Panelists Discuss Treatment Approach for Patients With Cisplatin-Eligible Bladder Cancer

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 first segment of the roundtable series, the panel discusses the approach to treating patients with cisplatin-eligible bladder cancer.

Watch the next segment in this roundtable series.

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Dr. Koshkin: I thought maybe we’d just start with just generally discussing our approach to patients with metastatic bladder cancer, how we approach initially diagnosed patients in their separation into cisplatin-eligible, cisplatin-ineligible, perhaps platinum-ineligible as well, and whether any data presented at this conference [ASCO 2023] or any recent conferences changes that approach in any way.

Dr. Zibelman: I guess we can start with cisplatin-eligible patients and our thoughts about those. At least for myself and most of our team at Fox Chase, we primarily start with dose-dense or accelerated MVAC [methotrexate, vinblastine, doxorubicin, cisplatin]. We owe a lot of that to Dr. Sternberg. But that is our choice for most patients who are cisplatin-eligible with some exceptions for certain comorbidities. But I find that that is a regimen that we can get patients through fairly well with really great response rates, and some patients with long-term responses.

Dr. Sternberg: That’s good to hear. I love that regimen, and it’s my favorite regimen, particularly in younger patients who can tolerate it. I really believe that when they tried to prove that gemcitabine/platinum was better and they said it was equal, that the study a long time ago didn’t prove that. But having said that, working in New York City and working with a much [more] elderly population, I would say that I’m often using gemcitabine and platinum if the patients have a lot of comorbidities or are elderly. And not only using that, but using it in split doses, giving half of it on day 1 and half of it on day 8, always for patients who are cisplatin-eligible with creatinine clearance of more than 60.

Dr. Petrylak: Cora makes an excellent point. That trial that [Dr.] von der Maase did a number of years ago was not designed as an equivalence trial, and the reason why the gemcitabine/cisplatin was accepted as a standard of care was on toxicity. At that time, we weren’t using growth factors, and use of growth factors has really made the use of MVAC more applicable to patients who may be a little bit less fit, that they could tolerate the neutropenia or at least we could overcome the neutropenia in that situation. I think both choices are acceptable but MVAC, of course, because we have a common mentor who invented MVAC, Alan Yagoda, MD, it’s dear to our hearts.

Dr. Koshkin: What do you see as the role of switch maintenance therapy in this patient population?

Dr. Petrylak: Clearly, switch maintenance therapy is useful in those patients who are responding, and when we define response, that includes those patients with stable disease. Clearly, there’s an improvement in survival in patients treated with avelumab maintenance. Unfortunately, although the label is MVAC, is included, in that original trial, MVAC was not the primary chemotherapy treatment that was used. It was either gemcitabine/cisplatin or gemcitabine/carboplatin. But still, I think that it’s appropriate to give that. No matter what your primary chemotherapy regimen is, you need to get to that response or stabilization to see the benefit.

Dr. Sternberg: I tried very hard when the JAVELIN 100 Bladder trial was being designed to put MVAC in there but, for some reason, people only wanted gemcitabine/cisplatin or gemcitabine/carboplatin. But then all the guidelines have picked up with combination chemotherapy with dose-dense MVAC, not even with MVAC, that we should be doing the switch maintenance.

In fact, in patients who have had even stable disease, but CR or PR or stable disease, we have 24 months of median follow-up in patients giving them avelumab maintenance. I think that that’s much better than what you see is if you wait until patients progress and then give them second-line pembrolizumab or atezolizumab or whatever we were giving in the past. I think it makes a lot of sense.

They’ve also done a lot of analysis showing that whether or not they got platinum, whether they got carboplatin/platinum, whether they had CR or PR or even stable disease, all of these patients have benefited by the switch maintenance, which means not waiting until they’ve progressed and just immediately putting them on avelumab, which is a little bit hard to give because it’s every 2 weeks. But I can tell you that after chemotherapy, most patients are not complaining about even every 2 weeks immunotherapy.

Dr. Koshkin: Yeah. It’s certainly a lot more tolerable.

