Highlights From the 2026 ASCO GU Cancers Symposium

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KEYNOTE-B15 (EV304) Trial Results

Andrea Apolo summarizes EV304 design and reports improved event-free and overall survival for EV plus pembrolizumab.

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Dr. Monty Pal and Dr. Andrea Apolo discuss practice-changing studies and other novel approaches in bladder, kidney, and prostate cancers that were presented at the 2026 ASCO Genitourinary Cancers Symposium.

TRANSCRIPT

Dr. Monty Pal: Hello and welcome to the ASCO Daily News Podcast. I'm your host, Dr. Monty Pal. I'm a medical oncologist, professor and vice chair of academic affairs at the City of Hope Comprehensive Cancer Center in Los Angeles.

And today is super exciting, we're highlighting key abstracts that were presented at the 2026 ASCO GU Cancers Symposium, and I'm just delighted to be joined by the chair of this year's meeting, who is also a dear friend, Dr. Andrea Apolo. Dr. Apolo serves within the Center for Cancer Research at the NCI as head of the Bladder Cancer Section, and she is also acting deputy chief of the Genitourinary Malignancies Branch.

Welcome, Andrea, it is so great to have you on the podcast.

Dr. Andrea Apolo: Oh, thank you so much for having me. What a great ASCO that we had, it is really exciting, lots of really great data. So I look forward to chatting about it.

Dr. Monty Pal: Excellent. And you know, our full disclosures are available in the transcript of this episode in case our listeners want to have a peek.

The theme of this year's GU meeting was "Patient-Centered Care: From Discovery to Delivery." I love that theme. And really, this is one of the most competitive meetings out there, more than 850 abstracts being presented on high-impact science. Andrea, I just wanted to get right into it and dive into what I think we both felt were some of the most exciting abstracts of the meeting.

And the first of those is one that I know is near and dear to your heart, being a bladder cancer expert yourself, and that is the KEYNOTE-B15 study presented by Matt Galsky. Can you give us a flavor for what that study entailed and some of the key results?

Dr. Andrea Apolo: Yeah, I think this was kind of the missing study that we have been waiting for since we saw the EV-302 data in metastatic disease in the frontline setting. We wanted to know how well this combination would work in muscle-invasive bladder cancer patients. And we saw half of that puzzle, you can say half of the piece of the puzzle, when we saw the data at ESMO, the EV-303 data in patients that were cisplatin-ineligible. And then now we are getting the full story with patients that are platinum-eligible, cisplatin-eligible, with the EV-304 data. So that study randomized patients to receive chemotherapy, so different than the EV-303 where the patients were randomized just to receive the radical cystectomy. These patients were randomized to receive neoadjuvant EV plus pembro and then adjuvant EV plus pembro versus neoadjuvant gemcitabine and cisplatin with no adjuvant component to the control arm. So I think this is a really, really important study.

Dr. Monty Pal: And share with us some of the results because this in my mind is definitely practice-changing. This is one of those studies that I think you walked into the office on Monday and you are like, "Okay, this is what I am doing now," right?

Dr. Andrea Apolo: Yeah. So the study was positive. The primary endpoint was event-free survival, and it met the primary endpoint. The secondary endpoint of overall survival was also met. So really, really great results. Consistent with what we saw with EV-303, the median event-free survival was not reached for the EV plus pembro arm, and it was 48 months for the patients receiving gem-cis. And then looking at the 24-month estimated event-free survival, it was 79% for the EV plus pembro and 66% for the chemo, the gem-cis arm. And that was a hazard ratio of 0.5. So that is really exciting. That is the event-free survival. And then the overall survival, the medians were not reached for either arm, but when you look at the 24-month estimated overall survival, it was 87% for the EV plus pembro versus 81% for the gem-cis, and that was a hazard ratio of 0.65. So very positive study.

And then another question that we had was the pathologic CR rate. Very consistent with what we saw with the EV-303, the pathologic response rate was about 56% for the patients that received EV plus pembro and about 32%, 33% for the patients that received gem-cis. So very consistent with the findings that we have been kind of seeing in phase 2 studies, and this is a pT0N0, so that is important.

