Benefit from perioperative enfortumab vedotin–pembrolizumab in cisplatin-eligible MIBC

In the randomized phase 3 KEYNOTE-B15/EV-304 trial (n=808), perioperative enfortumab vedotin plus pembrolizumab outperformed standard neoadjuvant cisplatin-gemcitabine in cisplatin-eligible muscle-invasive bladder cancer. At 2 years, event-free survival was 79.4% versus 66.2% (HR 0.53; 95% CI 0.41-0.70; P<0.001), overall survival was 86.9% versus 81.3% (HR 0.65; 95% CI 0.48-0.89; P=0.006), and pathological complete response occurred in 55.8% versus 32.5% of participants (P<0.001). The trade-off is toxicity: grade 3 or higher adverse events occurred in 75.7% versus 67.2%. The results, published in NEJM (July 2026), challenge the long-standing cisplatin-based standard of care.