Podcasts about Keynote

I wanted to share something really personal with you—my keynote presentation from the AWHONN Convention in Orlando, FL. In this talk, I open up about two moments that completely changed my life: being banned from donating blood in nursing school for being gay, and having my first panic attack after a long shift in the ICU.These moments could've broken me. But instead, they lit a fire. One pushed me to start Banned4Life and help lift the FDA's gay blood ban. The other led me to create my Nurse Blake social media accounts as a way to share my story & overcome burnout. Life gives us moments—some beautiful, some painful, some totally unexpected. My hope is that as you listen, you'll look at your own defining moments and realize: they don't have to hold you back. You have the power to take them, shape them, and turn them into something meaningful.___________I hope to see you later this Fall during my But Did You Die? Comedy Tour! Tickets on sale now at: nurseblake.com ___________I want to shoutout AWHONN for selecting me to be their Keynote and to everyone who attended my session!

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

We catch up with Keynote speaker: Professor Jill ZwickerDCD and ADHD keynote: How do developmental coordination disorder and ADHD intersect, and what are the implications for diagnosis and treatment?Join us for another brilliant conversation with a brilliant researcher - live from the EACD / IAACD Conference 2025, in Heidelberg Germany!

We catch up with Keynote speaker: Professor Tobias Banaschewski!Long-term impact of early life adversity on antisocial brain: What have been the most significant findings from your research on the long-term impact of early life adversity on the brain, particularly in relation to antisocial behaviour?Another brilliant interview with researchers from EACD / IAACD 2025 at Heidelberg Germany!

Thom Crosby is the CEO of Pal's Sudden Service, HQ'd in Kingstwon, TN. Pal's Sudden Service was first opened in 1956 in Kingstown, TN. Thom came on board in 1981 to help them grow. Thom's experience prior to Pal's was in corporate McDonald's and corporate Long John Silvers, as well as a franchisee with Wendy's. Today Thom is the CEO of Pal's and the company has 31 locations. All but 2 Pal's locations are drive-thru only.  Thom is a true believer and member of McClaskey Excellence Institute. David McClaskey was featured on the podcast, episode 1182, and you can learn more about him and his company here: https://www.restaurantunstoppable.com/mcclaskey-institute Join the Restaurant Unstoppable Network TODAY! Restaurant Unstoppable - EVOLVE! - Eric of Restaurant Unstoppable is now taking consultation and coaching calls! Book a consultation today! Schedule your call to become UNSTOPPABLE! Check out the website for more details: https://www.restaurantunstoppable.com/evolve Today's sponsors: Franchise Law Solutions - Thinking about franchising your restaurant? Success doesn't have to mean 100 units overnight. With the right plan, you can build a profitable, local or regional franchise brand. The team at Internicola Law Firm — franchise lawyers and franchise development experts — will show you how.  Visit www.franchiselawsolutions.com. US Foods: US Foods is hosting the event of the year, Food Fanatics 2025. August 19-20, 2025, at the Mandalay Bay, Las Vegas, NV. Network with over 5,000 Industry peers. Attend Zouk nightclub reception, expert breakout sessions, Keynote speeches, musical performances, and dramatic demonstrations, and sample the latest on-trend dishes. The Clock Is Ticking! Be Ready to Register on April 16 for Food Fanatics® 2025. To learn more, visit www.usfoods.com/foodfanatics2025 Restaurant Systems Pro - Join the 60-day Restaurant Systems Pro FREE TRAINING. This is something that has never been done before. This 60-day event is at no cost to you, but it is not for everyone. Fred Langley, CEO of Restaurant Systems Pro, will lead a group of restaurateurs through the Restaurant Systems Pro software and set up the systems for your restaurant. During the 60 days, Fred will walk you through the Restaurant Systems Pro Process and help you crush the following goals: Recipe Costing Cards; Guidance in your books for accounting; Cash controls; Sales Forecasting(With Accuracy); Checklists; Budgeting for the entire year; Scheduling for profit; More butts in seats and more… Click Here to learn more.  Let's make 2025 the year your restaurant thrives. Today's guest recommends: McClaskey Excellence Institute Guest contact info:  Website: https://www.palsweb.com/ Email: thom@palsweb.com Thanks for listening! Rate the podcast, subscribe, and share!  We are on Youtube: @RestaurantUnstoppable

June 26, 2025: Michael Han, MD, Enterprise CMIO and VP of MultiCare Health System, discusses his transition from the operating room to the boardroom. He argues that the path forward isn't through automating clinical decisions, but through revolutionizing call centers, scheduling, prior authorizations, and referrals. Michael reveals how ambient clinical documentation must evolve beyond simple note-taking into a treasure trove of unstructured data that can drive actions across the entire care continuum—from pre-visit chart preparation to post-visit care coordination. The conversation explores how leaders establish credibility as they transition from the operating room to the boardroom. Key Points: 02:43 Impact of Ambient Clinical Documentation 05:51 AI and Large Language Models in Healthcare 10:27 The Role of CMIO in Digital Transformation 15:05 Leadership and Credibility in Healthcare 24:51 Speed Round: Personal Insights X: This Week Health LinkedIn: This Week Health Donate: Alex's Lemonade Stand: Foundation for Childhood Cancer

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

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

Saifedean's keynote talk at the Bitcoin Conference, discussing whether Tether can save the dollar. Also included is an interview with Natalie Brunell at the conference.Enjoyed this episode? Join Saifedean's online learning platform to take part in weekly podcast seminars, access Saifedean's four online economics courses, and read his writing, including his new book, Principles of Economics! Find out more on Saifedean.com!The Saif House - High quality cloth hardcover bitcoin books by Saifedean & more delivered worldwide, with 10% off for paying in bitcoin - TheSaifHouse.com