Dr. Monty Pal: So Andrea, you know, I think that the big question in folks' minds is at this point, we see the data from NIAGARA, cis-gem-durva, we have now seen this data. Put it into context for us. Is there a patient in this day and age who maybe shouldn't get IO altogether, who should maybe get the NIAGARA regimen as opposed to EV-pembro in this context? What are your thoughts there?

Dr. Andrea Apolo: Now, that is a great question. I would say with this data, it is very enticing to give EV pembro to our patients in the perioperative setting, and for that to be the new standard of care for all patients, regardless of cisplatin eligibility. So similar to what we saw with EV-302 really changing the standard of care in the frontline setting, I think these two studies, the EV-303 and the EV-304, change the standard of care for patients with muscle-invasive bladder cancer in the perioperative setting, and this should be the new standard of care if the patients don't have a restriction to receiving an immunotherapy.

Dr. Monty Pal: I totally agree with that assessment. It is great to hear it from the expert's mouth as well. Thanks a lot for that, Andrea.

The next abstract I wanted to tackle is one that is, I would say, near and dear to my heart because I know these folks really well. It is led by the SWOG group, and this is SWOG S1602. The number there for the audience gives you a sense of how long the study has been running for. The 16 prefix means it is something that we kicked off back in 2016. So this study is really 10 years in the making, right? So Rob Svatek presented this data. It is interesting, right, because it addresses this issue of the BCG (Bacille Calmette-Guérin) shortage, right, where we have needed to sort of rely potentially on other alternative sources or regimens and so forth. Tell us about this trial, Andrea.

Dr. Andrea Apolo: This is one of my favorite studies. We talked about putting it in the main oral abstracts, but we put it in one of the educational sessions that talked about non-muscle-invasive bladder cancer because we thought that would be the best audience for it. But it doesn't take away from how important this abstract is, and the tremendous effort that went into the study. Almost a thousand patients enrolled. I think 984 were eligible to enroll in this study. So it is a very high enrolling, randomized, cooperative group study in high-grade non-muscle-invasive bladder cancer. And really the study was designed to address two questions. One is the BCG shortage and can we use a different strain, Tokyo versus TICE? And whether there is a priming effect if you gave intradermal BCG to patients with non-muscle-invasive bladder cancer, can that enhance the effect if you gave it a little bit earlier?

I think the study is really important, and it met its primary endpoint, which was it is not inferior to TICE. The findings were really terrific in terms of the outcomes. Numerically. When you look at the endpoint, it looked like the Tokyo strain was as good, if not maybe a little bit better, but not statistically significant than the TICE. And then they broke it down by carcinoma in situ, they broke it down by papillary tumors, and the Tokyo strain was non-inferior in both of those instances. But interestingly, the intradermal BCG did not change outcomes. There was really no priming effect, which was really backed up by pre-clinical data that there would be, but there wasn't a priming effect when the intradermal BCG was given in the Tokyo strain. So that was a really, really interesting finding. But a great study, really important outcomes in the field for non-muscle-invasive bladder cancer.

Dr. Monty Pal: Totally. And it just seems like we can't get away from BCG, right? You know, as hard as we try, I mean, I appreciate the studies that sort of build on it that are emerging right now, but it seems like BCG at least for the foreseeable future is kind of here to stay, right?

Dr. Andrea Apolo: It works. It is one of the most effective treatments we have for non-muscle-invasive bladder cancer. So, you know, I think it is here to stay and, you know, we need to find alternatives in terms of strains so we don't deal with this shortage that we have been dealing with for so many years now.

Dr. Monty Pal: Yeah, indeed. Moving on to some of the other highlighted studies from the meeting, you had mentioned the EV-303 data, so we probably don't need to rehash that study design in much detail. But there was also a rapid oral abstract presented by Dr. Ullén that I think is of interest here, right, that really hones in on pathologic outcomes and DFS from that trial. Do you mind just outlining that for our listenership?

