Zachary Klaassen: Hi, my name is Zach Klaassen, urologic oncologist at the Georgia Cancer Center. We're on UroToday at ASCO 2025 in Chicago, Illinois. Delighted to be joined on today by Dr. Ali Khaki, who is a medical oncologist at Stanford University. Ali, thanks for joining us.

Ali Khaki: Hey, Zach. Thanks for the invitation.

Zachary Klaassen: We're going to talk about a really important topic. We've seen a huge boom in immune checkpoint inhibitor therapy in urothelial carcinoma, particularly as we move earlier lines. So you guys looked at a survey of, what do we do after people have had immune checkpoint inhibitor therapy, what are they doing in that first line metastatic setting. So maybe just set the scene about this huge boom that we've seen in this disease space.

Ali Khaki: Yeah. Thanks. This survey was born now about 18 months ago after ASCO GU in 2024.

Zachary Klaassen: Awesome.

Ali Khaki: That was on the heels of the EV pembrolizumab approval for first line metastatic disease, and also in the setting where we've had KEYNOTE study that showed pembrolizumab in the non-muscle invasive bladder cancer setting and adjuvant nivolumab. And then more recently, we've seen the SANDWICH trial for durvalumab, the NIAGARA trial, as well as now CREST that we saw here. And so there's more and more data of using immune checkpoint inhibitors for non-muscle invasive or muscle invasive bladder cancer.

And so naturally, the question is, can we still use immune checkpoint inhibitors for metastatic disease, and, especially in the setting of what we know about kidney cancer, where we've had two negative studies? The CONTACT-03 study, as well as the TiNivo-2 study, that have shown a combination of IO TKI after prior IO exposure had limited efficacy and increased toxicity.

Zachary Klaassen: Yeah. Very relevant. Like you said, we're now in the non-muscle invasive bladder cancer space, BCG naive, sassy BCG unresponsive pembrolizumab. The survey is super relevant. Just tell us a little bit about the survey, some of the key questions you guys asked.

Ali Khaki: Yeah. First, what we did is after that ASCO GU in 2024, we compiled a panel of about 11 medical oncologists from around the country and built the survey questions. We asked questions both about sequencing after EV pembrolizumab in the metastatic disease setting, which we presented at ASCO GU earlier this year. Priyanka Chablani, my co-author and colleague, was the first author of that poster presentation. And now, this is looking at in that non-metastatic disease setting. And so we asked questions around, would you use first line EV pembrolizumab or gem/cis nivolumab, which has also been shown to have efficacy in the first line metastatic setting in patients who had prior exposure to immunotherapy.

There are a couple of things that we thought were different from the RCC setting, where these patients had non-metastatic disease, which is different than most of the patients in TiNivo-2 and CONTACT-03.

Zachary Klaassen: Sure.

Ali Khaki: Many of them could have had, many years ago, for example, the non-muscle invasive bladder cancer. So that interval matters. So we asked questions about the interval and what people even use these medications. Different disease, different medications, different intervals makes this a very relevant question.

Zachary Klaassen: Yeah. Great survey. What were the key results that you guys found?

Ali Khaki: Yeah. We sent the survey out to about 200, just over 200 medical oncologists, had about 70 of them respond. About 88 % of them were in academic practice. And just over 2/3 of them had been in practice for more than five years and saw 25 or more patients.

Zachary Klaassen: Wow.

Ali Khaki: So it was a pretty experienced group of experts. And I'm going to go to the glasses here for some of the specific results.

Zachary Klaassen: Absolutely.

Ali Khaki: Tony Kornheiser style. And so, when we ask people about the interval after, would they give EV pembrolizumab after any interval or after 3, 6, 9, or 12 months.

Zachary Klaassen: Yeah.

Ali Khaki: There was a third of providers who would feel comfortable giving EV pembrolizumab after just about any interval. They thought that there might be enough synergy in that combination that regardless of if you progressed on an adjuvant nivolumab or progressed on a non-muscle invasive disease, EV pembrolizumab would still be rational to give. There were another almost 45 % who were comfortable giving it at some interval. There were less than 5 % who would just never give EV pembrolizumab after prior progression on some prior earlier-stage immune checkpoint inhibitor.

Zachary Klaassen: That's great. So, basically, I think because the EV pembrolizumab data is so good, people are willing to give it a shot, which I think is the right answer.

Ali Khaki: Yeah, I think so too. There's hope that there could be synergy in that. There's, at least, biologic rationale for possible synergy. And so I think it's worth giving that trial. Now, contrast that to the gem/cis nivolumab data, where there's a lot less enthusiasm for using that, so going back to the glasses here.

Zachary Klaassen: Yeah.

Ali Khaki: Only about 10 % of providers would give it irrespective of the interval. And there were about 20 % to 25 % who would never give it.

Zachary Klaassen: I see.

Ali Khaki: And some others who would depending on the interval in the middle. And you can see the abstract for the full numbers.

Zachary Klaassen: A little less excitement in that trial.

Ali Khaki: Exactly.

Zachary Klaassen: So I think surveys are awesome because it gives us a lot of insight to what people are doing, but also some hypothesis on maybe how this impacts clinical practice or future trial design. What are your thoughts on those?

Ali Khaki: Yeah. So when we set out to do this survey, our main goal was to see if we could develop some consensus that could help guide practice in this area where we have a vacuum of real data. And, unfortunately, I don't think we have clear consensus, maybe a little bit more leaning towards consensus for having a stronger consideration for EV pembrolizumab.

Zachary Klaassen: Sure.

Ali Khaki: But I think that what this still does that's helpful is that it helps give some guidance to practitioners about EV pembrolizumab probably is something more likely to be beneficial, at least, hypothesized by the experts without data, compared to gem/cis nivolumab. And it helps us as we're thinking about a new generation of clinical trials. How would you pick your control arms?

Zachary Klaassen: Sure.

Ali Khaki: And so picking a platinum immunotherapy control arm after progression in the adjuvant setting or in the non-muscle invasive bladder cancer setting would probably be inappropriate, at least, based off the sentiment from this, of course, without data. But very clear that there is an impression that EV pembrolizumab is the real first line metastatic disease regimen.

Zachary Klaassen: Yeah. Great summary. Anything we haven't hit on, anything you want to tell our listeners in concluding statements?

Ali Khaki: I think that it's been such a fun journey, a wonderful journey to work on this. I'm really grateful to our whole working group of experts. I'm so grateful to my co-authors, especially Priyanka Chablani and Karine Tawagi, who really were with us every step along the way in this. And then Peter McDonnell and Petros Grivas were our senior mentors and then others on the full committee. So really, really appreciative of all the support.

And then keep an eye out. We're working on the manuscript that will summarize both the data that Dr. Chablani had presented back in February and also this data. So, hopefully, that will be out sometime this year.

Zachary Klaassen: Fantastic. Great summary. Always good to thank your co-authors. Thanks for joining us, Ali.

Ali Khaki: Thanks, Zach.