Novel Therapy in Urothelial Carcinoma: An Evolving Treatment Landscape

Closing out their discussion on urothelial carcinoma, key opinion leaders share clinical pearls and excitement for the evolving treatment landscape.


Shilpa Gupta, MD: Thank you all for this very rich and informative discussion. Before we conclude, I’d like to get some parting thoughts from each one of you. Petros, would you like to share what you’re looking forward to for the future and anything you want to share with the audience?

Petros Grivas, MD, PhD: Shilpa, first of all, I want to express my enthusiasm about this discussion. This was fantastic, and I’m always learning from you, Andrea and Mamta. It’s great to see how the field is rapidly evolving and how we can provide more options for our patients. It’s amazing to see that in the last 6 years we have had all these new agents. We have checkpoint inhibitors, we have 2 antibody-drug conjugates, we have a targeted therapy, all approved literally in the last 6 years, and many more to come. I think in the future we’re looking forward to combinations.

I think we mentioned before the very high promise coming from the enfortumab vedotin [EV]-pembrolizumab combination. This is the frontline setting for cisplatin-ineligible patients based on cohort A and cohort K of the EV-103 single-arm trials. We have to see whether in the next couple of months the FDA may or not give accelerated approval to this combination in the cisplatin-ineligible frontline setting. I think that will be let’s say the most immediate thing we’re looking at, and of course, down the road, the results of the phase 3 EV-302 trial comparing pembrolizumab-EV to platinum-based chemotherapy in the front line. We have to see what those results show, and how many patients get maintenance avelumab in that control group.

Obviously, as discussed before, pembrolizumab-EV is now being investigated in the neoadjuvant-adjuvant setting in the KEYNOTE-905 trial and KEYNOTE-B15. This will be interesting to see. I’m also excited about the potential of sacituzumab plus pembrolizumab. We had some data presented at ASCO GU [American Society of Clinical Oncology Genitourinary Cancers Symposium] 2023, looking at the combination in the second line for platinum-refractory disease, with a more than 40% response rate and a 20% CR [complete response] in the platinum-refractory population, or with early progression on platinum with pembrolizumab-EV in the second line. This merits further investigation, it is not ready for prime time. I hear too, antibody-drug conjugates are also very interesting, and I think we have to look at them. There are phase 2, phase 3 trials looking at anti-HER2 plus antibody-drug conjugates. I think that’s an interesting combination to look at.

I’m also interested and excited to see Andrea’s AMBASSADOR trial as the data mature over time. This trial has DFS [disease-free survival] and OS [overall survival] as coprimary end points, and of course, a huge amount of work is being done across the different stages. I cannot mention anything in this closing remark, but I think the field is rapidly moving forward. I’m seeing in the future both the concept of combinations and the idea of biomarkers, and hopefully with emerging technologies, we can have some composite biomarkers. I know UCL [University College, London] did great work with the PARADIGM study looking at biomarkers. Hopefully we have more and more, and of course definitions of platinum-ineligible patients as well. It’s great to discuss this with all of you.

Shilpa Gupta, MD: Thank you, Petros. Andrea, some parting words of wisdom.

Andrea B. Apolo, MD: I’m also awaiting the AMBASSADOR trial and will be very excited to report about that. It’s such an important trial because the CheckMate 274 study is showing an improvement in DFS, and we want to see what other agents show since the IMvigor010 trial did not show the data. So I’m excited about the AMBASSADOR trial. I’m also excited about the ctDNA [circulating tumor DNA] trials that are being done in the adjuvant setting. I think this is such an important question since we overtreat patients. I was really sad that the IMvigor130 study in the frontline setting, when you combined atezolizumab with platinum-based chemotherapy, did not show an improvement in overall survival. In a subgroup analysis that was exploratory, you did see that there was a bit of an improvement, especially in the cisplatinum arm. Maybe there’s something within the cisplatinum, so I look forward to the CheckMate901 study. They have an arm of NIVO [nivolumab] plus cisplatinum-based chemotherapy in the metastatic setting.

Then there are a lot of efforts of platinum-based chemotherapy plus checkpoint inhibitors in the neoadjuvant setting. You have the NIAGARA study with durvalumab plus GEM-CIS [gemcitabine and cisplatin], and the ENERGIZE study with nivolumab plus gemcitabine and cisplatin. Then you have the KEYNOTE-866 study with pembrolizumab plus gemcitabine and cisplatin. I think that’s going to be really important. Those are randomized phase 3 trials in a neoadjuvant setting, so that’s going to be really important to see if there a particular benefit of adding a checkpoint to the platinum-based chemotherapy in this setting in the muscle-invasive setting.

Shilpa Gupta, MD: There’s so much to talk about. Mamta, would you like to share some last thoughts?

Mamta Parikh, MD, MS: Yes, it’s hard to follow such a wonderful group. I know Petros and Andrea have already talked about a lot of the exciting things that are around the corner for bladder cancer. I also want to take a moment and say that one thing that’s very inspiring in our field is that in bladder cancer, I do feel like we’re listening to the patients about what they want. We have heard that cystectomies are things they would like to avoid, and are really impacting their quality of life. It’s wonderful to see the field listening to that and looking in both the nonmuscle invasive space as well as the muscle invasive space to find those patients for whom we can spare their bladders, and looking at approaches that potentially could get us to bladder preservation for everybody.

I think the RETAIN study was a bit disappointing because we were hoping that they would give us some clear markers on whom we could pick. Even though we saw that there were patients who could have bladder preservation, we didn’t get a clear signal on how to select those patients. I think trials like ADAPT-BLADDER and other things that are looking at circulating tumor DNA are going to be exciting. The SWOG-1806 study is also exciting looking at the chemotherapy RT [radiotherapy] plus IO [immunotherapy] angle as a bladder preservation approach. Again, you all have been doing this longer than I have, and I think it’s commendable that we’re listening to our patient advocates about what they’re looking for from therapy.

Shilpa Gupta, MD: That is a great note to end this on, Mamta, that at the end of the day, patients are centric to all the decisions. Thank you again, and thanks to our viewing audience. We hope you found this OncLive Peer Exchange® discussion to be useful and can take some clinical pearls from our experts. Thank you, Mamta, Andrea, and Petros for your time, and have a great day.

Transcript edited for clarity.

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