Dr. Zibelman: I think you make a good point, and I think really the benefit of that approach is capturing the people who were destined to progress quickly and getting them on treatment right away and finding some of those that benefit. It’s at the expense to probably a small group of patients that can have long-term responses to platinum treatment and who could go on and not necessarily need immediate immunotherapy. I discuss it with all my patients. Most do choose to go on to maintenance, but I have had some who just, after chemotherapy, feel like they need a break and would rather do that. We’ve done that.

Dr. Petrylak: It’s actually surprising from the Flatiron data that only about 20% of patients are getting switch maintenance therapy. It’s extremely disappointing that that’s happening. We need to get the message out that this is an effective treatment for patients with metastatic urothelial cancer.

Dr. Koshkin: Do you think that is a consequence of this data initially coming out during COVID? I think it was like ASCO 2020 or so.

Dr. Petrylak: I think that’s partly it. I think also patients do get tired of going on treatment, and perhaps that the commitment of continuous immune therapy is something that may be concerning to them. I think really, the issue is, is it the patients who are deciding not to go on the treatment or is it the physician who’s not offering that in that situation? I think that clearly needs to be defined.

Dr. Sternberg: I haven’t had that problem. None of my patients have said no. But mainly because they’re coming to a major center. It might be different than if they’re in the community or there may be differences. The only patients that I’m not 100% sure about are those patients who had CR, although these are all retrospective looking at the CR, PR, and stable disease. The curves look like they benefited, but I’m not 100% sure how accurate that is because it’s hard to tease that out.

Dr. Koshkin: On that note also, is there a certain number of cycles you aim for before? Do you push to 6 cycles, or can you stop earlier?

Dr. Sternberg: The idea with this study was to give between 4 and 6 cycles, and then we looked back at the data and patients, whether they’ve had 4, 5, or 6 cycles, all of them would benefit from switch maintenance. I try to give 6 cycles when it’s possible, but maybe not always possible, especially in those carboplatin patients who are not as fit.

Dr. Koshkin: Maybe if you have a patient after 4 cycles who has already a pretty good response, not tolerating it well, you can transition them to maintenance. Otherwise, maybe push to 6.

Dr. Zibelman: I tend to do 3 cycles, re-scan patients, see if they’re responding, and then define the number of additional cycles based on really tolerability at that point. If they’re having a great response at 3, I try to get at least a fourth in. If they’re doing great, we’ll push it more. If they’re having a tough time at that point, we’ll often talk about switching after 4 cycles and moving to maintenance at that point.

Dr. Koshkin: I also want to bring up there is some data for pembrolizumab used as switch maintenance as well. The label is not for pembrolizumab, it’s for avelumab. But I wonder what your guys thoughts are on that.

Dr. Sternberg: Matt Galsky, MD, presented the Hoosier Oncology Group. It was a very small study. It was a phase 2 randomized study with 50 patients in each arm. It wasn’t looking at overall survival, and everyone on the arm not getting pembrolizumab was crossed over to pembrolizumab. I think in some countries like Greece, for example, where they don’t have avelumab, they’re using pembrolizumab as the switch maintenance, and probably in other countries as well, as far as I know. But we don’t really have the data. We only have that one small study.

Dr. Petrylak: That brings up a fundamental question. Is there a difference between checkpoint inhibitors? We’ve had 2 checkpoint inhibitors lose their accelerated approval status based upon lack of confirmation and subsequent trials. Are these drugs really interchangeable? We really don’t know. But the one thing about pembrolizumab, which is different than avelumab, is the schedule. You certainly can give pembrolizumab by a Q6-week schedule, which makes it a lot more attractive for patients than giving avelumab every other week.

Dr. Zibelman: No, I agree. I’ll cop to the fact that I have done that for patients and used pembrolizumab in more of a maintenance strategy really for patient convenience. I’ll usually start it every 3 weeks, but then switch to every 6 weeks, and it’s definitely a lot easier for patients.

Dr. Petrylak: We’re all in big cities where patients are fairly close to our practices, where maybe in the Midwest or somewhere out west where the physicians are fairly far away, that may be a difficult issue.

Dr. Koshkin: In my experience, the pushback I’ve gotten from patients for avelumab is the every 2-week schedule. That can be tough sometimes. Pembrolizumab does offer an option there.