You didn't start your business to stay stuck. If you're ready to finally hit 6 or 7 figures WITHOUT burning out — book a call with our team → https://weddingproceo.com/applicationEver feel like no matter how hard you hustle, you just can't break past that $100K mark? Working every weekend, buried in client work, and still stuck? Wedding Pro, it's not your clients—it's how you're spending your time.In this keynote from the 2025 Wedding Pro CEO Summit, I'm breaking down exactly why you're stuck and how to start thinking (and acting) like the CEO of a 6- or 7-figure wedding business. Let's get you out of the weeds and calculate what your hour is really worth.✨ Need help delegating or calculating your CEO hourly rate? Check out Dan Martell's book “Buy Back Your Time” — it's required reading around here.The (FREE!)ASSUME Sales Training: 2x your wedding bookings in 30 days—step by step. Thousands of wedding pros have already used it to land more clients immediately! http://weddingproceo.com/freetrainingorg========================= EPISODE BLOG, LINKS & MORE:https://weddingproceo.com/why-your-wedding-business-stuck-at-100k/========================= Thank you for tuning in to this episode of the Wedding Pro CEO Podcast. If you find these strategies helpful, make sure to share this episode with your fellow wedding pros. And remember, in the world of weddings, it's all about building genuine relationships and showcasing your best work. Until next time, keep shining, CEOs!Heads up, friend! Some of the links I share may be affiliate links, which means I may earn a small commission if you decide to purchase—at no extra cost to you. I only recommend tools and resources I actually use and love, and that I believe will help you grow a profitable, sustainable business you're obsessed with.PLEASE SUPPORT THE PODCAST! LEAVE A REVIEW HERE: https://ratethispodcast.com/swdHave a question you'd like Brandee to answer? Ask here: http://bit.ly/3ZoqPmz=========================FREE TRAINING for Wedding Business OwnersTake the Wedding Pro CEO's free GAP assessmentSupport the showFREE TRAINING for Wedding Business Owners Take the Wedding Pro CEO's free GAP assessmentSupport the show

The European Commission launched its AI Continent Action Plan, signaling a commitment to a more proactive role in the global AI ecosystem.Join Cornell's Lutz Finger and Lucilla Sioli, Director of the European Commission's AI Office, as they explore the EU's bold and optimistic vision of becoming the “AI Continent.”From cutting-edge AI factories and gigafactories to trusted data spaces and talent development, this Keynote highlights how Europe is building a uniquely powerful AI ecosystem rooted in collaboration, excellence, and democratic values. Follow eCornell on Facebook, Instagram, LinkedIn, TikTok, and X.

If you're speaking on stages or even thinking about it, listen in for hot tips you won't find anywhere else. There's no better way than speaking to make a powerful impact on others while also building your business and evolving as a person. As today's guests demonstrate, the risk of sharing your message with the world comes with many rewards. In this episode, Deb has an engaging conversation with Lis Hoyte, an expert in coercive control, and Cathy Holt, a champion of women's leadership, who are both building their businesses through speaking on stages big and small. Whether you're an aspiring speaker or looking for inspiration, this episode offers valuable takeaways on leveraging your voice for change and success.Cathy Holt - https://cathyholt.com Lis Hoyte - www.lishoyte.com

AWE USA 2025 delivered on its promise of feeling spatial. Not only was the mantra XR is Going Mainstream, AWE founder Ori Inbar optimistically declared 2025 as the year of the Master Builder - passionate domain subject experts creating XR solutions for their community filling in diverse content gaps that are shifting the balance between big brands and dedicated niche audiences.  Today's show features clips from our favorite moments during AWE's day-one morning keynotes:Ori Inbar's Welcome Keynote - XR Is Going Mainstream! | AWE USA 2025Bringing AI and AR Into the Real World Through Spectacles | AWE USA 2025Project Aura & More: XREAL's Vision for the Present and Future of XR by Chi Xu | AWE USA 2025Excited about our 41st podcast episode! We're officially on the road to our 50th with a very special mystery guest scheduled for that occasion. Thanks for listening! Subscribe to Zero to Start on your favorite podcast platform. Follow our podcast page on LinkedIn!FEATURED LINKS:XREAL One Pro - early bird pricing until June 30th Zero to Start is now on YouTube! Our AWE playlist !The Shoes of AWE 2025CONNECT WITH SICILIANA:LinkedInsicilianatrevino.com

Think de-escalation is just for law enforcement? Think again.In this episode of Dancing in the Discomfort Zone, Anne Bonney chats with Drew Moldenhauer (https://drewthespeaker.com/)—former police officer, emotional intelligence advocate, and founder of Blue Ethos (https://blue-ethos.com/) —about the surprising science and strategy behind de-escalation, communication, and psychological safety at work.With over a decade of high-stakes experience, Drew brings powerful insights from the field into the boardroom. He explains how stress hijacks our brains (hello, amygdala!), how poor communication costs us productivity, and why “soft skills” like empathy and listening are actually power tools for leaders.You'll hear about:The “Eminem Theory” of de-escalation (yep, that Eminem)What's really going on in the brain during a heated momentWhy psychological safety isn't fluff—it's the foundation of innovation and trustCalm tone + open body language = 93% of successful communication.Whether you're dealing with team tension, delivering hard feedback, or managing through change, this episode delivers actionable tools to help you stay calm, lead smarter, and create a safer, more connected workplace.If you're ready to build trust, prevent blow-ups, and lead with more clarity and care—this one's for you.Want more from Drew?https://drewthespeaker.com/https://blue-ethos.com/linkedin.com/in/drewwmoldenhauerDrew Moldenhauer is an author, international speaker, business owner, and college professor, as well as the visionary force behind Blue Ethos Specialized Training, where he serves as Owner and Master Instructor. He empowers clients through his Keynote speech, "High Stakes Teamwork". With over 17 years in law enforcement, Drew delivers impactful presentations on active threat response, de-escalation and situational awareness. Drew Moldenhauer shapes the future of safety through leadership and commitment to education.

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

A plethora of recent updates: -Pembrolizumab (perioperative) in head & neck cancer (Keynote-689) -Prostate cancer updates on cabozantinib/atezolizumab (yes, really) and talazoparib -Pirtobrutinib improves PFS in CLL -Zanubrutinib has a new dosage form on the way -Another mitomycin product approved with "reverse thermal properties" -A new regimen for FL of tafasitamab/rituximab/lenalidomide -A comparison of the new ROS1-inhibitor, taltrectenib, compared to other 1st-line treatment options

June 19, 2025: In this webinar re-run Jill McCormick, Co-Founder and EVP of Design and Product Development at Pixel Health, and Daniel Small, Vice President of Digital Services at Hartford HealthCare, discuss the process of creating a world-class patient experience. The conversation explores Hartford HealthCare's bold approach to reimagining digital and physical spaces, where defining the experience vision precedes technology decisions. Through human-centered design methodologies, they navigate the complex challenges of aligning stakeholders, excavating outdated technologies, and creating a "digital campus" that extends care beyond facility walls.  Key Points: 02:55 Improving Patient and Provider Experiences 08:06 The Importance of Intentional Design 13:12 Aligning Vision and Technology 25:07 Human-Centered Design in Healthcare 43:36 Q&A and Final Thoughts X: This Week Health LinkedIn: This Week Health Donate: Alex's Lemonade Stand: Foundation for Childhood Cancer

Keynote presentation by Energy Expert and Author Peter Kelly-Detwiler addressing today's EV managed charging EV challenges and opportunities.

