GU ASCO 2026 Highlights – CREST, POTOMAC, EV-304/KEYNOTE-B15, LITESPARK-011/022, CAPITELLO-281

[MUSIC] We are the oncology brothers. >> Hello and welcome back to the oncology brothers podcast. I'm Rahul Gossane, here with my brother and co-host Rohit Gossane. We're excited to bring you key highlights from ASCO GU 2026 meeting which wrapped up just a few days ago. >> Right, Rahul. We saw some practice changing and some practice reinforcing studies at GUASCO 2026. What we are seeing from bladder cancer space, particularly from non-muscle invasive, where immunotherapy is making its way in early line where we are now combining that with BCG. For muscle invasive bladder cancer, we saw EV304, keynote B15, for ciseligable. Where now we are seeing that ciseligibility or ineligibility criteria fade away because we'll be using EV Pembro for everyone. In RCC, what we saw was BELZUDEFAN combination in adjuvant setting as well as in second line space for metastatic disease. And for prostate, we have some data around P10 loss. To walk us through this data in hand, it is always such a pleasure to have Dr. Petro's grievous in the house. A medical oncologist from the Fred Hudge Cancer Center. Petro, thanks so much for joining us. >> Rahul and Rohit, thank you so much for having me. All of us, such a great pleasure to see you and we're an amazing ASCO GU we saw a few days ago. >> Absolutely, exciting times. Petro's welcome. Petro's let's start with bladder cancer, where we have crest and Potomac studies and EV 304 study. Then in kidney cancer, we want to touch on light spark studies. And in prostate cancer, we have capitolot 281 trial. Let's start with non-muscle invasive bladder cancer. Historically, we had BCG. We saw some data around pretzelt therapy and then Pembro was a mag in refractory settings. Here at GU ASCO, we saw data from crest study looking at immunotherapy for two years. And earlier at ESMO, we saw data from Potomac looking at the valumap for one year, combined with BCG for high risk non-muscle invasive bladder cancer. Petro's, can you touch on these studies and they're fine things? >> It's interesting to see the data from actually three trials to your point. Potomac looking at the valumap, crest looking at the sassalimap, subcutanusly at the Minestate Checkpoint Hibitor. And the third trial was Alban, that was also presented at ESMO a few months ago. These trials apply to BCG naive, technically null deck, knows high risk non-muscle invasive bladder cancer. The somatic oncologists are not managing this disease, BCG naive, NMIBC. In these trials, the question was the systemic check potent inhibition addition does add value or not to the intraversical BCG, intraversical BCG, induction and maintenance, ideally for three years in high risk disease has been the start of care for many years. And of course, we all talk about the BCG short dodge, which is a major challenge here in the US and some other countries. So there have been efforts to try to build upon that and these trials looked at the, as I mentioned, the potential value of adding systemically administered checkpoint inhibition to intraversical BCG. Two trials were positive, Potomac and crest meeting their primary points. And Alban was negative, did not meet the primary point. And of course, their discussions about why Potomac and crest were positive while Alban was negative. And of course, there's some new unsend details that may potentially explain that whether induction was allowed in crest and Potomac and were discussed about whether this was not utilized matching Alban. And also how you measure your point, the recurrence was specifically high grade for Potomac and crest. And there was any recurrence on Alban. And if you put all the recurrences, this may potentially have diluted a little bit there and point there. So again, these are just some hypotheses why Alban was negative. But the bottom line is, what is the future? Does this translate in a clinical application? We saw an announcement from the company that so Sassalamab is not approved for this indication, so they will not proceed for now. If we focus on Potomac, the Valumab, this was given for one year of IV administration with BCG versus the alone. As we mentioned, the primary point of disease free survival was met on Potomac. But what does it mean in terms of benefits or risks? These patients, yes, the primary point was met. There was low risk of high grade recurrence in the bladder. However, very few patients had progress on the muscle-based disease or sestectomy, so it would not have enough power to see whether the Valumab made it use the sestectomy rate. And of course, on the other side, you may have the risk of immutilated adverse events. Approximately 20% of patients may have a significant major immutile adverse events. So we have to see what the regulatory agencies will decide. If the company will pursue that, there is a US equivalent trial called Patapsco, which actually ongoing in the US because Potomac