Maintenance Therapy for mUC: Current Trials and Future Directions


Genitourinary oncology experts discuss clinical trials of maintenance therapy for urothelial carcinoma and their clinical impacts.

Daniel Petrylak, MD: There is 1 other maintenance study that has looked at pembrolizumab. Matthew Galsky, MD, ran that trial. He looked at a PFS [progression-free survival] difference, not a survival difference. The trial was not blinded, it was not designed to look for a survival benefit as the first end point. It’s suggestive that there may be an improvement with switch maintenance. But of course, there’s no survival benefit with that trial. This is the only checkpoint that has level 1 evidence supporting its use in the situation. Pembrolizumab does not have that level 1 evidence in this clinical state. The other thing I think is going to be important to note is that now that if you’ve progressed on switch maintenance, that brings agents such as enfortumab up earlier, or erdafitinib, or sacituzumab for that matter. These will now be used earlier and we need to make sure that physicians are aware that these treatments are available. Finally, we are seeing trials that are looking at neoadjuvant treatment and using checkpoints as certainly these are being moved up earlier. There’s a lot to think about.

The 1 thing I don’t want investigators, clinicians, and pharma getting discouraged with is that the trial designs are now more complex. It’s almost like when you’re thinking about going to the moon, you don’t aim where the moon is now, you aim where it’s going to be in 4 days. That’s where I think we have to start going with the field thinking ahead and how we’re going to sequence these agents.

Donald Barry Boyd, MD, MS: One of the things I brought up with you earlier in the week is we have to think bigger about how the immune response works. There’s growing data that there are a lot of contributors. So we think of using chemotherapy as a way of inducing enhanced immune response. But how else can we do that, or what else can suppress it? And in both melanoma and now again, in lung cancer, there are 2 studies showing the time of day you give the checkpoint inhibitor determines the response. Now, these are retrospective analysis, but they’re really substantial differences. It’s related to what we know is the diurnal immune response that is typical in the trafficking of lymphocytes that occur with a diurnal rhythm. And there may be real evidence that giving it earlier in the day is better than giving it later in the day. The same thing applies when you give vaccines, they’re more effective early in the day than later. Almost had me go back and get a repeat COVID-19 vaccine when I heard that.

Daniel Petrylak, MD: It’s going to be interesting to see how this all plays out in terms of physiology. Clearly we need some good control trials to tell us what’s going on in that situation. But again, I think that these are great points. We need to think about these in terms of our studies. We need to design rational trials with good biological markers to help us determine what’s the best way to go about these treatments, and when’s the best time to administer them.

Barry, as always it’s a pleasure speaking to you about different studies as well as different preclinical aspects of immune therapy. I’d like to close this particular session of “Avelumab first-line maintenance in locally advanced or metastatic urothelial carcinoma.” Thank you foryour attention.

Donald Barry Boyd, MD, MS: And thank you, Dan, for having me. It was quite enjoyable.

Transcript edited for clarity.

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