In dieser kraftvollen Keynote erzählt Nicole von ihrem Weg zur wahren Größe. Als Kind drehte sie sich im perfekten weißen Kleid durch die Diskothek ihrer Eltern, außen angepasst, innen jedoch voller Sehnsucht nach Freiheit. Erst der plötzliche Verlust ihrer Mutter bringt sie dazu, das Leben radikal zu hinterfragen. Heute inspiriert Nicole Frauen, sich von Erwartungen zu lösen und ihre wahre Größe zu leben. In ihrer Keynote zeigt Nicole fünf Schritte zur inneren Freiheit und entfacht den Mut, sich selbst und seine wahre Persönlichkeit zu leben. Diese Keynote lädt ein, dich mitreißen zu lassen von dieser Kraft und selbst in die eigene Größe zu treten.  ---------------------  Bereit deine wahre Größe zu entfalten? In einem kostenfreien Beratungsgespräch mit meinem Team erfährst du, wie ich dich als Mentor auf deiner ganz persönlichen Reise unterstützen kann. Kostenfreies Gespräch: t-beck.com/nicole  BESUCHE NICOLE AUF:  nicolewehn.de ---------------------  WARTELISTE KILLER KEYNOTE BOOTCAMP 2027: Bring deine Botschaft auf die Bühne und kreiere deine eigene Keynote:  tobias-beck.com/kkb ---------------------- ICH FREUE MICH ÜBER DEINEN BESUCH UND LIKE AUF

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.

For more information and support, visit us at our NEW WEBSITE! https://www.thecirsgroup.com This week, we are continuing our recap of the CIRSx 2025 conference! Today, we are focusing on the treatment talks: Understanding the Pitfalls of Tick Borne Testing with Christian Navarro Torres, PhD, CIRS Lab Finding the Tick-Borne Needle in the Haystack: Tick Borne Infections in CIRS Patients with Peg DiTulio, DNP, APRN Diagnosing Lyme and Co-infections: An Investigation of the Availability, Diversity and Validity of the Current Testing with Dr. Laura Varga, DAOM Air Oasis EdTalk with Brad Baxter, COO A Unifying Theory of Neurodegeneration with Dr. Dale Bredesen The Actinobacteria Reduction Study: Making Life Easier for the CIRS Community with Eric Dorninger, ND, LAc Brain Injury in CIRS: From Specific Causation to a Unique Transcriptomic Fingerprint in Parkinson's with Dr. Ritchie Shoemaker The Principles of Body Typing as a Critical Tool for CIRS Success with Erin Livers , BA, ICNT Evidence-based Diagnoses and Strategies for the CIRS Microbiome with Dr. Lacey Venazi For more information and support, visit us at our NEW WEBSITE! https://www.thecirsgroup.com TIMESTAMPS 00:00 Introduction and disclaimer 00:45 Tick-Borne testing insights by Dr. Christian Navarro-Torres, Dr. Peg DiTulio, Dr. Laura Varga 09:02 AirOasis ED Talk by Brad Baxter 11:19 Dr. Dale Bredesen's Keynote on Alzheimer's and Neurodegeneration 15:46 Actinobacteria Reduction Study by Dr. Eric Dorninger 18:20 Dr. Shoemaker's Talk on Parkinson's Research 20:45 Principles of Body Typing for Nutrition by Nutritionist Erin Livers 23:23 CIRS and the Gut Microbiome by Dr. Lacey Venazi 27:41 Conclusion and Additional Resources Helpful links/info: CIRSx website: https://www.cirsx.com/ Dr. Christian Navarro-Torres' website: https://www.cirslab.com/ Dr. Peg DiTulio's website: https://regenixhealing.com/ Dr. Laura Varga: https://www.instagram.com/thejupiterapproach/ or email her at TheJupiterApproach@gmail.com Air Oasis website: https://www.airoasis.com/ Dr. Dale Bredesen's website: https://www.apollohealthco.com/dr-bredesen/ The Flow Free game Jacie plays: https://www.bgames.com/game/flow-free-online/ Our last CIRSx recap episode: https://youtu.be/0aLD_1ixWXU?si=5-DxFVxgy7dleux3 Dr. Eric Dorninger's website: https://drdorninger.com/ Dr. Ritchie Shoemaker's website: https://www.survivingmold.com/ Erin Livers' website: https://foodasnourishment.com/ Dr. Abravanel's Body Type Diet and Lifetime Nutrition Plan: https://a.co/d/g6Z1bP7 Dr. Lacey Venazi's website: https://www.drlacey.org/ Order Jacie's book! The 30 Day Carnivore Bootcamp: https://a.co/d/7MgHrRs The CIRS Group: Support Community: https://thecirsgroup.com Instagram: https://www.instagram.com/thecirsgroup/ Find Jacie for carnivore, lifestyle and limbic resources: Jacie's book on the Carnivore diet!  https://a.co/d/8ZKCqz0 Instagram: https://www.instagram.com/ladycarnivory YouTube: https://www.youtube.com/@LadyCarnivory Blog: https://www.ladycarnivory.com/ Find Barbara for business/finance tips and coaching: Website: https://www.actlikebarbara.com/ Instagram: https://www.instagram.com/actlikebarbara/ YouTube: https://www.youtube.com/@actlikebarbara Jacie is a Shoemaker certified Proficiency Partner, NASM certified nutrition coach, author, and carnivore recipe developer determined to share the life changing information of carnivore and CIRS to anyone who will listen. Barbara is a business and fitness coach, CIRS and ADHD advocate, writer, speaker, and a big fan of health and freedom. Together, they co-founded The CIRS Group, an online support community to help people that are struggling with their CIRS diagnosis and treatment.

