Enfortumab vedotin in previously treated advanced urothelial carcinoma

BACKGROUND: Patients with advanced urothelial carcinoma have poor overall survival after platinum-containing chemotherapy and programmed cell death protein-1/programmed death-ligand 1 (PD-1/L1) inhibitor treatment. METHODS: EV-301 is a global, open-label, phase 3 trial of enfortumab vedotin in patients with locally advanced or metastatic urothelial carcinoma who had previously received a platinum-containing chemotherapy and experienced disease progression during or following treatment with a PD-1/L1 inhibitor. Patients were randomized 1:1 to receive enfortumab vedotin 1.25 mg/kg on Days 1, 8, and 15 of a 28-day cycle, or investigator-chosen standard docetaxel, paclitaxel, or vinflunine. The primary endpoint was overall survival. RESULTS: Overall, 608 patients were randomized to enfortumab vedotin (n=301) or chemotherapy (n=307). As of July 15, 2020, a total of 301 deaths (enfortumab vedotin, n=134; chemotherapy, n=167) had occurred. At the prespecified interim analysis, the median follow-up was 11.1 months. Overall survival was prolonged with enfortumab vedotin compared with chemotherapy (HR=0.70 [95% CI: 0.56–0.89]; P=0.00142; median overall survival: 12.88 vs 8.97 months, respectively). Progression-free survival was also longer in the enfortumab vedotin group compared with the chemotherapy group (HR=0.62 [95% CI: 0.51–0.75]; P<0.00001; median progression-free survival: 5.55 vs 3.71 months, respectively). Rates of treatment-related adverse events were comparable between enfortumab vedotin (93.9%) and chemotherapy (91.8%) groups; events of grade ≥3 severity were also comparable (51.4% and 49.8%, respectively). CONCLUSIONS: Enfortumab vedotin significantly prolonged survival over standard chemotherapy in patients with locally advanced or metastatic urothelial carcinoma who previously received platinum-based treatment and a PD-1/L1 inhibitor. (ClinicalTrials.gov number, NCT03474107