Dr. Andrea Apolo: This is the KEYNOTE-905, also known as the EV-303 study. This is a follow-up to the EV-303 data looking at the pathologic response rates, looking at the downstaging effect, looking at the surgical margins after treatment with the neoadjuvant EV plus pembro in the 303. Now, remember in the 303, patients got three cycles of neoadjuvant EV plus pembro and then six cycles in the adjuvant setting. A little bit different than the 304, where they got four cycles, which is really kind of the standard in the neoadjuvant setting, and then five cycles in the adjuvant setting. So still a total of nine cycles. But in the 303, the treatment arm had no systemic therapy, so it was just radical cystectomy. And they looked at the negative margins that you get with the EV plus pembro treatment, which was 92.6% versus 79% with patients receiving just the surgery alone. And then the pathologic CR rate, there was more follow-up on that, it was 57% for the patients receiving EV plus pembro, and as we would expect, about 9% for the patients that just went on to surgery alone because you can achieve a pathologic response rate with TURBT alone. Then they looked at the pathologic downstaging, so anything less than a pT2, and that was 66% in the patients that received the EV plus pembro.

So very interesting findings, and it is also really just nice to have now the EV-304 data, like I was saying, there were two pieces of it, the cisplatin-eligible and the cisplatin-ineligible, and just to have those contemporary controls are really important. How did the cisplatin-ineligible do versus the cisplatin-eligible patient in terms of the event-free survival and in terms of the overall survival? So I feel like now we have all of this data that we can kind of put together in the perioperative setting and we can really inform our patients a little bit more about their outcomes depending on whether they are cisplatin-eligible or not, which you know cisplatin-ineligible patients often just, they are sicker, they may have obstruction, their tumors may be larger, they just tend to be a more delicate population than the cisplatin-eligible patients. So not surprisingly, you know, we see that in the EV-303 the disease-free survival for the patients is pretty poor. So the disease-free survival that was reported for this follow-up of the specific abstract was 23.6 months for the patients that just got surgery, and it was not reached for the patients that had the EV plus pembro, and that was a hazard ratio of 0.37.

Dr. Monty Pal: Excellent, excellent distillation. So Andrea, in the interest of time, I mean, we could probably talk about bladder cancer forever, but I am going to move us on to the subject of kidney cancer. We have two late-breaking abstracts, LITESPARK-011, which looked at lenvatinib and belzutifan versus cabozantinib in the advanced setting, and then we have an adjuvant study, LITESPARK-022, that looked at pembrolizumab with or without belzutifan in the adjuvant setting. Both studies positive. One for progression-free survival, the other for disease-free survival. Both I think making a big dent in how we treat kidney cancer. Can you tell us a little bit about that?

Dr. Andrea Apolo: Yeah, we have been waiting for these trials for a long time. So one of the things that we have been talking about at GU ASCO is to have plenary sessions. And if we would have had a plenary session, these two abstracts would have been part of it because they are important data, really big studies where we are trying to improve the outcomes of our patients with kidney cancer. So the first one, the LITESPARK-011, like you said, this is for advanced renal cell carcinoma, clear cell renal cell carcinoma, where we really don't have a standard of care after IO therapy, right? So we give IO-IO, we give VEGF-IO, but we don't really have a good standard of care. We usually give monotherapy TKIs. So the combination of belzutifan and lenvatinib versus what a standard of care is, cabozantinib, is really an important question to ask. And you know, this is a pretty large study, about 750 patients were randomized. And belzutifan plus lenvatinib demonstrated an improvement in progression-free survival and overall survival versus cabozantinib, but not overall survival, at least not yet, is what the authors are saying.

So for the progression-free survival, the hazard ratio was 0.7 and it was 14.8 months for the combination, belzutifan plus lenvatinib arm versus cabozantinib, which was 10.7 months. So I think that is significant. And for the overall survival, it did favor the combination again with a hazard ratio of 0.85. The median was 35 months versus 28 months for the monotherapy cabozantinib, but it did not reach statistical significance. And the authors said that this will be further tested at a final analysis, these were the interim results.

