Long-term outcomes in EV-301: 24-month findings from the phase 3 trial of enfortumab vedotin versus chemotherapy in patients with previously treated advanced urothelial carcinoma.
Jonathan E. Rosenberg, Thomas Powles, Guru Sonpavde, Yohann Loriot, Ignacio Durán, Jae‐Lyun Lee, Nobuaki Matsubara, Christof Vulsteke, Daniel Castellano, Ronac Mamtani, Chunzhang Wu, Maria Matsangou, Mary S. Campbell, Daniel P. Petrylak
Abstract
4516 Background: Enfortumab vedotin (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. Clinical trial information: NCT03474107.