51˶

New Combinations Promising in Advanced Urothelial Carcinoma

— Matthew Galsky, MD, leads a discussion with Guru Sonpavde, MD, and John Sfakianos, MD

MedpageToday

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

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 last of four episodes, in which they discuss switch maintenance therapy, as well as some other ongoing studies that may shape the future of advanced urothelial carcinoma treatment.

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 the treatment paradigm for patients with metastatic urothelial cancer has evolved over time, although not quite as much maybe as we expected it might. And we saw the final results from at ASCO GU showing that the improvement in survival barely missed the pre-specified P value threshold for statistical significance. Nonetheless, the hazard ratio was 0.85, and it's not clear if it reached statistical significance, that clinical significance would have been convincing.

And so that approach and similar results from , not as successful a strategy as we've seen in other solid tumors. But of course, switch maintenance therapy has changed the treatment paradigm with initial platinum-based chemotherapy followed by immune checkpoint blockade. And we saw some longer-term data from , and really the results hold up over time.

Guru, what were you excited about at ASCO GU and what are you excited about in terms of ongoing studies that haven't read out yet?

Sonpavde: So at ASCO GU there were no practice changing studies in the urothelial bladder cancer realm. However, we saw some interesting signals in the IMvigor130 trial, although gem [gemcitabine]/platinum plus atezo [atezolizumab, Tecentriq] did not meet the survival bar, there were interesting signals of perhaps the cisplatin/gemcitabine backbone being a better backbone. And as you may know, there was also a similar signal in KEYNOTE-361 for PFS [progression-free survival] with the cis/gem [cisplatin plus gemcitabine] plus pembrolizumab [Keytruda] combination.

So I am cautiously optimistic about the ongoing , which is the trial looking at ipi/nivo [ipilimumab (Yervoy) plus nivolumab (Opdivo)] versus gem/platinum first-line, but also has an interesting substudy looking at cis/gem plus or minus nivo in the cisplatin-based population. So this is the best powered comparison of cis/gem plus or minus a PD-1 inhibitor. And so that would be, I think, an interesting study.

And also in the same study CheckMate901, ipi/nivo could not beat gem/platinum in PD-L1 high patients. That's out there as a , but there is a second comparison, a co-primary endpoint comparing ipi/nivo versus gem/carbo in cisplatin-ineligible patients. That could be interesting. As we know in ASCO GU, atezolizumab in the sub-analysis, a secondary analysis, looked interesting in cisplatin-ineligible patients that were PD-L1 high. Of course we also know that ipi/nivo could not beat gemcitabine/platinum in PD-L1 high.

So at the end of the day that could be an interesting comparison, ipi/nivo versus gem/carbo in cis-ineligible. So I'm cautiously optimistic about that.

Galsky: John, your thoughts about the papillary-only cohort pembrolizumab for non-muscle invasive bladder cancer, we've been waiting that data for a while. And then anything else that you're excited about?

Sfakianos: Yeah, so I do think we were waiting for that data for a while and while we do see maybe a small signal, I'm not really convinced that it's something robust and practice changing, to what Guru was saying. But what I am excited about is all the other non-muscle invasive trials and data that we have seen in GU ASCO. There's a lot of sort of momentum, a lot of excitement around the non-muscle invasive space, which is good for the urologist.

There's two sort of aspects to it that I think are important. One is to better find agents that can compete with BCG [bacillus Calmette-Guérin] in the BCG-naive space. Because as we're seeing now in the BCG shortage, we're having a really difficult time treating our patients timely with the only standard of care we have.

So I'm really excited for Max Kates and the that was presented comparing GEMDOCE [gemcitabine plus docetaxel] to BCG in the naive high-risk patient population. I think that's going to be a very pivotal study when that reads out.

I'm also extremely excited in all the combinations that were sort of ongoing and listed. There's a lot of PD-1 or PD-L1 with other immune checkpoints in the non-muscle invasive space, which is being led by Merck and a couple other companies that I think are going to be exciting to see that data.

So overall, even though we're getting new agents approved for the non-muscle BCG resistant or unresponsive space, I still think that they're not changing our paradigm. They're not going to shift the treatment paradigm, but yet all these other combinations and trials and excitement around the space, the future looks like it's going to be bright. We just have to be patient.

Galsky: Guru, John, thanks very much for your participation and your insights. Anything else you want to add?

Sonpavde: Yeah, Matt, I would like to add of course, we are eagerly awaiting the results, which is of course the trial looking at EV [enfortumab vedotin, Padcev] plus pembrolizumab. Enfortumab vedotin is the antibody drug conjugate already approved in the salvage setting. So that's a phase III trial looking at all comers, first-line cisplatin-eligible or not, cis/gem or carbo/gem as the standard arm, comparing with EV plus pembrolizumab in the experimental arm. So that is of course a huge trial, which could change the paradigm for the first-line setting.

Galsky: Absolutely. Thank you.

Watch episode one: Updated Results on Adjuvant Immunotherapy in Muscle-Invasive Bladder Cancer

Watch episode two: Latest on Neoadjuvant Immunotherapy in Muscle-Invasive Bladder Cancer

Watch episode three: New Approaches in the Bladder-Sparing Paradigm

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    Greg Laub is the Senior Director of Video and currently leads the video and podcast production teams.