Thomas Powles, MD, MBBS, MRCP, discusses findings from the phase 3 EV-302 clinical trial of enfortumab vedotin-ejfv with pembrolizumab vs chemotherapy for the treatment of patients with previously untreated locally advanced or metastatic urothelial cancer.
Thomas Powles, MD, MBBS, MRCP, professor of genitourinary oncology at Queen Mary University of London; director, Barts Cancer Center, discusses findings from the phase 3 EV-302 clinical trial (NCT04223856) which evaluated the use of enfortumab vedotin-ejfv (Padcev) combined with pembrolizumab (Keytruda) vs chemotherapy for the treatment of patients with previously untreated locally advanced or metastatic urothelial cancer (mUC).
In the study, the combination of enfortumab vedotin and pembrolizumab led to significant improvements in the dual primary end points of overall survival and progression-free survival.
0:10 | The findings of the trial are exceptionally positive. The overall survival shows a 50% reduction in the risk of death. We've never really seen anything like that in bladder cancer before. Progression-free survival was also a 50% reduction in the risk of progression. We've reproduced those phase 1 and phase 2 data for [enfortumab vedotin and pembrolizumab]. In fact, the data looks, because we've included cisplatin eligible patients here, which I think have slightly better performance data in my opinion, looks at least as good as what we saw in the phase 1 and phase 2 trial.
0:47 | The subset analysis didn't show any particular subgroup where chemotherapy was better, it was really consistently better across the board, irrespective of platinum use, irrespective of upper tract or lower tract disease, irrespective of PD-L1 status, and that was progression-free and for overall survival. The response rate was high in the region of 70%, complete response rate of 30%, and we've not seen that before. Now we'll have to look to see what happens to those patients, but I also have to tell you that those responses were durable, and more durable than with chemotherapy. It's possible that we're putting a group of patients into long-term durable remission. We have not really seen that before either, which is really exciting.
1:36 | The tolerability profile needs to be looked at, of course, and the adverse event profile overall was not that much worse than chemotherapy about. It was about the same as chemotherapy, which I think is reassuring. But remember, [enfortumab vedotin and pembrolizumab] continues until progression, where chemotherapy is only given for 6 cycles. So if you weigh the adverse events for duration of therapy, the frequency of the adverse events on enfortumab vedotin and pembrolizumab is actually lower than what we saw in chemotherapy.