And for the overall survival, the overall survival was 53% for the combination versus 40%. This is significant. And the CR rates were lowish for both of them, it was like 5% for the combo and 1% for cabo monotherapy. So I think that the findings are important because we don't have a standard of care. And although there is no survival benefit, there was a trend. So I think this could be considered in patients that are fit, a treatment option for these patients in the later line settings.

Dr. Monty Pal: Great points. I mean lots of great discussion around toxicity as well as efficacy. I mean certainly this is a regimen that may not be suitable for every patient in my portfolio, but certainly one to consider.

Now Andrea, let's shift focus to LITESPARK-022, the adjuvant trial that I mentioned previously. So this is again looking at pembrolizumab with or without belzutifan, met the primary endpoint of disease-free survival. What are your impressions there of the data?

Dr. Andrea Apolo: Yeah, the data looks great. And this was a really large study, 1,800 patients were randomized, and the study met the primary endpoint of disease-free survival, benefiting the combination of pembro plus belzutifan. And that is really terrific. The medians were not reached for either arm. And in terms of the overall survival results, also the medians were not reached, but the hazard ratio was 0.78 and did not reach a statistical significance. So there was again a statistically significant improvement in disease-free survival for the combination of pembrolizumab plus belzutifan, but not an overall survival benefit.

So I guess, Monty, you know, we can kind of talk about what that means. There was a lot of discussion about belzutifan and some of the side effects, specifically anemia and managing anemia in this setting and requirements for transfusions. Generally, the authors said it was well tolerated, but we know that combination studies do have more toxicity. So it may be a select group of patients again, similar to the advanced setting, where we opt for a combination, possibly until we see more follow-up data in terms of the overall survival.

Dr. Monty Pal: I have to agree with you. You know, in my group, we have been talking about a lot of pembrolizumab-based studies that are running right now, some through the NCI, some, you know, our own sort of homegrown investigator-sponsored trials, and you know, I think for the foreseeable future we are comfortable just maintaining pembrolizumab. Things might change if, for instance, we ultimately see a survival advantage emerge, but I just have my own personal doubts around that, that will be interesting.

Okay, so now we are going to move to the last disease category that we are going to cover, which is prostate cancer. So there, we have the long-awaited results from the PEACE-3 study. These are the final OS results from this trial looking at enzalutamide with or without radium-223 in metastatic castration-resistant prostate cancer. So Andrea, would love to get your perspectives on this.

Dr. Andrea Apolo: Yeah, so this study had been presented before and we had seen positive results for the combination of enzalutamide and radium with some interim overall survival results also showing a benefit. But like you said, these are the final results with a median follow-up of 58 months. So it was really nice to see the final results. And with the combination of enzalutamide and six cycles of radium, it did show an improvement in overall survival with a hazard ratio of 0.76. The median overall survival increased from 32.6 months to 38.2 months with the combination. So that is really great. There was some crossing over of the overall survival curves around 18 months was still seen. And again, there was also an improvement in the rPFS with a hazard ratio of 0.71, and the median rPFS improved from 16.4 to 19 months with the combination. So, you know, we have been awaiting the final results, but we kind of knew a lot about the benefits of the combination. And it is something that is kind of slowly trickling into the community in terms of adapting it and using it. There is more buzz now about it and I think these overall survival results will hopefully shift the community into incorporating the combination in these patients.

Dr. Monty Pal: Brilliant. So well said. I mean, Andrea, congratulations on a terrific meeting. You have really done it again. Incredible, incredible output from this year's ASCO GU. I just want to thank you for joining us on the program today.

Dr. Andrea Apolo: Oh, thank you so much for having me, Monty. It was really a joy to work with the ASCO team and with all the investigators and the Education Committee and the Scientific Committee. Everyone was really outstanding. So to me it was an honor to be part of this meeting, and I am so happy that it was so successful and really presented some amazing data that I think will be practice-changing to our patients.

Dr. Monty Pal: Oh, thanks a ton. And also a huge thanks to our listeners. If you enjoyed the content of today's podcast, please don't forget to like and subscribe to our channel wherever you listen to podcasts. Thanks so much.

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