Durvalumab, Tremelimumab, and Enfortumab Vedotin in Muscle-Invasive Bladder Cancer.

Perioperative durvalumab plus neoadjuvant enfortumab vedotin improved 24-month event-free survival to 63.5% versus 45.1% with radical cystectomy alone in cisplatin-ineligible/declined muscle-invasive bladder cancer.

• Why it matters: It addresses whether perioperative durvalumab, with or without tremelimumab, combined with neoadjuvant enfortumab vedotin can improve outcomes beyond surgery alone for patients who cannot receive cisplatin-based chemotherapy.
• What they did: In this phase 3 open-label trial, patients were randomized 1:1:1 to neoadjuvant durvalumab-enfortumab vedotin for three cycles plus radical cystectomy, then adjuvant durvalumab, versus radical cystectomy alone; event-free survival was the dual primary endpoint.
• The result: The durvalumab-enfortumab vedotin group had a hazard ratio of 0.51 (95% CI, 0.38 to 0.67; P<0.001) for event or death, and 71.1% had grade 3 or higher adverse events.