Dr. Luke Woods was the Keynote speaker at the Givens Foundation's annual conference conference,  Dr. Luke Wood returned to his alma mater, Sacramento State to become its ninth president on July 16th, 2023. A nationally renowned scholar on racial equity with a specific focus on early childhood education and community colleges. Dr. Wood has authored or co-authored 16 books and published nearly 200 articles, focusing on racial inequity in education. Dr. Woods' bold vision for the university includes 23 strategic action items, including the creation of the Nation's First Black Honors College, which welcomed its inaugural class of scholars in the fall of 2024. President Wood holds a bachelor's degree in Black history and Politics and a Master's degree in higher education leadership from Sacramento State and a master of Education in Early Childhood Education, and a doctorate in Educational Leadership and Policy Studies with a higher education concentration from Arizona State University. “From Resistance to Resilience: The Evolution of African American Reading,” was an extraordinary opportunity to champion literacy, cultural equity, and social justice. Held on June 3, 2025, this event was made possible through the generous support of the Minnesota Humanities Center.  

Dorene Discovers Key Note Suggestions (6/18/25) by 96.5 WKLH

In this episode of the HR Mixtape podcast, host Shari Simpson takes you behind the scenes of SHRM25—the world's largest HR conference—happening June 29 to July 2 in San Diego. Drawing from over 20 years in the HR profession and countless conferences, Shari delivers a real-talk survival guide for navigating SHRM25 like a pro. From how to prep for President Biden's keynote to what to pack (and what to leave behind), Shari shares practical advice, first-timer strategies, and unexpected tips that will help you get the most out of your time in San Diego. Whether you're attending for the first time or the tenth, this episode will help you show up prepared, confident, and ready to make the most of every minute. Plus, learn how you can participate in Paylocity's GIVES event to help pack 10,000 sensory break kits for United Way San Diego and eight local YMCA locations. Listener Takeaways:  • Discover what to pack, what to wear, and how to avoid rookie mistakes at SHRM25  • Learn how to build a smart, flexible daily schedule with room for recharge  • Get security tips for attending President Joe Biden's keynote session  • Hear Shari's favorite networking hacks and hidden session gems   Hit “Play” and take 20 minutes to feel fully prepared for SHRM25—because showing up ready is the first step to making it unforgettable. Guest(s): Solo episode featuring Shari Simpson, Host of HR Mixtape

June 17th, 2025 - We welcome back Brent Haynes to explain the Minnesota politician murders. Then we're joined again by Michael Hichborn of the Lepanto Institute to discuss the dissident "Association of United States Catholic Priests" and their promotion of a condemned theologian. Includes the full Aftershow conversation. TheStationOfTheCross.com/ACT  

Send us a textIn this episode of The MLO Project, Frazier and Michael recap their time at the TAG Conference in Atlanta—sharing big takeaways, personal reflections, and a few laughs along the way.From standout moments with speakers like Dr. Jordan Peterson and Braden Shaw to real conversations about what's working (and what's not) in the mortgage industry, this one's packed with insight. The hosts talk about why community and connection still matter more than ever, especially for new originators navigating today's market.Plus, don't miss the announcement of their upcoming AI webinar and the launch of The Green Zone Project—a book every LO should have in their arsenal.If you're serious about growth, this episode hits different.00:00 Introduction and Community Building02:30 AI Webinar Announcement and Insights05:33 The Green Zone Live Experience12:07 Takeaways from the TAG Event14:02 New Guard vs. Old Guard in Lending14:53 Braden Shaw's Keynote on Social Media Growth18:59 Valuable Insights from the Event21:28 The New Guard in Business22:52 Attracting Business vs. Chasing Agents24:48 Community and Networking at Events25:18 Mastering Communication: Lessons from Jordan Peterson29:29 Understanding Obsession vs. Ambition32:08 Shifting Focus in Social Interactions35:23 Looking Ahead: Future Plans and GrowthRegister for our AI Webinar.Join our HighLevel Facebook GroupTMP is presented by: Empower LOConnect with us at mloproject@empowerlo.comGet The Green Zone Project Book!

This episode is a recording of a public event held on Thursday, April 24 at the Hennepin County Library in downtown Minneapolis. For the first time since COVID, Global Minnesota hosted our Great Decisions foreign policy conference on the topic India's Rising Influence. The event offered critical context on an important region of the world just as tensions flared once again between India and its neighbor Pakistan. Thanks to the generous support of the Foreign Policy Association for making this event possible. This episode includes an introductory presentation by local Great Decisions Speaker and Princeton University analyst Ned Downie as well as the keynote presentation "India's Rising Star" by Dr. Satu Limaye, Vice President of the East-West Center.  He painted a picture of India on the ascendancy, highlighting India's key historical role in the global nonaligned movement and its current relationship with its neighbors China and Pakistan.

Garrett Reed is the CEO of Layne's Chicken Fingers. Garrett got his start in the real estate business right out of college as a site selector for Radio Shack in he 90s. By the early 2000s he had moved on to Starbucks where he served as Real Estate Director for the east and west coasts. In 2005 he started his own real estate business and in the mid-2010s he began the search to own a restaurant brand and/or franchise. He bought Layne's Chicken Fingers in 2017 and became CEO and Partner. Layne's began in 1994. There are 25 locations as of this recording (April of 2025) with plans to open a new location every month for the rest of the year.  Join the Restaurant Unstoppable Network TODAY! Restaurant Unstoppable - EVOLVE! - Eric of Restaurant Unstoppable is now taking consultation and coaching calls! Book a consultation today! Schedule your call to become UNSTOPPABLE! Check out the website for more details: https://www.restaurantunstoppable.com/evolve Today's sponsors: Franchise Law Solutions - Thinking about franchising your restaurant? Success doesn't have to mean 100 units overnight. With the right plan, you can build a profitable, local or regional franchise brand. The team at Internicola Law Firm — franchise lawyers and franchise development experts — will show you how.  Visit www.franchiselawsolutions.com. US Foods: US Foods is hosting the event of the year, Food Fanatics 2025. August 19-20, 2025, at the Mandalay Bay, Las Vegas, NV. Network with over 5,000 Industry peers. Attend Zouk nightclub reception, expert breakout sessions, Keynote speeches, musical performances, and dramatic demonstrations, and sample the latest on-trend dishes. The Clock Is Ticking! Be Ready to Register on April 16 for Food Fanatics® 2025. To learn more, visit www.usfoods.com/foodfanatics2025 Restaurant Systems Pro - Join the 60-day Restaurant Systems Pro FREE TRAINING. This is something that has never been done before. This 60-day event is at no cost to you, but it is not for everyone. Fred Langley, CEO of Restaurant Systems Pro, will lead a group of restaurateurs through the Restaurant Systems Pro software and set up the systems for your restaurant. During the 60 days, Fred will walk you through the Restaurant Systems Pro Process and help you crush the following goals: Recipe Costing Cards; Guidance in your books for accounting; Cash controls; Sales Forecasting(With Accuracy); Checklists; Budgeting for the entire year; Scheduling for profit; More butts in seats and more… Click Here to learn more.  Let's make 2025 the year your restaurant thrives. Guest contact info:  Website: https://www.layneschickenfingers.com Thanks for listening! Rate the podcast, subscribe, and share!  We are on Youtube: @RestaurantUnstoppable

