hosted by Michelle Martin with Ryan Huang, this episode also touches on Novo Nordisk, Oracle, Pop Mart, Emirates, and Jardine Matheson as we unpack the week in markets. Companies mentioned in this episode: Pfizer, Bristol-Myers Squibb, BioNTech, 3SBio, DBS, OCBC, UOB, Q&M Dental, Amazon, Walmart, Visa, Mastercard, Novo Nordisk, Oracle, Pop Mart, Emirates, Jardine Matheson, SATS, SGX.See omnystudio.com/listener for privacy information.

In this episode, we unpack game-changing insights from ASCO 2025 with a spotlight on breast cancer. Joining us is Dr. Adam Brufsky, a trailblazing oncologist and professor at the University of Pittsburgh, with 30 years of experience, whose expertise has helped shape the direction of treatment. Trials discussed include the SERENA-6 trial, which examines camizestrant plus CDK4/6 inhibitors in HR-positive, ESR1 mutation breast cancer; the DESTINY-Breast09 trial, highlighting trastuzumab deruxtecan in combination with pertuzumab; and the INAVO120 trial, revealing inavolisib's triplet therapy response in PIK3CA-mutated, HR-positive, HER2-negative disease. Join us for a deep dive into these game-changing findings and their impact on patient care.Studies discussed in the episode:SERENA-6DESTINY BREAST 09INAVO 120For more episodes, resources and blog posts, visit www.inquisitiveonc.comPlease find us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of AlisiaBeats: https://pixabay.com/users/alisiabeats-39461785/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice.Oncology for the Inquisitive Mind is recorded with the support of education grants from our foundation partners Pfizer, Gilead Pharmaceuticals and Merck Pharmaceuticals. Our partners have access to the episode at the same time you do and have no editorial control over the content. Hosted on Acast. See acast.com/privacy for more information.

America Out Loud PULSE with Malcolm Out Loud and Dr. Mary Talley Bowden – Is turbo cancer inevitable? How long after the vaccine is it safe to donate blood or organs, as well as have sexual relations? Is methylene blue really safe? As the mRNA is synthetic, does this mean that we will never break down Pfizer or Moderna? Will all the vaccinated be dead within 10 years?

"It was pretty apparent to me that something was going on with him," says Kristi Levine, describing the realization that, based on her experience as a Montessori teacher, her infant son, Trey, was missing developmental milestones. Unfortunately, Kristi's hunch turned out to be correct and Trey was later diagnosed with a rare genetic mutation called CACNA1A which is impacting his motor skills, balance, coordination and speech. Kristi and her husband, Eric, join host Michael Carrese on this installment in our Year of the Zebraseries to help us understand the disorder and its implications for Trey and their family, which includes Trey's older sister Stella.  “There's a lot of guilt involved in being a parent of a child who has a disability because you never feel like you're doing enough,” shares Eric, even though they both work full time and have becoming experts at juggling work, caregiving, advocating, and volunteering with the CACNA1A Foundation. In this candid interview, Eric and Kristi discuss the challenges of parenting a child with complex medical needs, the importance of community support, the ongoing search for treatment options, and share some advice for clinicians caring for patients and families living with rare disorders. “We just want medical professionals to respect and understand what we're dealing with on a day-to-day basis and to see our kids holistically, and not just try to fix the problem medically. Understand that for us, the biggest thing that we want for our kids is just their quality of life.”Mentioned in this episode:CACNA1A Foundation If you like this podcast, please share it on your social channels. You can also subscribe to the series and check out all of our episodes at www.osmosis.org/raisethelinepodcast

America Out Loud PULSE with Malcolm Out Loud and Dr. Mary Talley Bowden – Is turbo cancer inevitable? How long after the vaccine is it safe to donate blood or organs, as well as have sexual relations? Is methylene blue really safe? As the mRNA is synthetic, does this mean that we will never break down Pfizer or Moderna? Will all the vaccinated be dead within 10 years?

