Goals of Maintenance Therapy in Metastatic Urothelial Carcinoma

Transcript:

Shilpa Gupta, MD: Petros Grivas, MD, PhD, you’ve done some work with the maintenance therapy with sunitinib in the past when we did not have immunotherapy, and, of course, you called out the JAVELIN Bladder 100 trial (NCT02603432). Can you describe for our audience what kind of different maintenance approaches exist in solid tumors, especially bladder cancer?

Petros Grivas, MD, PhD: For sure, yeah, it has been a historical effort. Thomas Powles, MD, from Queen Mary University in London, myself, and I think others in Europe, have tried different options. About 10 years ago, at the ASCO-GU [American Society of Clinical Oncology Genitourinary] 2012 Annual Meeting, we presented data with maintenance sunitinib, switch maintenance approach after chemotherapy, looking at PFS [progression-free survival] in a randomized phase 2 study. Maha H. Hussain, MBChB, from the Northwestern University Feinberg School of Medicine in Chicago, Illinois, was my mentor during fellowship, and I was leading the trial, and it was a negative trial. The switch maintenance sunitinib did not improve PFS, and there were efforts with lapatinib by Thomas Powles, MBBS, MRCP, MD with vinflunine. I think Joaquim Bellmunt, MD, PhD, and others have worked as well in this setting.

Overall, we have not been able to produce meaningful improvements in PFS based on those trials early on and the question of maintenance therapies still remained. Just for definition, continuation maintenance is when you are in treatment, for example, with gem-cis-pembro [gemcitabine/cisplatin plus pembrolizumab] and you continue with the pembro [pembrolizumab]. That’s continuation maintenance. That approach with concurrent chemo-IO [chemotherapy immuno-oncology] has not worked, as Andrea B. Apolo, MD mentioned before. The switch maintenance is you give chemotherapy first and then you switch to a different modality, a different mechanism of action, avelumab in the JAVELIN Bladder 100 trial. This seems to work very well with overall survival and PFS benefit.

I would say despite the failed attempts of the past with TKIs [tyrosine kinase inhibitors] and some chemotherapy, I think the switch maintenance immunotherapy seems to have changed the paradigm and did change the paradigm, but I think it’s also relevant to the mechanisms of action, immune checkpoint inhibitions. I think it’s ideal for that maintenance approach for different theoretical mechanisms. Of course, it has to go through the test of the phase 3 trial and where JAVELIN Bladder 100 was positive. We’re also very excited about your trial, Shilpa, MAIN-CAV [NCT05092958], with carbo [carboplatin]-avelumab vs avelumab alone. That will also ask a very important question.

Shilpa Gupta, MD: Thank you, Petros, for supporting it through the ECOG [Eastern Cooperative Oncology Group]. I want to ask Mamta about the logistics. When do you first introduce maintenance therapy to your patients? Do you feel you need to do it when you’re starting chemotherapy, or do you wait for their scans? How receptive are patients usually to the concept?

Mamta Parikh, MD, MS: In terms of the discussion with the patient, I usually start the conversation close to the time that I’m about to get scans. I like to prepare patients maybe a cycle or 2 in as long as they’re tolerating therapy well, that if they are responding to therapy, that maintenance would be an option for them. I think the biggest question that I get often for maintenance therapy that MAIN-CAV will get some data on is, how long do I have to be on it? As you all know, in the JAVELIN 100 study, patients were treated indefinitely with avelumab. There was no cap to when patients were off therapy, even if they were maintaining their response. Whereas in MAIN-CAV, I believe the cutoff is 2 years for patients who are responding to therapy, so I think we’ll get some interesting data from that about the duration of immune therapy. That’s the big thing. I think just the logistics of having to come in for infusions regularly.

On the other hand, all of us lived in the era prior to maintenance therapy, and we have these patients who had excellent responses to platinum-based chemotherapy, and there’s a lot of anxiety when you tell a patient, “Well, you’ve responded well, so now we’re going to watch you.” Some patients get a lot of comfort out of the fact that they’re on a maintenance therapy that’s going to keep their disease under control.

Shilpa Gupta, MD: Thank you, Mamta. Andrea, in your practice, the phase 3 level 1 evidence is, of course, from the JAVELIN Bladder 100 trial, but we also have a phase 2 trial of pembrolizumab vs [the] placebo through the Hoosier Cancer Network that was led by Matthew Galsky, MD. Are there any situations where you offer maintenance pembrolizumab?

Andrea B. Apolo, MD: Yeah, I think the issue with maintenance avelumab is the every-2-week visits and infusions, and that can be very difficult. So in situations where patients cannot come that frequently, we can give maintenance pembrolizumab at a 6-week schedule, which the phase 2 study was a randomized study of pembrolizumab vs observation in the maintenance setting. That one was every 3 weeks, but now we do have a 6-week schedule for pembrolizumab that is safe and effective in other tumors that we can extrapolate and use for the maintenance settings. In those settings I think maintenance pembrolizumab is reasonable.

Shilpa Gupta, MD: Thank you. Mamta, we saw even more updates on the JAVELIN Bladder 100 trial at ASCO-GU 2023 what was your takeaway from that? Were you reassured by that or were you surprised?

Mamta Parikh, MD, MS: I don’t think there was a big surprise from this data. This was a longer-term follow-up from the JAVELIN 100 study, and it really continued to confirm that there is an overall survival benefit for patients receiving avelumab. The patients who received cisplatin did very well, so that was just further confirmation that cisplatin is a very powerful drug, so no surprises there. But it’s definitely assuring that maintenance is a robust approach for patients who are receiving platinum-based chemotherapy.

Transcript edited for clarity.