Each year the Rosales sisters host a fundraising gala to provide first-generation and immigrant students scholarships. This year I had the pleasure to be their keynote speaker.My keynote focused on the power community support, seeing potential in others, and smashing prejudice.To learn more about the Rosales Sister's organization, visit https://www.rsscholarship.com/Visit Aspira Consulting's website for information about our culturally relevant Career Readiness ProgramsWatch our YouTube channel for career and leadership tipsSubscribe to our e-newsletter to receive no BS career and leaderships tips in your in-box

About This Series Over six weeks, we're sharing keynote talks and discussions from the second Future Church Conference, held at the Tram Sheds in Glebe. This gathering brought together church leaders, pastors, and Jesus-followers passionate about creating safer, more inclusive faith communities.Whether you're leading church, leaving church, unsure about the whole thing, or just curious about what the future might hold, these conversations explore what it means to reimagine church for everyone.Conference Posture Future Church Conference invited participants to adopt three key postures:Lean in - Sit with discomfort and ask why certain ideas trigger usListen - Hear vulnerable ideas from speakers and connect with each otherLook forward - Focus on future possibilities rather than past woundsWhat You'll Hear in This Episode: Radhika Sukumar-White explores what it means for the church to actively work against racism and create genuinely diverse communities.About the Speaker: Radhika Sukumar-White is a Minister of the Word at Leichardt Uniting Church, and a friend of the Spiritual Misfits pod! Go back and listen to this earlier episode with her to hear more of Radhika's story and reflections: https://www.buzzsprout.com/1925719/episodes/13938060Want to reach out and let us know your thoughts or suggestions for the show? Send us a message here; we'd love to hear from you.The Spiritual Misfits Survival Guide (FREE): https://www.spiritualmisfits.com.au/survivalguideSign up to our mailing list:https://spiritualmisfits.com.au/Join our online Facebook community: https://www.facebook.com/groups/spiritualmisfitspodcastSupport the pod:https://spiritualmisfits.com.au/support-us/View all episodes at: https://spiritualmisfits.buzzsprout.com

I gave this keynote at the NAC Success Resources event in 2019 — and I went deep on the real shit that holds people back. It's not lack of resources. It's not bad luck. It's entitlement, insecurity, and the need to impress others instead of doing what actually makes you happy.If you've ever felt like you're stuck or not moving fast enough, this episode is a wake-up call. I break down the 5 core pieces of value that I believe will unlock your path to success — and most of them have nothing to do with business tactics and everything to do with mindset.Whether you're just starting or scaling, this talk will push you to get brutally honest with yourself and start executing.

Apple's Worldwide Developers Conference is always the first glimpse at what we can look forward to with new Apple software, including a peek at the photo capabilities of the next iPhones. And with iOS 26 and the Liquid Glass interface, things are going to look a lot different in the fall. Hosts: Jeff Carlson: website (https://jeffcarlson.com), Jeff's photos (https://jeffcarlson.com/portfolio/), Jeff on Instagram (http://instagram.com/jeffcarlson), Jeff on Glass (https://glass.photo/jeff-carlson), Jeff on Mastodon (https://twit.social/@jeffcarlson), Jeff on Bluesky (https://bsky.app/profile/jeffcarlson.bsky.social) Kirk McElhearn: website (https://www.kirkville.com), Kirk's photos (https://photos.kirkville.com), Kirk on Instagram (https://instagram.com/mcelhearn), Kirk on Glass (https://glass.photo/mcelhearn), Kirk on Mastodon (https://journa.host/@mcelhearn), Kirk on Bluesky (https://bsky.app/profile/kirkville.com) Show Notes: (View show notes with images at PhotoActive.co (https://www.photoactive.co/home/episode-188-wwdc25)) Rate and Review the PhotoActive Podcast! (https://itunes.apple.com/us/podcast/photoactive/id1391697658?mt=2) WWDC 2025 Keynote (https://developer.apple.com/videos/play/wwdc2025/101/) The Illusion of Thinking: Understanding the Strengths and Limitations of Reasoning Models via the Lens of Problem Complexity (https://machinelearning.apple.com/research/illusion-of-thinking) Subscribe to the PhotoActive podcast newsletter at the bottom of any page at the PhotoActive web site (https://photoactive.co) to be notified of new episodes and be eligible for occasional giveaways. If you've already subscribed, you're automatically entered. If you like the show, please subscribe in iTunes/Apple Podcasts (https://itunes.apple.com/us/podcast/photoactive/id1391697658?mt=2) or your favorite podcast app, and please rate the podcast. And don't forget to join the PhotoActive Facebook group (https://www.facebook.com/groups/photoactivecast/) to discuss the podcast, share your photos, and more. Disclosure: Sometimes we use affiliate links for products, in which we receive small commissions to help support PhotoActive.

Michael Praver is the founder of fundingfundingfunding.com Michael's company specializes in helping businesses secure capital without the stress of traditional lending. Their mission is to help businesses secure fast, reliable, and customized funding solutions that empower businesses to thrive.  This workshop covers How To Get Funding with expert Michael Praver. Workshops can be found every Thursday in the Restaurant Unstoppable podcast feed or on YouTube. Most have a visual component, so consider watching the video version here. Join the RUNetwork to take part in workshops and ask the experts YOUR questions! Join the Restaurant Unstoppable Network TODAY! Restaurant Unstoppable - EVOLVE! - Eric of Restaurant Unstoppable is now taking consultation and coaching calls! Book a consultation today! Schedule your call to become UNSTOPPABLE! Check out the website for more details: https://www.restaurantunstoppable.com/evolve Today's sponsors: Franchise Law Solutions - Thinking about franchising your restaurant? Success doesn't have to mean 100 units overnight. With the right plan, you can build a profitable, local or regional franchise brand. The team at Internicola Law Firm — franchise lawyers and franchise development experts — will show you how.  Visit www.franchiselawsolutions.com. US Foods: US Foods is hosting the event of the year, Food Fanatics 2025. August 19-20, 2025, at the Mandalay Bay, Las Vegas, NV. Network with over 5,000 Industry peers. Attend Zouk nightclub reception, expert breakout sessions, Keynote speeches, musical performances, and dramatic demonstrations, and sample the latest on-trend dishes. The Clock Is Ticking! Be Ready to Register on April 16 for Food Fanatics® 2025. To learn more, visit www.usfoods.com/foodfanatics2025 Restaurant Systems Pro - Join the 60-day Restaurant Systems Pro FREE TRAINING. This is something that has never been done before. This 60-day event is at no cost to you, but it is not for everyone. Fred Langley, CEO of Restaurant Systems Pro, will lead a group of restaurateurs through the Restaurant Systems Pro software and set up the systems for your restaurant. During the 60 days, Fred will walk you through the Restaurant Systems Pro Process and help you crush the following goals: Recipe Costing Cards; Guidance in your books for accounting; Cash controls; Sales Forecasting(With Accuracy); Checklists; Budgeting for the entire year; Scheduling for profit; More butts in seats and more… Click Here to learn more.  Let's make 2025 the year your restaurant thrives. Guest contact info:  Website Thanks for listening! Rate the podcast, subscribe, and share!  We are on Youtube: @RestaurantUnstoppable

