FDA Approves Perioperative Keytruda–Padcev for Cisplatin‑Ineligible Muscle‑Invasive Bladder Cancer

Overview

• Indication covers neoadjuvant treatment followed by adjuvant therapy after cystectomy for adults ineligible for cisplatin, including use with subcutaneous pembrolizumab co-formulated with berahyaluronidase.
• KEYNOTE-905/EV-303 enrolled 344 previously untreated patients and showed median event-free survival not reached with the combination versus 15.7 months with surgery alone (HR 0.40; P < .0001).
• Overall survival was not reached with the regimen versus 41.7 months with surgery alone (HR 0.50; P = .0002), with higher 12- and 24-month survival rates in the combination arm.
• Recommended dosing: neoadjuvant pembrolizumab 200 mg IV every 3 weeks plus enfortumab vedotin 1.25 mg/kg IV on days 1 and 8 for three cycles, then adjuvant enfortumab vedotin for six cycles with pembrolizumab for 14 cycles every 3 weeks or seven cycles every 6 weeks, giving enfortumab vedotin first on coadministration days.
• Safety signals were substantial, with grade 3 or higher adverse events in 71.3%, serious events in 58.1%, treatment-related deaths in 7.8%, dose reductions and discontinuations common, and surgery delays reported in 4.0%.