Dr. Powles highlights data on enfortumab vedotin/pembrolizumab in urothelial carcinoma

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“We have not previously managed to beat first-line chemotherapy in any trial in unselected first-line urothelial cancer, so this is a big step in that direction,” says Thomas B. Powles, MBBS, MRCP, MD.

In this video, Thomas B. Powles, MBBS, MRCP, MD, highlights key findings from the EV-302 trial (NCT04223856), which explored the combination of enfortumab vedotin-ejfv and pembrolizumab in patients with previously untreated locally advanced or metastatic urothelial carcinoma. Powles, who is the lead author of the study and the director of the Barts Cancer Centre at St. Bartholomew’s Hospital in London, presented the findings at the 2023 European Society for Medical Oncology Annual Congress in Madrid, Spain.

Video Transcript:

Approximately 850 patients were randomized 1:1 in this trial. The population was characteristic of urothelial cancer. About 70% had visceral metastasis, about 55% received cisplatin-based therapy, the majority of patients have performance status of 0 or 1. The population was nicely balanced between the 2 arms. The median follow-up with a trial was 17 months. The results showed a dramatic increase in progression-free survival. In fact, there was a hazard ratio of 0.45, a 55% reduction in the risk of progression compared to chemotherapy, which is somewhat unprecedented.

More importantly, we also showed an over 50% reduction in the risk of death, with a hazard ratio of 0.47. We have not previously managed to beat first-line chemotherapy in any trial in unselected first-line urothelial cancer, so this is a big step in that direction. It's important to recognize that there was a high response rate, 68%. CR rate [was] 29%, which is really impressive. The durability of response has not yet been reached. So, this is a very comprehensive efficacy suite of end points, all of which have been hit.

The second component is the adverse event profile. Grade 3 or 4 adverse events occurred with chemotherapy in 70%, and with enfortumab vedotin and pembrolizumab, 56% of patients. Adverse events of special interest with enfortumab vedotin include skin toxicity, peripheral neuropathy, and hyperglycemia, all of which appeared manageable and in line with data we've seen in previous trials. Treatment-related deaths, there were only 4 in both arms. Those were not related to skin, peripheral neuropathy or hyperglycemia in the enfortumab vedotin arm. So, I think it's fair to say that these results are striking and transformative for urothelial cancer patients. I think an over 50% reduction in the risk of death is important, because we've never seen anything like that before in urothelial cancer.

The control arm was platinum-based chemotherapy, 6 cycles; 31% of those patients received maintenance avelumab as well, which became the standard of care during the conduct of the trial. Real-world data suggests that under 50% of patients get maintenance avelumab, so I think that is at least in part a contemporary control arm. And indeed, you can see the control arm performed well in the overall survival component of the trial. It's also important to recognize the benefits were seen irrespective of platinum-based chemotherapy, PDL-1 status, sites, and metastasis. In summary, the trial is a very positive trial, the combination is tolerable and in line with expectations. The drug works across all subgroups of patients. The control arm performed as expected. I think these data will be important for doctors and patients moving forward.

This transcription has been edited for clarity.

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