On this episode of the My Veterinary Life podcast, we are thrilled to welcome 2025 AVMA Convention keynote speaker, Megan Leavey. Megan is a former Marine Corps corporal and military police canine handler. She shares her journey from childhood animal lover to military service, where she bonded deeply with her canine partner, Rex. She recounts the challenges of adopting Rex post-service, highlighting the importance of community support. Megan's story transitions to her career in veterinary medicine, balancing motherhood, and her enduring passion for animals. Her narrative underscores perseverance, resilience, and the profound human-animal bond. We can't wait to share her journey with you.  Thank you to our podcast partner Hill's Pet Nutrition! You can find more information about Hill's Pet Nutrition at https://www.hillspet.com/ and https://www.hillsvet.com/.Remember we want to hear from you! Please be sure to subscribe to our feed on Apple Podcasts and leave us a rating and review. You can also contact us at MVLpodcast@avma.orgFollow us on social media @AVMAVets #MyVetLife #MVLPodcast

June 12, 2025: Jennifer Stemmler, Chief Digital and Information Officer at Adventist Health, opens up about orchestrating one of healthcare's largest EHR migrations—transitioning 28 hospitals and 400 clinics from a decades-old Cerner system to Epic. Guided by the mantra "on time, on budget, on Epic, on us," how does she maintain control without micromanaging every decision? When groups push back on standardization or value-based care teams clash with implementation timelines, what framework actually works to resolve conflicts? Jennifer reveals her benefits realization scorecard approach and discusses the real challenge behind any major transformation: how do you ensure the organization owns the change rather than waiting for someone else to save them? Key Points: 03:09 Strategic Planning and Key Objectives 06:25 Guiding Principles and Pre-Planning Phase 17:44 Managing Internal Tensions and Lessons Learned 25:56 Post-Go-Live Success and Future Planning 34:36 Final Thoughts and Advice for Other Health Systems X: This Week Health LinkedIn: This Week Health Donate: Alex's Lemonade Stand: Foundation for Childhood Cancer

Rich talks Identity at Tony Hoty's Lead Gen Expo 2025

The MacVoices Live! panel took on the task of analyzing Apple's WWDC 2025 keynote, focusing on meaningful updates across iPadOS, Vision Pro, macOS, and iOS. Discussions included the new Liquid Glass interface, cross-platform consistency, and practical enhancements driven by Apple Intelligence. Panelists Chuck Joiner, David Ginsbug, Brittany Smith, Marty Jencius, Ben Roethig, Jeff Gamet, Eric Bolden, and Brian Flanigan-Arthurs debated the usefulness of iPad improvements, praised the Preview app's arrival on more devices, and examined accessibility implications. Before all that, the group paid tribute to Bill Atkinson, recognizing his pivotal role in Apple's legacy.  Today's MacVoices is supported by CleanMyMac by MacPaw, your ultimate solution for Mac control and care. Try CleanMyMac for 7 days free, then use the code “MacVoices20” for 20% off at CLNMY.com/MacVoices. Show Notes: Chapters: 00:08 Introduction to WWDC 2025 Keynote 04:03 Remembering Bill Atkinson 06:55 Keynote Highlights Begin 09:55 iPad and Vision Pro Features 13:07 Unified Interface Across Devices 16:00 Apple Intelligence Discussion 18:15 Preview App Recognition 21:15 General Impressions of the Keynote 25:30 Liquid Glass Interface Explained 30:26 Accessibility Concerns with Liquid Glass Links: MacVoices #1019: MacVoices at Macworld – Bill Atkinson Shows Off His New PhotoCard iPhone App, and Comments on the iPad https://macvoices.com/macvoices-1019-macvoices-at-macworld-bill-atkinson-shows-off-his-new-photocard-iphone-app-and-comments-on-the-ipad/ MacVoices #1019: MacVoices at Macworld – Bill Atkinson Shows Off His New PhotoCard iPhone App, and Comments on the iPad https://www.youtube.com/watch?v=0_DjDdfqtUE Guests: Eric Bolden is into macOS, plants, sci-fi, food, and is a rural internet supporter. You can connect with him on Twitter, by email at embolden@mac.com, on Mastodon at @eabolden@techhub.social, on his blog, Trending At Work, and as co-host on The Vision ProFiles podcast. Brian Flanigan-Arthurs is an educator with a passion for providing results-driven, innovative learning strategies for all students, but particularly those who are at-risk. He is also a tech enthusiast who has a particular affinity for Apple since he first used the Apple IIGS as a student. You can contact Brian on twitter as @brian8944. He also recently opened a Mastodon account at @brian8944@mastodon.cloud. Jeff Gamet is a technology blogger, podcaster, author, and public speaker. Previously, he was The Mac Observer's Managing Editor, and the TextExpander Evangelist for Smile. He has presented at Macworld Expo, RSA Conference, several WordCamp events, along with many other conferences. You can find him on several podcasts such as The Mac Show, The Big Show, MacVoices, Mac OS Ken, This Week in iOS, and more. Jeff is easy to find on social media as @jgamet on Twitter and Instagram, jeffgamet on LinkedIn., @jgamet@mastodon.social on Mastodon, and on his YouTube Channel at YouTube.com/jgamet. David Ginsburg is the host of the weekly podcast In Touch With iOS where he discusses all things iOS, iPhone, iPad, Apple TV, Apple Watch, and related technologies. He is an IT professional supporting Mac, iOS and Windows users. Visit his YouTube channel at https://youtube.com/daveg65 and find and follow him on Twitter @daveg65 and on Mastodon at @daveg65@mastodon.cloud. Dr. Marty Jencius has been an Associate Professor of Counseling at Kent State University since 2000. He has over 120 publications in books, chapters, journal articles, and others, along with 200 podcasts related to counseling, counselor education, and faculty life. His technology interest led him to develop the counseling profession ‘firsts,' including listservs, a web-based peer-reviewed journal, The Journal of Technology in Counseling, teaching and conferencing in virtual worlds as the founder of Counselor Education in Second Life, and podcast founder/producer of CounselorAudioSource.net and ThePodTalk.net. Currently, he produces a podcast about counseling and life questions, the Circular Firing Squad, and digital video interviews with legacies capturing the history of the counseling field. This is also co-host of The Vision ProFiles podcast. Generally, Marty is chasing the newest tech trends, which explains his interest in A.I. for teaching, research, and productivity. Marty is an active presenter and past president of the NorthEast Ohio Apple Corp (NEOAC). Ben Roethig has been in the Apple Ecosystem since the System 7 Days. He is the a former Associate Editor with Geek Beat, Co-Founder of The Tech Hangout and Deconstruct and currently shares his thoughts on RoethigTech. Contact him on  Twitter and Mastodon. Brittany Smith is a trained cognitive neuroscientist who provides ADD/ADHD, technology, and productivity coaching through her business, Devise and Conquer, along with companion video courses for folks with ADHD. She's also the cofounder of The ADHD Guild, a community for nerdy folks with ADHD. She, herself, is a self-designated “well-rounded geek”. She can be found on Twitter as @addliberator, on Mastodon as @addliberator@pdx.social, and on YouTube with tech tips.   Support:      Become a MacVoices Patron on Patreon      http://patreon.com/macvoices      Enjoy this episode? Make a one-time donation with PayPal Connect:      Web:      http://macvoices.com      Twitter:      http://www.twitter.com/chuckjoiner      http://www.twitter.com/macvoices      Mastodon:      https://mastodon.cloud/@chuckjoiner      Facebook:      http://www.facebook.com/chuck.joiner      MacVoices Page on Facebook:      http://www.facebook.com/macvoices/      MacVoices Group on Facebook:      http://www.facebook.com/groups/macvoice      LinkedIn:      https://www.linkedin.com/in/chuckjoiner/      Instagram:      https://www.instagram.com/chuckjoiner/ Subscribe:      Audio in iTunes      Video in iTunes      Subscribe manually via iTunes or any podcatcher:      Audio: http://www.macvoices.com/rss/macvoicesrss      Video: http://www.macvoices.com/rss/macvoicesvideorss

