The FDA has expanded the approval of pembrolizumab (Keytruda) or the subcutaneous formulation Keytruda Qlex, in combination with enfortumab vedotin (Padcev), for adults with muscle-invasive bladder cancer (MIBC). The regimen can now be used before surgery (neoadjuvant therapy) and after bladder removal surgery (adjuvant therapy) for all patients who are eligible for surgery, regardless of whether they can receive cisplatin chemotherapy.
The approval is based on the phase 3 KEYNOTE-B15/EV-304 trial, which enrolled 808 previously untreated patients with muscle-invasive bladder cancer. Patients received either pembrolizumab plus enfortumab vedotin or standard chemotherapy with gemcitabine and cisplatin.
The combination significantly improved outcomes. Median event-free survival had not yet been reached with the new regimen, compared with 48.5 months for chemotherapy, reducing the risk of disease progression, recurrence, or death by 47%. It also lowered the risk of death by 35% and achieved a pathologic complete response rate of 55.8%, compared with 32.5% for chemotherapy.
Side effects occurred at similar overall rates in both groups, although serious and severe side effects were more common with the combination therapy. The most common safety concerns include immune-related reactions from pembrolizumab and skin reactions, high blood sugar, lung inflammation, and nerve damage from enfortumab vedotin.