51成人动漫

In this exclusive roundtable video from 51成人动漫, three expert leaders in the field of bladder cancer discuss the latest emerging data presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium (GuCS).

Moderator , of the Icahn School of Medicine at Mount Sinai in New York City, is joined by , of AdventHealth Cancer Institute in Orlando, and , also of the Icahn School of Medicine at Mount Sinai, in this first of four episodes, in which they discuss the latest immune checkpoint blockade data in the adjuvant setting.

Following is a transcript of their remarks:

Galsky: Hi, my name's Matt Galsky from the Icahn School of Medicine. Welcome to this roundtable on bladder cancer news from ASCO GU 2023. I'm thrilled to have with me Dr. Guru Sonpavde from Advent Health Orlando, and Dr. John Sfakianos from the Icahn School of Medicine at Mount Sinai.

So we're going to start by talking about adjuvant immune checkpoint blockade in bladder cancer, and at ASCO GU this year we saw the updated results from the CheckMate-274 study. And when that study was initially presented, there was a minimum follow-up of 5.9 months, and at that time there was an improvement in disease-free survival with adjuvant nivolumab [Opdivo] versus placebo in both the intent-to-treat population and in patients with tumors with high PD-L1 expression, ultimately leading to FDA approval of adjuvant nivolumab in that space.

So now we have median follow-up of 3 years, and the effect size for disease-free survival in both the intent-to-treat population and in patients with tumor PD-L1 expression greater than or equal to 1% has held up quite well. The hazard ratios are almost identical to slightly improved compared to the initial presentation. And we also see improvements in secondary and exploratory endpoints with adjuvant nivo versus placebo, including distant metastases-free survival and progression-free survival too.

So Guru, tell us a little bit about other adjuvant studies that have been done in this space that are ongoing, and what do you make of the state in total?

Sonpavde: Right, so the other key trial that has been presented is the , which was not placebo controlled. And this was in the same setting of high-risk muscle-invasive urothelial carcinoma. And that study, as we know, was overall negative unfortunately, but there was an interesting signal, strong signal, of improvement in outcomes in patients with minimal residual disease [MRD] based on a tumor-informed ctDNA platform. So that is being tested prospectively as we speak.

And there's also a second study that's ongoing, which is looking at adjuvant pembrolizumab [Keytruda] in exactly the same population, high-risk non-muscle-invasive urothelial carcinoma with or without neoadjuvant chemotherapy. And in this, the difference is that the endpoints, the co-primary endpoints, of event-free survival and overall survival, so it's not looking at a PD-L1 and intention to treat. So those are the two key trials that either have been done or pending.

There is, of course, another trial being planned through the Intergroup, which you are involved in, Matt, which is looking at adjuvant nivolumab versus nivolumab plus relatlimab, the LAG-3 inhibitor, in patients who are ctDNA positive. And the ctDNA-negative patients are going to be randomized, I believe, to nivolumab versus surveillance, with the surveillance group getting nivolumab upon ctDNA becoming detectable. So maybe you want to tell us a little bit more about that.

Galsky: That's right, and that study is working its way through internal reviews and hopefully we'll get up and running this year.

So we don't have overall survival data yet from CheckMate-274. It's an event-driven analysis and it hasn't matured yet. So in clinical practice, Guru, are you using adjuvant nivolumab? Do you use PD-L1 testing to make that decision?

Sonpavde: Yes, I am using adjuvant nivolumab, although survival has not been presented in the study, and in Europe as we know, nivolumab was approved only in the PD-L1-high population as opposed to the U.S. where it's approved in the overall population regardless of PD-L1 status.

But the median DFS improvement, I believe, is fairly impressive in the intention-to-treat population -- 11 months versus around 22 months, or a doubling of median DFS. I have been impressed by that. I think that a DFS improvement in the adjuvant checkpoint inhibitor setting is highly likely to translate to improved survival. We have shown that in the perioperative chemo setting, in the perioperative immune checkpoint inhibitor setting it has not been shown. If anything, the duration of benefit with immune checkpoint inhibition is more impressive, not less impressive, more impressive. And so I think that the chances are high, but of course we need to wait for the data for survival.

Galsky: John, tell us a little bit about MRD testing with ctDNA. What's that all about? Are you using it in the clinic?

Sfakianos: Yeah, so I think it's an experimental analysis that has come a long way over the last 10 years or so, because this is something that has been of great interest for many people and many investigators, to be able to use it as a biomarker to be able to actually identify the patients that would probably benefit the most from a variety of different treatments, including adjuvant. So, the ctDNA now could be tumor-agnostic or tumor-specific in terms of having panels that are more, you know, not specific to the patient's tumors but more pan-tumor specific.

So there's a few different platforms out there. I do think that the tumor-specific platforms are the ones that are sort of the more useful for quote, unquote personalized medicine, if we're allowed to use those terms anymore. And it's something that I think is really important in helping guide us in terms of both treatment escalation and treatment de-escalation for patients, for having the ability to determine if there's any molecular residual disease around. So I do use ctDNA quite often with our invasive bladder cancer patients, and I do think it's useful both in the initial diagnosis for confined disease, as well as for post-surgery and obviously for the metastatic setting in terms of treatment responses.

Galsky: So, lots going on in this space on new drugs, new mechanisms of action, and new tools potentially to refine the use of these treatments.

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