Season 19, Episode 12 (#452) On this episode of For Mac Eyes Only: Mike is joined by Eric, Darren, and Dave and lead off the episode with a brief tribute to Macintosh pioneer Bill Atkinson who passed on June 5th, then dive in to the Keynote to provide their first-hand reactions* to Apple's WWDC 2025 […]

This week we react to all of the announcements from the WWDC 2025 Keynote. What were we excited about? What seemed not yet ready for prime time, or what we need to experience before getting excited!In this episode:Quiet mention of Apple IntelligenceNaming conventions: 26 (iOS 26, MacOS 26 "Tahoe", etc)Liquid Glass - do we like it?Phone app, spam screeningsLive translationsMusic App updatesWallet app - car Keys and digital IDWatch OS workout buddyMacOS Spotlight updatesNew Vision OS PersonasiPad OS multitaskingiPad local captureLet us know your thoughts! feedback@applevisionshow.com Hosted on Acast. See acast.com/privacy for more information.

In this podcast, The tech doctors discussed Apple's WWDC 2025 announcements, covering new features and updates across iOS, iPadOS, macOS, and watchOS platforms. They explored the introduction of AI advancements, accessibility improvements, and design changes like the “liquid glass” interface, as well as enhancements to various apps and services. The group shared their impressions and […]

Watch the WWDC25 keynote introducing our broadest design update ever and a more helpful Apple Intelligence. You'll also learn about exciting features coming with iOS 26, iPadOS 26, macOS 26, watchOS 26, visionOS 26, and tvOS 26.

Listen to the WWDC25 keynote introducing our broadest design update ever and a more helpful Apple Intelligence. You'll also learn about exciting features coming with iOS 26, iPadOS 26, macOS 26, watchOS 26, visionOS 26, and tvOS 26.

Apple kicked off its Worldwide Developers Conference this morning. WWDC is the event where developers are educated and the public is informed about all the new features coming to their various operating systems this fall. We discuss the announcements, what we're excited about, and what confuses us. Watch on YouTube! - Notnerd.com and Notpicks.com INTRO (00:00) Apple Intelligence (03:15) Liquid Glass (04:40) iOS 26 (10:40) WatchOS 26 (21:55) tvOS 26 (22:30) macOS 26, Tahoe (24:30) visionOS 26 (31:45) iPadOS 26 (34:55)