and rolled outside US. And the question will be, if that drug gets approved, we don't know if it will. But if it gets approved, the question is, will medical oncologists need to see those patients to discuss pros and cons, benefit risks, rational of sectomy inhibition intravenous lead to Valumab? I think that will be a main question. And it will also create more dialogue about who is managing those patients, urology, medical oncology, who is managing the potential side effects if that were to happen. And also the numbers, the volumes of those patients are many patients, right? But though, thanks so much for summarizing all that. Let me retrace a couple of things that you mentioned, particularly sticking with the two positive trials. That is Potomac with the Valumab and Crest with Cicendlamab. What you mentioned was two years of Cicendlamab, which is subcutaneous therapy. But when compared to Potomac, the Valumab here is for one year. Though the primary endpoint met that is EFS and DFS, has ratio is still similar in both. That is 0.68. We'll have to see how the regulatory approvals play out. But from side effects standpoint, medical oncology ologists will play a big role, especially when we are used to administering immunotherapy and community settings. All right, moving along into muscle invasive bladder cancer space. What we saw data was from EV304 Keynote B15, one of the biggest news GUS code 2026. Our current standard of care is for cis-illigable patients, Gem cytobene, cis-platin, Dervylamab, based off of Niagara study. And then for cis-platin, in-illigable patients, we use EV Pembrolyzumab. What EV304 Keynote B15 is testing for is cis-illigable EV Pembro combination comparison to Gem Cess. But, Rose, can you touch on this study findings and what are we learning from this? Great summary. And everybody was anticipating to see this data by Dr. Galski at Ask OJU. As you mentioned, very correctly, we have a shift in the treatment of metastatic archenoma with EV Pembro being the preferred frontline regimen in metastatic archenoma with EV302 trial. And now more recently, as Motone 25 and Ask OJU N26, we see EV Pembro now taking over as the preferred systemic therapy for localized muscle invasive bladder cancer. And this trial that we see here in this slide, Keynote B15, or EV304, evaluated cis-platin eligible patients, as you mentioned, patients were randomized to new AJU and Gem Cess, the conventional, you know, most common new AJU and regimen in this setting, followed by radical systemic and no plant AJU and therapy. Of course, this has to do with the timing of the trial because AJU and EV305 got FDA approved in the summer of 2021 and very few patients, you know, probably had access to that based on the timing of this trial, a clue. And the experimental arm was EV Pembro, given for four cycles, new AJU, follow by radical surgery, and then AJU van Litha in 10 was, if, of course, tolerated, to give five cycles of the combination, and then eight additional cycles of Pembro alone at the end. So it's a sandwich, perioperative approach, new AJU and AJU. Interestingly, we see the data, it's notable to say that about two-thirds of the patients got the AJU and therapy component, because of patient choice or toxicity or other regions, about one-third of the patients did not get EV Pembro, AJU, and Litha. Having said that, I think the data were astonishing, really remarkable and practiced changing immediately, in my opinion, you see the event-free survival significant hazard ratio 0.53, favoring EV Pembro, perioperatively, compared to new AJU and Zempsis. And also, there was a significant overall survival benefit, hazard ratio 0.65, significant benefit in the first analysis for both EFS and OS, favoring perioperative, EV Pembro compared to new AJU and Zempsis. And this was corroborated by much higher pathology completely response rate, that was 56% in all cameras. And if you look at the subset of patients who got radical systemic to me, there was about 65% or so past CR rate for those who had EV Pembro, new AJU and Zempsis, compared to much lower with Zempsis. Overall, it existed with EV Pembro, it was as expected, there was no new safe signal, we have seen this regimen, how it performs and requires very close attention, of course, like everything we do in terms of education, monitoring of patients to manage potential toxicity. And I think it was reassuring to see that the very similar proportion of patients in both arms under one radical systemic. So if you Pembro in this trial and also in the Kino 905 did not compromise the ability of patients that will go curative intent. constrict to me. And that's important. Of course, as I mentioned, close attention to toxicity, and I think this data actually defy the level one, there's at this point of if you pen, in localized muscle-based blood cancer, we're waiting for the FDA approval in to splat in the eligible patients, but we already have seen FDA approval in to splat in in the eligible