US equity-index futures dipped along with the dollar after President Donald Trump said he will set unilateral tariff rates within two weeks, dialing up trade tensions once again. The comments come a day after Chinese and US officials struck a positive tone following their talks to dial down trade tensions. Amid US talking with countries including India and Japan to lower the levies, some investors see Trump's comments as an effort to ramp up urgency in talks. We talk markets with Zachary Hill, Head of Portfolio Management at Horizon Investments. Plus - China's biotech industry is gaining momentum, with Pfizer and Bristol-Myers Squibb making billion-dollar deals with Chinese companies to license experimental cancer drugs. The industry is expected to continue growing, driven by factors such as US President Donald Trump's economic policies, cheaper and easier human testing in China, and an abundance of young and affordable engineering talent. We check in with Shuli Ren, Bloomberg Opinion Columnist, for a closer look at the sector.See omnystudio.com/listener for privacy information.

AUA2025: AUA Guidelines on Early Detection of Prostate Cancer: Maximizing Benefits, Minimizing Harm CME Available: https://auau.auanet.org/node/43021 At the conclusion of this activity, participants will be able to: 1. Apply the Early Detection of Prostate Cancer: AUA/SUO Guideline (2023), and understand the rationale, evidence, level of evidence, strength of recommendation and applications associated with each statement. 2. Maximize the benefits and minimize the harms of prostate cancer detection by carefully selecting patients and by using the necessary tools to detect clinically significant prostate cancer, while avoiding unnecessary biopsies and detection of clinically insignificant prostate cancers. 3. Describe the evidence supporting the use of PSA for early detection of prostate cancer, and apply that evidence to different clinical scenarios, incorporating patient characteristics and preferences. 4. Identify available blood, urine and tissue biomarkers used to enhance detection of higher-grade prostate cancer, the evidence supporting their use, and the clinical scenarios in which they are most valuable to be used. 5. Use MRI and fusion biopsy to enhance the detection of clinically significant prostate cancer and implement safe biopsy practices with respect to approach, avoidance of infection, and attention to patient comfort; understand the rationale for transperineal prostate biopsy and its technique; be able to establish a transperineal biopsy practice. ACKNOWLEDGEMENTS: This educational activity is supported by independent educational grants from: Astellas, Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC, Lantheus Medical Imaging, Novartis Pharmaceuticals Corporation, Pfizer, Inc.

Poderiam os vapores de uma fábrica deixar toda uma cidade animada DEMAIS? Se quem disputa a corrida é o seu fluido corporal, você pode ser considerado atleta? Esses e outros questionamentos com @katbarcelos e @odeiopepe no Vortex de hoje Acesse o link do Vortex e ganhe 15% de desconto na sua matrícula na Alura: https://www.alura.com.br/vortex ou CUPOM: VORTEX Desconto especial nos planos usando o nosso link no Nordvpn: https://nordvpn.com/vortexpod ou CUPOM: VORTEXPOD Host: Katiucha Barcelos. Instagram: @katbarcelos | Twitter/X: @katiucha Co-Host: Pedro Pinheiro. Instagram: @odeiopepe | Twitter/X: @OdeioPePe Nossas redes sociais: Instagram: @feedvortex Bluesky: @feedvortex.bsky.socia Twitter: @feedvortex Tiktok: @feedvortexReddit: r/feedvortex Grupo paralelo não-oficial do Vortex no telegram: https://t.me/+BHlkG92BfPU5Zjdh Esse grupo é dos ouvintes, para os ouvintes e pelos ouvintes. Não temos qualquer afiliação oficial ou responsabilidade por QUALQUER COISA falada neste grupo Link do post do episódio nas redes sociais: Instagram: https://www.instagram.com/p/DKxgUJjvYfV/?img_index=1 Twitter: https://x.com/feedvortex/status/1932895073886236723 Links comentados no episódio: Cidade irlandesa que fabrica Viagra se gaba de ter "vapores de amor" no ar Pfizer nega que vapores de fábrica de Viagra estejam excitando homens de cidade irlandesa Preferências femininas quanto ao tamanho do pênis: um novo método de pesquisa usando seleção entre modelos 3D Assisti a uma corrida de esperma com centenas de adolescentes. Foi uma merda total. Primeira vez na competição Narração da competição Prêmio menor, tamanho maior? Explorando o impacto do dinheiro nos marcadores de masculinidade autorrelatados pelos homens Produção: Thyara Castro, Bruno Azevedo e Aparecido Santos Edição: Joel Suke Ilustração da capa: Brann Sousa