This week, we welcome Cornell Winston (current President of the American Association of Law Libraries) and Jenny Silbiger (President‑Elect). Speaking from sunny San Diego and O‘ahu's courthouse halls, the duo joins the show to preview AALL's 2025 Annual Meeting in Portland, Oregon—and to talk candidly about the challenges and opportunities facing the legal‑information profession during a time of rapid technological and political flux.Cornell and Jenny explain why open communication has become a strategic imperative for AALL. Although board books have long been public, they are doubling down on proactive updates—through e‑briefings, “Know‑It‑AALL” newsletters, and 80‑plus committee channels—because members crave clarity when the profession feels under siege. Their message is simple: phone numbers and inboxes are open; no question is off‑limits. The leaders frame transparency not as a defensive posture, but as an invitation to pull every member into the conversation and decision‑making process.The discussion then turns to the vacant Government Relations role—often seen as AALL's front line in Washington. Cornell reassures listeners that, despite the hiring gap, advocacy has never left the stage: the Government Relations Committee partners with ALA and other allies, tracks executive‑order whiplash, and issues public statements on IMLS funding or Library of Congress appointments. While lobby dynamics have shifted since COVID‑era restrictions, AALL continues to file comments, weigh amicus briefs, and equip members to speak up in their own jurisdictions until the position is refilled.Next, the hosts probe changes to the volunteer pipeline. Under the new process, virtually every member who raises a hand gets a seat—whether on a jury, committee, or the coveted Annual Meeting Program Committee. Headquarters now monitors overlapping appointments to spread opportunities and ensure early‑career librarians experience the career‑shaping mentorship Greg once received from the late Bob Oakley. Jenny underscores that engagement options range from micro‑tasks to multi‑year leadership roles, accommodating both time‑pressed newcomers and seasoned veterans.Turning to the July 19‑22 conference itself, Cornell shares upbeat registration numbers, hotel tips, and—importantly—news of no late‑registration fee increase. Portland's light‑rail pass, tax‑free shopping, and Nike/Columbia/Adidas discounts sweeten the trip, but the intellectual draw is formidable: 65‑plus programs, four pre‑conference workshops, and a cross‑pollinated AI track that unites academic and private‑sector librarians. Keynote speaker Roosevelt Weeks, renowned for transforming Austin Public Library into a nationally acclaimed, radically welcoming space, will challenge attendees to double down on access and inclusion.Asked for their “biggest challenge” predictions, Jenny cites the breakneck pace of AI and the resulting imperative to preserve integrity in an era of deepfakes and data deluge. Cornell echoes the warning: librarians must remain society's trusted validators and proclaim that expertise without apology. As the gavel passes in Portland, Jenny's presidential agenda crystallizes around three goals—meeting members where they are, converting dialogue into strategic action, and leaving the profession stronger for the next generation. Whether you are a long‑time AALL stalwart or a first‑time volunteer, this episode is a reminder that the future of legal information will be shaped by those who show up, speak up, and keep the channels open.Listen on mobile platforms:  ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Apple Podcasts⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ |  ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Spotify⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ | ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠YouTube⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠[Special Thanks to ⁠Legal Technology Hub⁠ for their sponsoring this episode.] Blue Sky: ⁠⁠@geeklawblog.com⁠⁠ ⁠⁠@marlgeb⁠⁠⁠⁠⁠⁠⁠Email: geekinreviewpodcast@gmail.comMusic: ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Jerry David DeCicca⁠⁠⁠⁠⁠⁠⁠⁠⁠ Transcript

Apple's WWDC is on the horizon. Tune in on June 9th at 10am Pacific Time and be the first to hear the latest announcements. You can also get a first look at the newest technologies coming to your favorite Apple devices.

Zack and Silvana Walters are the Owners/Partners at Sedalia's Oysters & Seafood located in Oklahoma City. Zack and Silvana are married and met in 2017. Prior to 2017, Zack went to culinary school and eventually opened his own butcher shop/deli in LA in 2010 with a partner which was very successful. He left that venture in 2016 to work in another restaurant where he met Silvana who worked FOH there. Silvana lived in NYC and worked FOH in various restaurants before loving to LA to work in an art museum and work restaurants. Silvana worked under Will Guidara before she met Zack. After meeting, the two left LA for OKC in 2020 and in 2022 they opened Sedalia's. Check out Grills by Demant (past guest on the show) as recommended by today's guest! Join the Restaurant Unstoppable Network TODAY! Restaurant Unstoppable - EVOLVE! - Eric of Restaurant Unstoppable is now taking consultation and coaching calls! Book a consultation today! Schedule your call to become UNSTOPPABLE! Check out the website for more details: https://www.restaurantunstoppable.com/evolve Today's sponsors: Franchise Law Solutions - Thinking about franchising your restaurant? Success doesn't have to mean 100 units overnight. With the right plan, you can build a profitable, local or regional franchise brand. The team at Internicola Law Firm — franchise lawyers and franchise development experts — will show you how.  Visit www.franchiselawsolutions.com. US Foods: US Foods is hosting the event of the year, Food Fanatics 2025. August 19-20, 2025, at the Mandalay Bay, Las Vegas, NV. Network with over 5,000 Industry peers. Attend Zouk nightclub reception, expert breakout sessions, Keynote speeches, musical performances, and dramatic demonstrations, and sample the latest on-trend dishes. The Clock Is Ticking! Be Ready to Register on April 16 for Food Fanatics® 2025. To learn more, visit www.usfoods.com/foodfanatics2025 Restaurant Systems Pro - Join the 60-day Restaurant Systems Pro FREE TRAINING. This is something that has never been done before. This 60-day event is at no cost to you, but it is not for everyone. Fred Langley, CEO of Restaurant Systems Pro, will lead a group of restaurateurs through the Restaurant Systems Pro software and set up the systems for your restaurant. During the 60 days, Fred will walk you through the Restaurant Systems Pro Process and help you crush the following goals: Recipe Costing Cards; Guidance in your books for accounting; Cash controls; Sales Forecasting(With Accuracy); Checklists; Budgeting for the entire year; Scheduling for profit; More butts in seats and more… Click Here to learn more.  Let's make 2025 the year your restaurant thrives. Today's guest recommends:  Grills by Demant Guest contact info:  Website: https://www.sedaliasokc.com Instagram: @sedaliasokc Email: info@sedaliasokc.com Thanks for listening! Rate the podcast, subscribe, and share!  We are on Youtube: @RestaurantUnstoppable

In this episode, Gary speaks to a group of business owners about the real challenges and opportunities in today's landscape — from the rapid evolution of AI to the often-overlooked power of consistent social content.He explains why many businesses aren't seeing results with digital marketing, how simple strategies like localized video ads can drive actual customer growth, and why understanding AI isn't just a competitive edge — it's quickly becoming a necessity.If you're navigating hiring issues, trying to stand out in a crowded market, or simply unsure where to start with new tools and platforms, this episode offers a clear, practical perspective.We cover:Common mistakes in social media marketing — and how to correct themA $50 local ad strategy that's working right nowWhy AI will impact every industry — not just techHow trust and authenticity will separate brands that grow from those that don'tTips for creating content without overthinking itWhether you're just starting to explore AI or trying to make your content actually move the needle, this conversation will help you rethink where to focus your time and energy in 2025.

Sometimes the smallest gesture creates the biggest return.In this episode, I talk about one of my favorite stories ever—where a simple act of gratitude turned into a massive business opportunity. This is for all the entrepreneurs out there who are obsessed with scale and tech... but might be sleeping on the old-school moves that really build brand equity.This isn't theory—it's a real case study of how doing the unscalable can scale your business better than any ad campaign. I also break down the mindset you need to win in today's economy: either go all in on social media or go all in on relationships. The middle? That's where businesses die.