Redefining Urothelial Cancer Care: EV-Pembro, De-Escalation, and Future Strategies

A virtual roundtable, hosted by Dr. Petros Grivas of Fred Hutchinson Cancer Center, contextualized the latest bladder cancer research updates and trials of relevancy to come out of the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium. Dr. Grivas was joined by Drs. Guru Sonpavde, Elizabeth Plimack, Christopher Wallis, Terence Friedlander, and Matthew Galsky.

In the first segment of the roundtable, the panel weighs the impact of long-term survival data from the EV-302 trial, with significant improvements in overall survival and outcomes across various patient subgroups. The conversation also touches on potential strategies to de-escalate treatment, including a pilot trial exploring induction and maintenance therapy to reduce long-term toxicities, and the role of ctDNA in clinical decision-making.

View the next segment on Balancing EV/Pembro and Gem/Cis-Nivo: Selecting the Right 1L Therapy for Node-Only Disease.

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Dr. Grivas: Hello everybody. I am Dr. Petros Grivas, a medical oncologist in Seattle. I am a professor at the University of Washington and the Fred Hutchinson Cancer Center. I am very excited today to be surrounded by amazing superstars and leaders in the field of GU oncology. We are going to have a dialogue about the key data from ASCOGU 2025. Before we dive into this amazing data set, I will ask my colleagues to introduce themselves. We will start with Dr. Plimack first.

Dr. Plimack: Thank you for having me. It is great to be here. I am Betsy Plimack, a GU medical oncologist at Fox Chase Cancer Center in Philadelphia.

Dr. Sonpavde: Hi. I am Guru Sonpavde, the GU oncology and phase one director at AdventHealth in Orlando.

Dr. Friedlander: Super. I am Terry Friedlander, a professor of medicine here at the University of California San Francisco.

Dr. Galsky: Hi, I am Matt Galsky, a GU medical oncologist at Mount Sinai in New York.

Dr. Wallace: Hi everyone. Thanks for having me. I am the lone urologist here in a room of smarter people. I am a GU urologist and urologic oncologist at the University of Toronto.

Dr. Grivas: We appreciate the urologists and we work with them all the time, so thank you for joining. Let us start. Dr. Friedlander, I will start with you. Obviously, you have been involved, along with many colleagues, in the EV-302 trial, which is definitely practice changing. We saw the standing ovation. I remember, Dr. Plimack, we were together sitting next to each other at ESMO 2023. It was wonderful. I want to hear your thoughts about the updated data that Dr. Tom Powles presented at ASCOGU 2025. How would you summarize the data briefly, and what do you think about it?

Dr. Friedlander: At ASCOGU 2025, the updated data for the EV-302 trial was presented. It included about a year’s further update in terms of follow-up. I believe the cutoff was in August of 2024. I would say that the data, for me, was important because it continues to show the benefit. It was not really a surprise, the data that was presented at GUASCO. Rather, it confirmed that EV plus pembrolizumab outperforms cisplatin-gemcitabine in the frontline setting. The hazard ratio for survival was actually a little higher than it was at ESMO. It was around 0.51. However, these are really marginal, very small differences.

Interestingly, the median overall survival in the updated data is now beyond 33 months—33.8 months, to be exact—which is dramatically longer than it was when any of us started our careers, when median overall survival was perhaps around 12 months with frontline platinum-based chemotherapy. Again, the forest plots presented essentially showed that EV plus pembrolizumab outperformed standard chemotherapy in just about every subgroup that was analyzed. These are the major takeaways.

I would like to open this up to my colleagues to see if they had other thoughts about some of the other analyses that were presented. But overall, I think this really confirms EV plus pembrolizumab as the go-to frontline regimen in urothelial cancer for eligible patients. There are patients who have neuropathy or other contraindications, but I believe this is really the standard to beat at this point.

Dr. Grivas: I believe we all agree with you. Dr. Plimack, maybe I will ask your opinion. I know you have been working very hard at Fox Chase with Dr. Ghatalia and others on very important studies for the de-escalation of EV. May I ask your opinion on how you use EV-pembrolizumab today in clinical practice, and how your views on these trial designs for potential de-escalation have evolved?

Dr. Plimack: Thank you for bringing attention to Dr. Ghatalia’s trial. The thing with EV-302, as mentioned, is that EV and pembrolizumab have amazing results. Most patients respond, and very few progress through it. Among those who respond, many have durable responses. That is where these long-term results really matter. We really want to see results from EV-302 ten years from now, showing that patients are still doing well. That would be amazing.

Because EV-302 is so effective and successful, patients are rarely stopped due to disease progression, not as commonly as with chemotherapy. What stops patients more often is toxicity, specifically the longer-term and cumulative toxicities such as neuropathy. Dr. Ghatalia has this idea, and we are conducting a pilot trial at Fox Chase to test this approach before we conduct a larger trial. We are looking at an induction and maintenance approach, similar to what we did with JAVELIN, where we used induction chemotherapy followed by maintenance immunotherapy. This would involve induction with a combination for two cycles, lasting 18 weeks, followed by maintenance immunotherapy for patients with a good response. We are trying to see if we can achieve the maximum benefit from the cytotoxic agents upfront and then maintain with immunotherapy.

We will see how this goes. As the saying goes, with great success comes great responsibility. The better it works, the more we need to focus on using it correctly to achieve the most benefit with the least detriment.

Dr. Grivas: Great points, and thank you for working on these study designs. As you said, it is hard to improve upon pembrolizumab plus EV, and fine-tuning the delivery on a patient-by-patient basis can help us. May I ask you, have you used ctDNA at all to make decisions in this current setting, or do you base those adjustments on toxicity and/or progression?

Dr. Plimack: At Fox Chase, we do not use ctDNA clinically, but we collect it on every trial we conduct. We hope to be able to paint a clearer picture of what ctDNA tells us that is different from imaging.

I will say that in the metastatic setting, the use of ctDNA is very different from the perioperative setting, where we expect some patients to be completely NED (no evidence of disease) and free of cancer. In the metastatic setting, we believe the cancer might always be brewing somewhere. So, would we expect truly negative tests to align with good CT scan results? I do not think we know the answer to that yet. We are starting to gain insights, and there are some publications that suggest ctDNA modulates along with imaging. The correlation appears to be pretty tight. But, I love that question and hope I will have a good answer for it in a couple of years.

Dr. Grivas: I agree with you. I do not use ctDNA in metastatic disease because I do not know what to do with the result, as you mentioned. But I completely agree with you; when we generate this data, it will help us make better decisions.