The FDA has approved the combination of enfortumab vedotin (EV) and pembrolizumab for patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-based chemotherapy, marking a major advance in the neoadjuvant treatment landscape.
Clinical Trial Data:
Approval is primarily supported by results from the EV-103/KEYNOTE-869 Cohort H study, a phase II neoadjuvant cohort evaluating EV + pembrolizumab in cisplatin-ineligible MIBC:
Pathologic Complete Response (pCR): ~36% Pathologic Downstaging (≤pT1): ~55–60% Node-negative residual disease rates were high, suggesting deep tumor responses.
The combination demonstrated consistent activity across clinical subgroups, including older patients and those with ECOG 1 performance status.
The safety profile aligned with known toxicities of EV (cutaneous reactions, neuropathy, hyperglycemia) and pembrolizumab (immune-related events). Most events were manageable with appropriate dose adjustments and supportive care.
Clinical Implications:
This approval introduces the first effective neoadjuvant option for cisplatin-ineligible MIBC, a population historically underserved and often without curative-intent systemic therapy.