In our second plenary episode, we're spotlighting two pivotal phase 3 trials: SERENA-6, which explores ctDNA-guided treatment with camizestrant to delay progression in HR-positive, HER2-negative advanced breast cancer with ESR1 mutations, and NIVOPOSTOP, a landmark study showing improved disease-free survival with adjuvant nivolumab in high-risk, resected head and neck squamous cell carcinoma. Join us as we unpack these practice-changing findings with expert insight and a couple of dad jokes along the way.Studies discussed in the episode:SERENA-6NIVOPOSTOPFor more episodes, resources and blog posts, visit www.inquisitiveonc.comPlease find us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of AlisiaBeats: https://pixabay.com/users/alisiabeats-39461785/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice.Oncology for the Inquisitive Mind is recorded with the support of education grants from our foundation partners Pfizer, Gilead Pharmaceuticals and Merck Pharmaceuticals. Our partners have access to the episode at the same time you do and have no editorial control over the content. Hosted on Acast. See acast.com/privacy for more information.

What if I told you that everything we believed about vaccine safety was built on manipulated data that pharmaceutical companies never wanted us to see? In this interview, I sat down with Dr. Aseem Malhotra, renowned British cardiologist, who reveals how independent analysis of Pfizer's original trial data showed you were more likely to suffer serious harm from the vaccine than be hospitalized with COVID at a rate of 1 in 800. Dr. Malhotra walks me through his co-founded Hope Accord petition signed by tens of thousands of medical professionals calling for a moratorium, how politicians were systematically misled, and why trust in medicine has plummeted to historic lows. Join my FREE 3-Day Ultimate Detox Challenge starting June 23rd.: ⁠https://bit.ly/3ZgCW4u⁠ Join the Ultimate Human VIP community today!: ⁠https://bit.ly/4ai0Xwg⁠ Connect with Dr. Aseem Malhotra: Website: ⁠https://bit.ly/4dCGKRZ⁠  YouTube: ⁠https://bit.ly/4jKLGal⁠  Instagram: ⁠https://bit.ly/4dFY2gY⁠  Facebook:⁠https://bit.ly/48ghD6F⁠  TikTok: ⁠https://bit.ly/4eZyHjr⁠  X.com: ⁠https://bit.ly/4eXnL5O⁠  Thank you to our partners: H2TABS - USE CODE “ULTIMATE10” FOR 10% OFF: ⁠https://bit.ly/4hMNdgg⁠ BODYHEALTH - USE CODE “ULTIMATE20” FOR 20% OFF: ⁠http://bit.ly/4e5IjsV⁠ BAJA GOLD - USE CODE "ULTIMATE10" FOR 10% OFF: ⁠https://bit.ly/3WSBqUa⁠ EIGHT SLEEP - SAVE $350 ON THE POD 4 ULTRA WITH CODE “GARY”: ⁠https://bit.ly/3WkLd6E⁠ COLD LIFE - THE ULTIMATE HUMAN PLUNGE: ⁠https://bit.ly/4eULUKp⁠ WHOOP - GET 1 FREE MONTH WHEN YOU JOIN!: ⁠https://bit.ly/3VQ0nzW⁠ MASA CHIPS - GET 20% OFF YOUR FIRST ORDER: ⁠https://bit.ly/40LVY4y⁠ VANDY - USE CODE “ULTIMATE20” FOR 20% OFF: ⁠https://bit.ly/49Qr7WE⁠ AION - USE CODE “ULTIMATE10” FOR 10% OFF: ⁠https://bit.ly/4h6KHAD⁠ HAPBEE - FEEL BETTER & PERFORM AT YOUR BEST: ⁠https://bit.ly/4a6glfo⁠ CARAWAY - USE CODE “ULTIMATE” FOR 10% OFF: ⁠https://bit.ly/3Q1VmkC⁠ HEALF - GET 10% OFF YOUR ORDER: ⁠https://bit.ly/41HJg6S⁠ BIOPTIMIZERS - USE CODE “ULTIMATE” FOR 10% OFF: ⁠https://bit.ly/4inFfd7⁠ RHO NUTRITION - USE CODE “ULTIMATE15” FOR 15% OFF: ⁠https://bit.ly/44fFza0⁠ GENETIC TEST: ⁠⁠https://bit.ly/3Yg1Uk9⁠ Connect with Gary Brecka: Instagram: ⁠https://bit.ly/3RPpnFs⁠ TikTok: ⁠https://bit.ly/4coJ8fo⁠ YouTube: ⁠⁠https://bit.ly/3RPQYX8⁠ X.com: ⁠https://bit.ly/3Opc8tf⁠ Facebook: ⁠https://bit.ly/464VA1H⁠ Website: ⁠https://bit.ly/4eLDbdU⁠ Merch: ⁠https://bit.ly/4aBpOM1⁠ Newsletter: ⁠https://bit.ly/47ejrws⁠ Timestamps: 00:00 ​Intro of Show 02:55 COVID-19 Vaccine Moratorium Petition Discussion 07:10 Historical vaccine withdrawals (swine flu, rotavirus) 09:40 COVID-19 Vaccine Moratorium Petition Current Status 20:11 Call for medical establishment apology & acknowledgment 24:52 Pharmaceutical manipulation vs. political misleading 29:31 Psychological barriers to accepting uncomfortable truths 34:19 Individual methylation differences and spike protein clearance 36:07 The realizations of the COVID propaganda campaigns 41:09 Treatment protocols for vaccine-injured patients 45:35 Framingham Study revelations 55:44 Dr. Malhotra's clinical approach to cholesterol management 01:00:15 Inflammation as root cause vs. cholesterol theory 01:09:16 Dr. Malhotra opinion on public health policy 01:17:48 ​What does it mean to you to be an Ultimate Human? The Ultimate Human with Gary Brecka Podcast is for general informational purposes only and does not constitute the practice of medicine, nursing or other professional health care services, including the giving of medical advice, and no doctor/patient relationship is formed. The use of information on this podcast or materials linked from this podcast is at the user's own risk. The Content of this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard or delay in obtaining medical advice for any medical condition they may have and should seek the assistance of their health care professionals for any such conditions. Learn more about your ad choices. Visit megaphone.fm/adchoices