patients based on the keynote 905. So overall, these trials go together in my mind, and definitely going to say, I would say significant practice changing is important for our friends and colleagues in community to get familiar with the regimen. I always say this, I admire, you know, people like you, colleagues and friends who will practice the community seeing multiple cancer types, because the data gets on nuance, and fortunately it was only approved in Europhilic as a nomad. So I think getting that familiarity and connecting with colleagues who have used it more, it can help in terms of, again, monitoring and balancing potential toxicity. But, Rose, thanks for touching on that. I want to pick up where you left. When it comes to end-forward to my VDOTEN ADC, side effects that should be on our radar, rash, neuropathy, hyperglycemia. These are the things that we have to worry about. But again, this, indeed, for cis-eligible or ineligible, is now going to be the new standard of care. I have few questions, though. How many EVPembro cycles are good enough? We saw different cycles given in new Agavant and Agavant settings for EV3 or EV3 or EV3 or IV. And also, where will Jempses develop? That Nigro trial regimen set that throws your thoughts. In terms of the dilemma between three and four cycles, for practical reasons, if we think about the trial design, in 0905, there's a split in ineligible patients, there were three new Agavant cycles of EVPembro, and then there was six combination cycles afterwards, and then Pembro alone for a few more cycles. And then if we look at the 15, there were four new Agavant and then followed by five combo and then eight Pembro alone. And this is because of the, you know, try to match up the control arm, right? In suspended ineligible patients, there was no control in new Agavant therapy. So, I would try to get three cycles in the surgery. Suspiting eligible patients, people got at least the intent was to give four cycles of Jempses. That explains that new Agavant cycles three versus four, the number was differently to trials. Now, in clinical practice, I think people, you know, can think about this. I do not think we know that I'd answer. If we look at the pathologic completely response rate, it looks almost the same between three and four cycles, about 56, 57% in all the cameras and about 66% in those wondering when radical surgery. So someone in the first look, and I was thinking about that, I said, maybe three cycles is good enough. Having said that, I will actually go for four cycles tentatively. And there are two reasons for that. Number one, because if we look at the time to event and points in the two trials, they're different. And we try to control micro metastases. So optimizing, you know, new Agavant therapy seems important to me. And also, if we think about radicals, it's tech to me, a big proportion of patients may not make it to us of therapy, the recovery time and potential looks is the so I'm going in my mind back and forth. But for now, I'm landing in the tentative plan of four cycles. If paper is as contaminated, and of course, you can always adjust if needed. The other relevant factor is why patients were not so split in eligible, right? It was it because you have a bigger tumor there, tumor size, hydrogenia process, all these nuances are hard to dissect. I would say it depends, of course, on toxicity, but tentatively, I would probably go for four cycles, you know, just see how patients go with radical surgery. And then my intent will be if we're rated to follow the trial design and give the Agavant therapy phase, if of course there's no major toxicity that gets in the way. Indeed, at the end of the day, I do want to push through now that we have Evie Pembro, we also have James's development at that Niagara Regimen in your clinical practice. Where would that fit in? It's always hard because when the trial is being designed, you know, maybe another trial gets presented and then the sound of care changes. And as you mentioned, you know, James is do Valumab has been the sound of care since Esmo meeting 2024. I think based on the totality of the data, I think that Evie Pembro is the way to go and based on the all this data in the absence of direct comparison with James's do I think the data are robust and I would favor that Regimen in clinical practice. You know, there are open questions, of course. For example, variant histologist subtypes, the keynote B15 and keynote N05 trials and role patients with predominal and urothelial conventional carcinoma. So the question remains open. What do you do in those with predominal or pure non urothelial histologist? And that's an ongoing question through cooperative groups. We may try to design a trial for these patients, but predominal or at least primary urothelial carcinoma, I think Evie Pembro's the way to go. Right, Rahul. I think you were pushing the throws. Where one would utilize this? One should not forget as we were talking Rahul during