Promising OS at 5 Years With Chemo-Free Combo in Urothelial Cancer

Combination therapy with enfortumab vedotin (Padcev) and pembrolizumab (Keytruda) was associated with durable responses and meaningful survival in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer, according to 5-year follow-up results from a phase Ib/II study presented at the recent European Society for Medical Oncology (ESMO) annual congress in Barcelona.

In this exclusive MedPage Today video, Jonathan Rosenberg, MD, of Memorial Sloan Kettering Cancer Center in New York City, discusses the significance of the EV-103 Cohort A findings.

Following is a transcript of his remarks:

In this phase Ib/II trial, 45 patients were initially enrolled who received enfortumab vedotin and pembrolizumab in combination. In fact, this was the first study of the combination, which really established this as a highly active regimen with a response rate that was in the 70% range. And at the time, durable remissions were seen in many patients.

The data that we presented at ESMO this year showed the 5-year outcomes of patients treated on that trial. So this is the longest follow-up of any cohort of patients treated with the combination of enfortumab and pembrolizumab. This data showed that, of course, most patients if not all patients stopped treatment within the first 2 years as dictated by the protocol, but that many patients were able to remain off therapy and stay in remission. And in fact, the duration of responses in responding patients was plateaued at 47% of patients still in remission at 5 years, with 38% of patients were progression free at 5 years, and the overall survival estimate by Kaplan-Meier methods was 41.5% at 5 years.

Now, when we think historically about the outcomes for cisplatin-ineligible metastatic urothelial cancer, the median survival for patients treated with gemcitabine and carboplatin in the EORTC [European Organization for Research and Treatment of Cancer] trial, albeit for many years ago, was about 9 months. In more contemporary trials, the outcomes were 12 to 14 months. So a median overall survival of over 2 years in this cohort, plus most of those patients who were alive at 2 years were alive at 5 years.

And this really is unprecedented. We haven’t seen results like this in advanced urothelial cancer previously. Whether these will be recapitulated in the EV-103 cohort K, which will have longer term follow-up presented in coming years, and the long-term outcomes from EV-302, where the median follow-up was only 17 months, remains to be seen. But it really does appear based on this data that perhaps we are curing a subset of patients with advanced urothelial cancer who were previously thought to be incurable. Whether that number will be 40% or higher or lower is unclear at the moment, but my general sense is we’re going to have more people in the room alive at 5 years than we did previously, and that number is not going to be trivial. Historically, we’d expect that to be 3-10% of patients.

So very provocative and exciting and interesting data, and we’ll look forward to other long-term data as time goes on.