New Reference: Perioperative Enfortumab Vedotin and Pembrolizumab in Bladder Cancer

In this phase 3 trial, perioperative enfortumab vedotin-pembrolizumab demonstrated significantly better event-free survival and overall survival compared to neoadjuvant cisplatin-gemcitabine in patients with muscle-invasive bladder cancer eligible for cisplatin-based chemotherapy. The enfortumab vedotin-pembrolizumab regimen also resulted in a significantly higher incidence of pathological complete response. However, the enfortumab vedotin-pembrolizumab group experienced a higher incidence of grade 3 or higher adverse events.

Study

Phase 3, open-label, randomized trial [KEYNOTE-B15/EV-304; NCT04700124]

Muscle-invasive bladder cancer eligible for cisplatin-based chemotherapy and radical cystectomy

Neoadjuvant enfortumab vedotin-pembrolizumab (4 cycles) and adjuvant enfortumab vedotin (5 cycles)-pembrolizumab (13 cycles) (n=405) vs neoadjuvant cisplatin-gemcitabine (4 cycles) (n=403)

Efficacy

Pathological CR: 55.8% vs 32.5% (enfortumab vedotin + pembro vs. chemotherapy) (estimated difference: 23.4% [16.7-29.8])

2-yr EFS: 79.4% vs 66.2% (HR 0.53 [0.41-0.70])

mEFS: Not reached vs 48.5 mos

2-yr OS: 86.9% vs 81.3% (HR 0.65 [0.48-0.89])

2-yr DFS: 86.1% vs 72.6% (HR 0.50 [0.36-0.70])

Safety

Grade >=3 AE: neutropenia (7.4% vs 33.1%), thrombocytopenia (0.2% vs 9.1%), diarrhea (2.2% vs 1.0%), anemia (6.5% vs 15.4%), urinary tract infection (9.9% vs 9.6%), peripheral neuropathy (1.5% vs 0.3%)

Serious adverse events: 63.3% vs 48.0%

Death due to adverse event: 4.2% vs 2.8%

Death attributable to trial treatment: 0.5% vs 0.3%