our discussion as well that one could utilize James's Derva outside of United States, where we are limited with resources. Now with regards to what we also saw a GU ask of 2026 was this debate about CTDNA and also now tying in UTDNA. If any of this can it help us to decide can we do more with the adjuvant or post op management at this point in time? There is no role. Please continue to administer Derva Lama in post op setting. If you are using Niagara trial or Evie Pembro where completion of Pembro for one year time. All right, now moving along into our kidney cancer space, where the adjuvant standard of care has been Pembrolysmab for one year. This was based off of Keynote 564 study. What we saw here at GU ask of 2026 was light spark 0222, which was challenging this standard of care adjuvant Pembrolysmab where the comparison was adjuvant Pembrolysmab versus adjuvant Pembrolysmab plus Belzudufan. And this was rather the largest adjuvant kidney cancer trial that has ever been conducted over 1800 patients were enrolled and then randomized one to one year. For inclusion criteria with Belzudufan, one has to keep anemia and hypoxia in mind as a result patients with hemoglobin less than 10 or underlying pulmonary concerns were excluded. And also, here patients were allowed with M1 NED all the way out to two years. So from finding stand, but what we saw was nice DFS benefit, rather with hazard ratio of 0.72 and curves literally separated very early on and at 30 months what we are seeing the DFS advantage 76% in the combination Belzudufan plus Pembro arm versus 69% with adjuvant Pembrolysmab arm. Though we are still awaiting OS before we completely start adapting this in our clinical practice, we have to wait for regulatory approval, but we cannot forget the side effect profile from anemia and hypoxia standpoint. Rahul, anything to add here? Yeah, Rahul, as you pointed out, this combination is coming with side effects from that Belzudufan. So let's keep that in mind. And also acknowledge that Pembrolysmab is a single agent is doing a good job. At four years, we have update for keynote 564 overall survival being 91 to 92% versus 86%. Then another lightspark study was lightspark 011 using the combination of Lennvatteneb with Belzudufan in refractory settings for RCC. This was after off from IO exposure, and in this particular study, good amount of patients did not get TKI upfront, which ends up being a good chunk of my practice. But I do think that data here is impressive given PFS of 14.8 months with combination versus 10.7 months with Cabo-Zanthaneb, which is the control arm. The hazard ratio here is also 0.70. And another thing that's impressive in this trial, the duration of response almost doubled. Again, side effects, anemia, hypoxia. These are not trivial. So this is important for us to acknowledge. Rahul, the duration of response you're talking about, that's 23 months with Lennvatteneb, and while it was about 12 months with single agent Cabo, so that is impressive. Absolutely. All right, for last few minutes, let's shift gears to prostate cancer. Let's pull Petros back in. But before we jump into capital 28 month study, I do want to mention we also saw data around Poseidon trial. A large meta-analysis, which showed that if PSA is low, adjuvant or salvage radiation might be good enough, and we do not need to add ADT for every single patient. Majority of the benefit from ADT is coming for PSA being over 1.6. Okay, now let's talk to you on the role of PETAN loss in prostate cancer in capital 28 month study looking at CAPEVASER tip. We have this already approved in breast cancer. Petros here. What are we learning from this study? Points, guys. Great discussion overall. And just a couple of comments on what you discussed, looking at the data with the radiation localized disease, we're trying to figure out who is the right and point for those trials. Overall survival, it may take for a long time for those patients with localized prostate cancer. Immatitis, fish survival, maybe relevant, biochemical recurrence, percent-evolving field. Going back to capital 281, we saw the data first time at ESMO, 225 in Berlin, a very interesting data, great discussion there. And I would say that if we look at the study, this is a metastatic hormone sensitive prostate cancer. These are patients who were tested prospectively for PETAN deficiency based on immunosocamistry tests. So IHC, which is readily available, you can argue. you, of course, if it's validated in the local lab, it's easier and potentially faster to obtain, compared to next generation sequencing, although now we all do genomics testing, next generation sequencing, progress the board, and we do both humor, somatic, and germline testing for prostate cancer. And I would say that in that particular trial, the screen pay sense and the, and the in the role patients who had at least 90% of malignant cells with no specific set of plasma extending of P10. So P10 deficiency was defined that way