Long-term outcomes in EV-301: 24-month findings from the phase 3 trial of enfortumabvedotin versus chemotherapy in patients with previously treated advanced urothelial carcinoma.
Background: Enfortumabvedotin (EV), an antibody-drug conjugate directed against Nectin-4, demonstrated longer overall survival (OS) and progression-free survival (PFS) in the confirmatory phase 3, randomized, open-label EV-301 trial at the prespecified interim analysis. The longer-term clinical profile of EV is unknown. Data from 12 additional months of follow-up in EV-301 are presented.
Methods: In EV-301 (NCT03474107), patients with locally advanced or metastatic urothelial carcinoma (la/mUC) who had received a prior platinum-containing chemotherapy and had disease progression during or after PD-1/L1 inhibitor treatment were randomized 1:1 to receive either EV 1.25 mg/kg on Days 1, 8, and 15 of each 28-day cycle or investigator-chosen standard chemotherapy with docetaxel, paclitaxel, or vinflunine. The primary endpoint was OS; secondary endpoints included investigator-assessed PFS per RECIST v1.1, as well as safety and tolerability. Efficacy and safety findings from July 30, 2021, approximately 1 year after the interim analysis (July 15, 2020), are reported.
Results: Overall, 608 patients with la/mUC were randomly assigned to EV (n = 301) or chemotherapy (n = 307). As of July 30, 2021, 444 deaths had occurred (EV, n = 207; chemotherapy, n = 237). After a 23.75-month follow-up, median OS was significantly prolonged by 3.97 months with EV compared with chemotherapy (median OS: 12.91 vs 8.94 months, respectively; HR = 0.704 [95% CI: 0.581-0.852], 1-sided P= 0.00015). Additionally, the OS benefit of EV was retained in the majority of prespecified subgroups. PFS also was improved with EV (median 5.55 months) vs chemotherapy (median 3.71 months) (HR = 0.632 [95% CI: 0.525-0.762]; 1-sided P< 0.00001). Rates of treatment-related adverse events (TRAEs; 93.9% vs 91.8%), including serious TRAEs (22.6% vs 23.4%), were comparable between the EV and chemotherapy groups. Rates of grade ≥3 TRAEs were ̃50% in both groups.
Conclusions: EV continues to show significant and consistent survival advantage over standard chemotherapy in patients with treatment-experienced la/mUC. No new safety signals were identified. With robust clinical benefit and a tolerable safety profile, EV maintains its place as a standard of care for this aggressive disease.
Research Sponsor:Astellas Pharma, Inc.