The Phase 3 KEYNOTE-B15/EV-304 trial compared a new treatment combination with standard cisplatin-based chemotherapy for patients with muscle-invasive bladder cancer (MIBC). For the first time in 25 years, a non-platinum regimen performed better than the usual cisplatin plus gemcitabine treatment.
Patients received either enfortumab vedotin (EV) plus pembrolizumab before and after surgery, or cisplatin plus gemcitabine before surgery only. The EV/pembrolizumab group had significantly better results. The risk of cancer recurrence or death was reduced by 47%. At 24 months, nearly 80% of patients in the EV/pembrolizumab group had no disease events, compared to about 66% in the chemotherapy group. Overall survival was also higher, and more than half of the patients in the new treatment group had no detectable cancer at surgery.
The new regimen lasted longer and caused more serious side effects, including rash, nerve damage, and lung inflammation, while standard chemotherapy was more associated with kidney problems and hearing loss. Despite the higher rate of side effects, the study establishes EV plus pembrolizumab as a new standard treatment for patients with muscle-invasive bladder cancer.