The McCullough Report with Dr. Peter McCullough – Dr. Jeyanthi Kunadhasan's forensic analysis of Pfizer's COVID-19 vaccine trial exposes concealed deaths, buried autopsies, and delayed efficacy announcements ahead of the 2020 election. Findings challenge the FDA's emergency use authorization, highlighting data manipulation, missing follow-up, and severely compromised trial integrity in critical decision-making oversight...

The McCullough Report with Dr. Peter McCullough – Dr. Jeyanthi Kunadhasan's forensic analysis of Pfizer's COVID-19 vaccine trial exposes concealed deaths, buried autopsies, and delayed efficacy announcements ahead of the 2020 election. Findings challenge the FDA's emergency use authorization, highlighting data manipulation, missing follow-up, and severely compromised trial integrity in critical decision-making oversight...

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

In this episode of Molecule to Market, you'll go inside the outsourcing space of the global drug development sector with Angelo Gatto, CEO at Chanelle Pharma. Your host, Raman Sehgal, discusses the pharmaceutical and biotechnology supply chain with Angelo, covering: Why he chose to follow a big pharma divestment into the CDMO industry. The tricky transition from big pharma technical to commercial CDMO BD when he had the view of "I don't like sales people"! How commercial trust is developed through preparation, character and competences Why he couldn't resist the 'made for him' CEO role at Chanelle Pharma Making key strategic decisions to that make the business very attractive to a range of future buyers. The humanisation of animal care driving the pipeline and development of new products for small and large animals Angelo brings over 25 years of international experience in pharmaceuticals, in a career spanning animal health, human health and CDMO. He has held operations, commercial and management roles at Johnson & Johnson, AlfaSigma, Pfizer, Aenova Group, Adragos Pharma.  Since July 2024 is the CEO of Chanelle Pharma, Before joining Chanelle he also created a boutique advisory firm that has helped companies in last years to succeed in M&A deals and value creation, mostly in the CDMO space. Please subscribe, tell your industry colleagues and join us in celebrating and promoting the value and importance of the global life science outsourcing space. We'd also appreciate a positive rating! Molecule to Market is also sponsored and funded by ramarketing, an international marketing, design, digital and content agency helping companies differentiate, get noticed and grow in life sciences.  

