ESMO 2025 | Challenges and treatment selection in cisplatin-ineligible urothelial cancer
Terence Friedlander, MD, University of California, San Francisco, CA, gives an overview of the challenges faced by patients with cisplatin-ineligible patients with advanced urothelial cancer. Understanding resistance mechanisms to enfortumab vedotin and immunotherapy is important, as well as selecting patients who will respond to treatment, particularly those with subtype histology or variant histology who tend to have poorer responses. This interview took place at the European Society for Medical Oncology (ESMO) 2025 Congress in Berlin, Germany.
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Transcript
So there are a number of challenges that these patients face. They have a poor prognosis to begin with because they generally have poor renal function, significant neuropathy, and other challenges. So I think finding effective therapy for them is really important. What we’ve seen with EV and Pembro is that we’re able to get about 20 to 30% of patients with long-term durable responses...
So there are a number of challenges that these patients face. They have a poor prognosis to begin with because they generally have poor renal function, significant neuropathy, and other challenges. So I think finding effective therapy for them is really important. What we’ve seen with EV and Pembro is that we’re able to get about 20 to 30% of patients with long-term durable responses. Question is, what happens to those other 70% of patients? And I think there are a lot of unresolved questions. For example, how does resistance to enfortumab vedotin happen? Is it resistance to the payload? Is it resistance because the target is downregulated, Nectin-4? Or are there other mechanisms? Or maybe both of those are happening at the same time. And then the same is true for immunotherapy, which is a broader problem across all of oncology. So I think finding better therapies is paramount. Also selecting patients, trying to understand who is going to respond from the outset so we can avoid giving ineffective therapy to patients who don’t need it. Patients with what we call subtype histology or variant histology also face an uphill battle because they tend to not respond as well to these treatments. There’s some data at this meeting that suggests that they may respond to EVP, but we need larger data sets to really confirm that.
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