How Do Prior Therapies in the Perioperative Space Inform Subsequent Treatment Selection?

A roundtable discussion, moderated by Vadim Koshkin, MD, of the University of California, San Francisco, focused on treatment selection for different patient populations with advanced bladder cancer, including a discussion of new data presented at ASCO 2023. Dr. Koshkin was joined by a panel that included Matthew Zibelman, MD; Cora Sternberg, MD; and Daniel Petrylak, MD.

In the next segment of the roundtable series, the panel discussed how treatments used in the metastatic space are moving into the perioperative setting, thus impacting subsequent treatment selections.

Watch the next segment in this roundtable series.

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Dr. Koshkin: One other point I wanted to touch on is, and actually something we briefly discussed, which is that increasingly, some of the drugs we’re using in the metastatic space are moving earlier in the perioperative space, adjuvant nivolumab being a key one. How does that affect your subsequent treatment decisions? Would you, for instance, consider an enfortumab/pembrolizumab combination for someone who previously progressed on adjuvant nivolumab? Would you not use a checkpoint inhibitor again? How do you guys…

Dr. Sternberg: Nobody knows what to do. I’m definitely giving an adjuvant nivolumab. If they progress right away, I’d probably give them enfortumab vedotin (EV) alone. I don’t give them EV post-pembrolizumab. That’s what I’ve been doing in those patients. Because if they progress on their first scan after they just finished 17 cycles or whatever how many cycles, you know? Actually, it’s 1 year.

Dr. Zibelman: We’ve created a new population and we have no data, so I think it’s hard to know. I think the timing of when they progress is definitely really important. Did they get neoadjuvant chemotherapy or not? Have they had that? How long of a benefit do they have, or if none at all? I think that all factors in. We don’t know in urothelial cancer the benefit of continuing immunotherapy. If we extrapolate from CONTACT-03 in kidney cancer that we’re going to see, there doesn’t appear to be a benefit in kidney cancer patients for continuing the immune checkpoint inhibitor. If I had to bet, I would suspect it will be the same in urothelial carcinoma, and I think that will be true. But I mean, we don’t know.

Dr. Sternberg: The only data we have is 1 year of nivolumab adjuvant. I stop at 1 year, and then I rescan.

Dr. Zibelman: Yeah, right. But I mean to your point about do you do EV alone or would you continue with EV/pembrolizumab, for example. I think it’s hard to justify continuing EV/pembrolizumab in those patients, but we don’t know.

Dr. Koshkin: Well, re-treating…

Dr. Zibelman: Or re-treating.

Dr. Petrylak: The other way of looking at that is what’s the downside of getting the pembrolizumab? Is there much of a downside of more toxicity giving it later on again? Certainly, if you believe that there is synergy, true synergy, between the 2, then it’s justified doing so. But if you are concerned about toxicity and cost, then single agent is the appropriate thing.

Dr. Zibelman: I’ll go on the ledge and say, I’m concerned about toxicity and cost, and I’m not a true believer in synergy at this point. I think we’ve seen a lot of additivity and not a lot of synergy, but I don’t think we really know for sure.

Dr. Koshkin: Even with EV/pembrolizumab?

Dr. Zibelman: Even with EV/pembrolizumab. I remain unconvinced that there’s true synergy. But I think it’s hard to prove that, and I don’t think we really know.

Dr. Sternberg: I’ve seen absolutely wonderful responses with EV/pembrolizumab in patients who are cisplatin-ineligible, giving that first line. Once I’ve given adjuvant nivolumab for a year, I just can’t justify giving immunotherapy again right afterwards.

Dr. Petrylak: Also remember too, that the definition of second-line therapy was arbitrary. It was a bunch of docs getting in the back room and basically saying 1 year is our cutoff point. There’s no biological reason behind that.

Dr. Koshkin: That’s a great point. Yeah, if maybe those patients are re-treated with even checkpoint inhibitor monotherapy, they would still do well.

Dr. Sternberg: Maybe with time, but not right away.

Dr. Petrylak: Cora alluded to this before. Even looking back when we were thinking about giving MVAC [methotrexate, vinblastine, doxorubicin, cisplatin] again, the red herring at that time was a trial that was done that gave dose-intense MVAC to patients who had failed prior MVAC. When you looked at that data, there were responses in it, but the responses seen were more than 18 months out after the original treatment with MVAC. When do you lose that resistance mechanism? We really don’t know. Of course, it may be completely different immune therapy.

Dr. Koshkin: Well, again, I think this highlights what an exciting space this is right now with many available options that weren’t available even a few years ago and how, as you mentioned, we’re actually creating new patient populations but we’re not quite sure what to do because of the many options that we have.