Did you know Americans now spend over $400 billion a year on prescriptions—yet chronic disease is only rising? In this episode, Dr. Josh Axe uncovers the hidden history and ongoing influence of Big Pharma, revealing how natural medicine was pushed aside—and what you can do to reclaim your health. How the Flexner Report and Rockefeller shaped a drug-first medical system. Why 69% of U.S. adults take at least one medication—and 25% take four or more. The financial and political power of pharma giants, from Fauci to Pfizer. Why so many “diagnoses” today are just symptoms of a deeper imbalance. How the food system feeds illness—and pharma profits from the fallout. The root-cause tools of functional medicine that actually promote healing. Tune in to discover the truth about pharmaceuticals, the future of functional medicine, and how you can support your body naturally—without relying on daily prescriptions. #RootCauseHealing #BigPharmaExposed #FunctionalMedicine ------  Want more of The Dr. Josh Axe Show? Subscribe to the YouTube channel. Follow Dr. Josh Axe Instagram Twitter Facebook TikTok Website ------  Staying healthy in today's world is an upstream battle. Subscribe to Wellness Weekly, your 5-minute dose of sound health advice to help you grow physically, mentally, and spiritually. Every Wednesday, you'll get:  Holistic health news & life-hacks from a biblical world view Powerful free resources including classes, Q&As, and guides from Dr. Axe The latest episodes of The Dr. Josh Axe Show Submit your questions via voice memo to be featured on the show → speakpipe.com/drjoshaxe  ------  Links:  https://pmc.ncbi.nlm.nih.gov/articles/PMC3178858/ https://www.consumerreports.org/prescription-drugs/too-many-meds-americas-love-affair-with-prescription-medication/ https://www.statista.com/outlook/hmo/pharmaceuticals/worldwide https://www.biospace.com/u-s-pharmaceutical-market-size-to-reach-usd-1-093-79-billion-by-2033 https://www.hrsa.gov/opa/updates/2023-340b-covered-entity-purchases https://www.npr.org/2025/04/24/nx-s1-5374372/millions-of-american-kids-have-an-adhd-diagnosis-is-their-treatment-effective https://www.cnn.com/2023/04/18/health/teen-misuse-adhd-meds-wellness/index.html https://www.cdc.gov/nchs/products/databriefs/db388.htm https://www.aafp.org/pubs/afp/issues/2019/1215/p742.html https://pmc.ncbi.nlm.nih.gov/articles/PMC4859526/ https://www.ncbi.nlm.nih.gov/books/NBK532953/ https://hpi.georgetown.edu/rxdrugs/ https://www.cdc.gov/nchs/products/databriefs/db347.htm https://www.ncbi.nlm.nih.gov/books/NBK430655/ https://www.investopedia.com/articles/stocks/09/corporate-kleptocracy-rjr-nabisco.asp https://www.cdc.gov/museum/pdf/cdcm-pha-stem-uncovering-the-opioid-epidemic-lesson.pdf https://pmc.ncbi.nlm.nih.gov/articles/PMC2034715/ https://www.healthaffairs.org/doi/10.1377/hlthaff.2023.00418 https://www.nami.org/advocacy/policy-priorities/improving-health/mental-health-in-schools/ https://www.cms.gov/priorities/key-initiatives/open-payments https://pmc.ncbi.nlm.nih.gov/articles/PMC3778453/ https://www.pharmavoice.com/news/big-pharma-campaign-election-pac-donations/731124/ https://www.fiercepharma.com/pharma/fda-blocks-biopharma-employees-serving-advisory-committees https://pmc.ncbi.nlm.nih.gov/articles/PMC10830426/ https://weillcornell.org/news/america%E2%80%99s-loneliness-epidemic-what-is-to-be-done ------  Ads:  Even if your bloodwork looks "normal," your symptoms could point to Cell Danger Response (CDR). Discover how to break free from CDR and unlock your full potential at https://beyondbloodwork.com/

On this week's episode, John and Ken sit down with renowned cardiologist and health freedom advocate Dr. Peter McCullough to pull back the curtain on what he calls the “greatest medical cover-up of our time.” From suppressed FDA warnings and Pfizer's hidden myocarditis data to controversial Senate hearings and the media's erasure of scientific dissent, Dr. McCullough delivers a no-holds-barred account of COVID shot injuries, shedding, fertility concerns, and government corruption. He shares his bold calls to pull the vaccines from the market, his ongoing detox protocols, and what it means to fight for truth in the face of systemic silence.

