The FDA has expanded the indication for perioperative pembrolizumab (Keytruda) or subcutaneous pembrolizumab (Keytruda Qlex), each in combination with enfortumab vedotin (Padcev), to include all adults with muscle-invasive bladder cancer (MIBC) who are candidates for radical cystectomy.

The approval, announced July 10, broadens the regimen’s previous indication, which was limited to patients who were ineligible for cisplatin-based chemotherapy. The pembrolizumab-based combination is now approved as neoadjuvant therapy before surgery followed by adjuvant treatment after cystectomy, regardless of cisplatin eligibility.

The expanded indication was based on results from the phase 3 KEYNOTE-B15/EV-304 trial, which enrolled 808 patients with previously untreated MIBC who were candidates for radical cystectomy with pelvic lymph node dissection and were eligible for cisplatin-based chemotherapy.

Patients were randomly allocated (1:1) to neoadjuvant pembrolizumab plus enfortumab vedotin followed by surgery and adjuvant pembrolizumab plus enfortumab vedotin or to neoadjuvant gemcitabine plus cisplatin followed by surgery.

The trial met its primary endpoint of event-free survival (EFS). Median EFS was not reached with the pembrolizumab-enfortumab vedotin regimen compared with 48.5 months with gemcitabine-cisplatin (hazard ratio [HR], 0.53; P < .0001).

The pembrolizumab-enfortumab vedotin regimen also significantly improved overall survival (OS), with a 35% reduction in the risk for death (HR, 0.65; P = .0029). At the time of data analysis, median OS had not been reached in either treatment group.

The overall safety profile of the pembrolizumab plus enfortumab vedotin regimen was consistent with previous studies of the combination in advanced urothelial cancer, with no new safety signals identified, the FDA said.

Pembrolizumab labeling includes warnings for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity, the agency noted.

Enfortumab vedotin carries warnings for skin reactions, hyperglycemia, pneumonitis/interstitial lung disease, peripheral neuropathy, ocular disorders, infusion-site extravasation, and embryo-fetal toxicity.

Full prescribing information will be posted on Drugs@FDA.

The application received priority review and was approved about 5 weeks ahead of its FDA target action date.