in the study. And these patients were randomized to ADT, others with a version therapy, plus their utter own prednisone, plus minus capivacircate. And this is the question, right? It was a very attractive trial to look whether we can target the biolus of this disease. Capivacity was given at the dose 400 million per day, four days on, three days off, to allow for potential toxicity to resolve in between or at least be manageable. Pramarin point, investigator assessed that the geographic progression of fish survival and the Pramarin point was met. There was numerical difference and this was also reach statistical significance with a significant hazard ratio. If you look at the difference, it's about 7.5 months difference in the median or geographic progression fish survival. However, there was no over-orce survival benefit based on the current follow-up. Of course, follow-up continues based on the number of events. There was no over-orce survival difference. The big question is, is that difference in the radiographic PFS, justifying potential side effects and toxicity that may happen with the capivacircate, for example, diarrhea, lusstool, skin rust, potential parietus, hyperglycemia, fatigue. These are some of the side effects that were described in the study. We saw some quality of life data. PRO based report outcomes, which are always important in these phasedric trials to ask a GU. The jury is still out there. The trial met its primary point. Should be left between providers and patients to decide whether to use their notes. Others say, "Oh, it's only radiographic PFS. No over-orce benefits. There's a consistent cost involved. Some people ask for more follow-up." I think the jury is still out there. I'm following that debate to see what happens. But I think if that drug gets approved, it's important, as you point out before, to look careful in the potential to persist the profile, educate the patients and timely and accurately reporting of potential adverse events. So this can be managed appropriately and optimize the benefit risk ratio. Thanks for covering that, Patreuse. What the trial goes to show is that, first of all, biomarker testing is important because we also have, based on BRCA2 positivity in CSPC space, neuroporephorometastatic disease. Though we need more mature data here. We'll see how regulatory approval plays out. But we do also know that P10 loss is associated with the poor prognosis in prostate cancer. We are, at least from community standpoint, used to using KapiVasertib in breast cancer space. And as you stated, the side effects that we are dealing with are rash, diarrhea, hyperglycemia. Patreuse, we have covered quite a bit here. Thank you so much for walking us through the data from GUASCO 2026. For our listeners, let us go over a quick recap from today's discussion. Today, with Dr. Patreuse Grievous, we highlighted several key studies from ASCO GU26 that are going to impact our clinical practice. In high-risk BCG-9E, non-muscle invasive bladder cancer, we're seeing data from two I/O BCG combination studies, both with hazard ratio of 0.68 with improved disease-free survival and event-free survival. But this is all coming out of cost. We have to keep side effects in financial toxicity in mind. In bladder cancer, we also touched on EV-Pembro based off EV-304 study. This is now going to be the new standard of care for risk-sectable muscle-invasive bladder cancer irrespective of cis-eligible or ineligible criteria. Rolehead, your tea takeaways from kidney cancer? Role, I'll dive into the kidney cancer, but I want to reiterate that EV-304 keynote B15, how impactful the study was. What we are seeing is improvement in PATCR. That is about 56% with EV-Pembro versus 32% with GEMSIS. And this is indeed our new standard of care. Shifting gears into the kidney cancer space. What we saw was Belzudefan with Pembro Lismap as combination in adjuvant setting, which was a positive trial with DFS benefit with hazard ratio of 0.72. Though we need more mature OS data here, but balancing that side effect profile with Belzudefan is going to be the key that is hypoxia and anemia. We also saw another combination trial, which was Belzudefan, Linvatneb in refractory setting, which was also a positive study, which was light spark 011. This will likely get available as well, but tying in the side effect is going to be the key. To close off, we touched on prostate cancer space, where we covered Poseidin study, where we discussed that 80T is not for everyone post radiation in salvage setting. One has to consider PSA in mind. Then we also touched on the P10 loss mutation study, which was Kepetella 281, where the data was initially presented at ASMO 2025, but here we are seeing patient reported outcomes, at least from community standpoint, we have used Kepetella in breast cancer space. Wow, that was quite a bit, Rahul. Thanks so much for everyone who joined us. We will see you soon in our next episode. We are The Oncology Brothers.