In this dynamic episode, Meredith joins us to discuss how to create presentations that resonate deeply with your audience. Discover her expert tips on simplifying complex ideas, leveraging storytelling to inspire action, and ensuring your message stands out—whether you're presenting on stage, in meetings, or on camera.Meridith Grundei is a dynamic public speaking coach and innovative experience architect dedicated to helping leaders and entrepreneurs transform complex ideas into compelling, memorable presentations. Drawing from her extensive background in theater and improv, Meridith uniquely combines creativity, clarity, and authentic connection to empower clients to confidently command the stage and inspire action.As the founder of Grundei Coaching, Meridith has partnered with global industry leaders such as Google, Merck, Amazon AWS, and Pfizer, alongside numerous visionary entrepreneurs and professional teams. Renowned for her engaging, collaborative style, Meridith has successfully guided thousands of professionals to deliver impactful presentations, build meaningful connections, and elevate their overall communication effectiveness.Meredith also reveals how incorporating improvisation techniques into your training sessions can enhance your ability to think quickly, build genuine connections, and communicate with confidence and authenticity.Creativity isn't confined to artistic pursuits—it's transformative in business, driving innovation, problem-solving, and impactful communication. Whether you're an experienced speaker or new to presenting, this conversation equips you with powerful tools to express yourself clearly, creatively, and memorably.Connect with Meridith:https://www.linkedin.com/in/meridith/https://members.confidentlyspeaking.fun/Learn more about our Lyrics 'N Leadership Institute launch which is today May 28th, 2025 here: https://lyricsnleadership.org/   Listen to more episodes on Mission Matters:https://missionmatters.com/author/genein-letford/

AUA2025: Genetics and Genomics of Urological Cancers - Current Guidelines and Case-based Discussion to Guide Clinical Practice CME Available: https://auau.auanet.org/node/43015 At the conclusion of this activity, participants will be able to: 1. Describe key components of genetic risk assessment, genetic counseling, and informed consent for genetic testing. 2. Describe elements of genetic test reports including variant classification, variant allele frequency, gene penetrance, biomarkers, and clinical actionability. 3. Identify criteria for genetic testing for men with prostate cancer. Understand the clinical implications of genetic results in prostate cancer screening and management of both localized and advanced prostate cancer. 4. Describe genetic causes, clinical manifestations, indication for genetic testing, and cancer risk associated with hereditary kidney cancer syndromes. Understand how genetic mutation can guide targeted therapy in patients with von Hippel-Lindau syndrome. 5. Recognize genetic causes, tumor features, and cancer risk associated with Lynch syndrome and apply gained knowledge to improve care of patients with upper tract urothelial carcinoma. ACKNOWLEDGEMENTS: This educational activity is supported by independent educational grants from: Astellas, Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC, Lantheus Medical Imaging, Novartis Pharmaceuticals Corporation, Pfizer, Inc.

No vaccine development was ever more high-profile, or more fast-tracked, than the race to create a Covid shot in 2020. But then, two weeks before the 2020 election, Pfizer hit the pause button. Alex Berenson explains how the trail of evidence makes it clear that Pfizer and health authorities deliberately slowed down to deny Donald Trump a victory and help knock him out of office. Plus, CA gubernatorial candidate Steve Hilton reacts to Gavin Newsom's attempt to "cut the baby in half" on the biological men in women's sports. Watch every episode ad-free on members.charliekirk.com! Get new merch at charliekirkstore.com!Support the show: http://www.charliekirk.com/supportSee omnystudio.com/listener for privacy information.

No vaccine development was ever more high-profile, or more fast-tracked, than the race to create a Covid shot in 2020. But then, two weeks before the 2020 election, Pfizer hit the pause button. Alex Berenson explains how the trail of evidence makes it clear that Pfizer and health authorities deliberately slowed down to deny Donald Trump a victory and help knock him out of office. Plus, CA gubernatorial candidate Steve Hilton reacts to Gavin Newsom's attempt to "cut the baby in half" on the biological men in women's sports. Watch every episode ad-free on members.charliekirk.com! Get new merch at charliekirkstore.com!Support the show: http://www.charliekirk.com/supportSee omnystudio.com/listener for privacy information.

On this June 2nd edition of Badlands Daily, CannCon and Zak “RedPill78” Paine tackle the explosive aftermath of Trump's conviction, dissecting the political theater, legal irregularities, and public backlash rippling across the country. They discuss AG Ken Paxton's escalating legal moves against Pfizer and Big Pharma, explore the potential fallout of Fauci's congressional hearings, and analyze the media's shifting tone as they try to maintain the crumbling narrative. From voter disillusionment and election integrity to psyops and the DeSantis factor, the hosts connect the dots on how the deep state is losing control. They also spotlight Trump's renewed rally presence, his influence on black and Hispanic voters, and signs of grassroots momentum in swing states. With humor, righteous anger, and sharp analysis, this episode paints a clear picture: the storm is here, and the establishment is scrambling.

