Enfortumab Trial For Bladder Cancer Has Practice-Changing Implications

Thomas Powles, MD, MBBS, MRCP, professor of genitourinary oncology, director of the Bart Cancer Centre, and lead for Solid Tumour Research at Cancer Research UK, discusses the implications of the positive outcome of the phase 3 EV-301 trial (NCT03474107) of enfortumab vedotin (Padcev) in patients with urothelial cancers.

The EV-301 trial investigated the monoclonal antibody enfortumab vedotin as a targeted therapy in patients who had previously received platinum-based chemotherapy and progressed during or after receiving a PD-1 or PD-L1 inhibitor. Investigators found an overall survival (OS) benefit to enfortumab of 12.88 months versus 8.97 months (HR, 0.70; 95% CI, 0.56-0.89; P = .001).

According to Powles, this trial is the third to show a signal of OS in patients with urothelial cancer, following the KEYNOTE-045 trial (NCT02256436) of second-line pembrolizumab (Keytruda) and the JAVELIN Bladder 100 trial (NCT02603432) of maintenance avelumab (Bavencio). Powles anticipates that enfortumab will be a standard-of-care regimen with potential as a second-line treatment, though it is currently approved following chemotherapy and a PD-1/PD-L1 inhibitor.

TRANSCRIPTION:

0:08 | This research is practice changing. We've not had many OS signals in urothelial cancer over the last 40 years. We know chemotherapy is active, but there weren't really randomized trials to show that. We had a survival signal for second-line pembrolizumab. We had a survival signal for maintenance avelumab, but we haven't really had any other survival signals in bladder cancer. So, this is the third time we've achieved that with a new class of drugs in a very heavily-treated population.

And so, I think this is going to make a massive difference. I think it's going to be a standard of care. I think, for me, the standard of care currently is platinum-based chemotherapy and maintenance avelumab and giving [enfortumab] on progression, which would be a second-line agent essentially, so we’ll be reaching toward this very quickly.