We begin with the HHS announcement that Covid shots will no longer be recommended to healthy children and pregnant women. What does healthy mean? And what are the conditions that provide release from liability for vaccine makers? Then, a discussion of kinds of immunity, and how vaccines are best delivered depending on how disease is transmitted. We compare what was claimed about the shots (they stop transmission!), and what Pfizer later admitted (that they did not know if the shots stopped transmission—but they had to move at the “speed of science”!). Also, a discussion of how to kill your pathogens by crossing ecological borders…and how to get rid of a botfly with a steak, or with ivermectin. Then: why are young male capuchin monkeys abducting baby howler monkeys on an island off the coast of Panama? Finally: a discussion of transhumanism, our future, our embodied selves, how we live on, what we owe our children, what our beloved dead would make of now, and how we, and the LLMs, could know.*****Our sponsors:Brain.fm: intense music that boosts productivity. Unlock your brain's full potential free for 30 days by going to http://brain.fm/DARKHORSEPique's Nandaka: delicious mushroom, tea, and chocolate drink that provides all day energy. Get 20% off plus free frother+beaker at http://www.Piquelife.com/DARKHORSEJolie: Beautiful showerheads that filter out the garbage without reducing water pressure. Go to http://jolieskinco.com/DarkHorse to get free shipping; free returns within 60 days.*****Join us on Locals! Get access to our Discord server, exclusive live streams, live chats for all streams, and early access to many podcasts: https://darkhorse.locals.comHeather's newsletter, Natural Selections (subscribe to get free weekly essays in your inbox): https://naturalselections.substack.comOur book, A Hunter-Gatherer's Guide to the 21st Century, is available everywhere books are sold, including from Amazon: https://amzn.to/3AGANGg (commission earned)Check out our store! Epic tabby, digital book burning, saddle up the dire wolves, and more: https://darkhorsestore.org*****Mentioned in this episode:Kennedy, Bhattacharya and Makary on changing vax recommendations: https://x.com/SecKennedy/status/1927368440811008138Dr. Lon Jones on mucosal immunity (on DHP): https://www.youtube.com/watch?v=w99CQVaOK0ERob Roos forcing truth from Pfizer: https://x.com/Rob_Roos/status/1579759795225198593Heather on killing your pathogens: https://open.substack.com/pub/naturalselections/p/kill-your-pathogensForrest Maready on polio (on DHP): https://www.youtube.com/watch?v=L7wYUnQUESUGoldsborough et al 2025. Rise and spread of a social tradition of interspecies abduction. Current Biology 35(10): R375-R376: https://www.cell.com/current-biology/fulltext/S0960-9822(25)00372-0Bret on transhumanism: https://x.com/BretWeinstein/status/1927043640813138102Support the show

The McCullough Report with Dr. Peter McCullough – People are asking if the synthetic mRNA products could have permanently altered them. Reverse transcription, a process used by retroviruses and certain other organisms, converts mRNA into a DNA copy, which can then be integrated into the host's genome, creating a permanent DNA version of the viral genetic information...

The McCullough Report with Dr. Peter McCullough – People are asking if the synthetic mRNA products could have permanently altered them. Reverse transcription, a process used by retroviruses and certain other organisms, converts mRNA into a DNA copy, which can then be integrated into the host's genome, creating a permanent DNA version of the viral genetic information...

Meet my friends, Clay Travis and Buck Sexton! If you love Verdict, the Clay Travis and Buck Sexton Show might also be in your audio wheelhouse. Politics, news analysis, and some pop culture and comedy thrown in too. Here’s a sample episode recapping four Thursday takeaways. Give the guys a listen and then follow and subscribe wherever you get your podcasts: HERE The Big Coverup The hour opens with analysis of former President Donald Trump's trip to the Middle East, including his visit with U.S. troops in Qatar and ongoing diplomatic efforts to prevent a nuclear Iran without engaging in war. The hosts highlight the potential for Trump to achieve peace in the region, even speculating on his worthiness for a Nobel Peace Prize—despite media resistance. A major focus of this hour is the explosive revelations surrounding President Joe Biden’s cognitive decline. Clay and Buck dissect new reports suggesting Biden frequently forgot the names of his top advisors, including long-time aides like Jake Sullivan and Kate Bedingfield. They argue that this is not a recent development, but a long-standing issue that was deliberately concealed by the media and Democratic leadership. The hosts call it a “vast left-wing conspiracy” to hide Biden’s mental and physical health from the American public, comparing it to the media’s treatment of January 6 and demanding congressional hearings to investigate the cover-up. The discussion also touches on the implications of the 25th Amendment, questioning why it was never invoked despite clear signs of presidential incapacity. Clay and Buck criticize the mainstream media, particularly CNN and MSNBC, for their complicity and dishonesty, asserting that many journalists knowingly misled the public. They also question the role of Vice President Kamala Harris and First Lady Jill Biden in perpetuating the alleged deception. Did you buy the dip? The Stock Market’s recovery and falling gas prices — developments they claim are being ignored by left-leaning media outlets. They also tease breaking news about Rep. Jim Jordan’s investigation into Pfizer allegedly delaying COVID-19 vaccine trial results to influence the 2020 election, further fueling claims of widespread institutional manipulation. Trump is working on no war in the Middle East and no nuclear Iran Supreme Court Rulings Hour 2 of The Clay Travis and Buck Sexton Show delivers a high-energy, in-depth analysis of the latest political and legal developments shaping the 2024 election cycle and beyond. The hour opens with a discussion of explosive claims from OH Rep. Jim Jordan, who alleges that Pfizer executives may have deliberately withheld COVID-19 vaccine trial results before the 2020 election—potentially influencing the outcome. Clay and Buck connect this to broader concerns about election integrity, media manipulation, and the growing list of revelations surrounding the so-called “rig job” of 2020. A major focus of this hour is the Supreme Court’s oral arguments on two critical issues: the legality of President Trump’s executive order on birthright citizenship and the constitutionality of nationwide injunctions issued by federal district court judges. The hosts break down the legal complexities, emphasizing how a single lower court judge currently holds outsized power to block presidential actions nationwide—an imbalance that undermines the separation of powers. Justice Clarence Thomas’s remarks are highlighted to show how this practice only emerged in the 1960s and has since exploded, particularly in left-leaning circuits like the Ninth. Status vs. Wealth Trump’s speech to U.S. troops stationed in Qatar, where he emphasized military strength, patriotism, and announced substantial pay raises for service members. Clay and Buck highlight the Trump administration’s success in revitalizing military recruitment and shifting the Pentagon’s focus back to national defense rather than progressive social agendas. The hosts then pivot to Trump’s diplomatic breakthroughs in the Middle East, including potential normalization with Syria and ongoing negotiations with Saudi Arabia, the UAE, Qatar, and even Iran. They underscore how Trump’s foreign policy is isolating Iran while strengthening U.S. alliances—moves that even some Democrats are quietly praising. On the economic front, Clay and Buck analyze new data showing falling gas prices, stable inflation, and strong retail sales, debunking fears that Trump’s tariffs would trigger a recession. They argue that the mainstream media’s silence on positive economic indicators—especially the dramatic drop in gas prices—reveals a clear bias. The hosts emphasize how lower energy costs are weakening adversaries like Russia and Iran while benefiting everyday Americans. The conversation then shifts to a broader discussion of American prosperity, with Buck explaining how the U.S. economy remains the most powerful wealth-generation engine in history. They contrast Trump’s pro-growth, pro-business policies with the Democrats’ obsession with regulation, wealth redistribution, and status-driven politics. Clay adds that even the poorest Americans enjoy a higher standard of living than most people globally, citing data that Mississippi is wealthier per capita than the UK. Make sure you never miss a second of the show by subscribing to the Clay Travis and Buck Sexton show podcast wherever you get your podcasts: ihr.fm/3InlkL8 For the latest updates from Clay and Buck: https://www.clayandbuck.com/ Connect with Clay Travis and Buck Sexton on Social Media: X - https://x.com/clayandbuck FB - https://www.facebook.com/ClayandBuck/ IG - https://www.instagram.com/clayandbuck/ YouTube - https://www.youtube.com/c/clayandbuck Rumble - https://rumble.com/c/ClayandBuck TikTok - https://www.tiktok.com/@clayandbuck YouTube: https://www.youtube.com/@VerdictwithTedCruzSee omnystudio.com/listener for privacy information.