Enfortumab Vedotin as Third-Line Treatment Improves Overall Survival for Patients with Advanced Urothelial Carcinoma in the EV-301 Trial

IN THE PHASE 3 EV-301 trial, enfortumab vedotin was shown to prolong overall survival (OS) among patients who had previously received chemotherapy and check-point inhibitors for advanced urothelial carcinoma. En- fortumab vedotin is an antibody-drug conjugate directed against Nectin-4 that was granted accelerated approval by the U.S. Food and Drug Administration (FDA) in 2019 for treatment of metastatic urothelial carcinoma following progression on a platinum-containing chemotherapy and immune checkpoint blockade.

The results of EV-301 were presented during the 2021 ASCO Genitourinary Cancers Symposium, by Dr. Thomas Powles (Barts Cancer Centre, Queen Mary University of London, UK) and published simultaneously in The New England Journal of Medicine. In the trial a total to 608 patients previously treated with platinum-based chemotherapy and then progressed during or after PD-1/L1 inhibitor therapy were randomized to enfortumab vedotin versus investigator choice of chemotherapy (docetaxel, paclitaxel, or vinflunine).

Enfortumab vedotin was found to extend median OS from 9.0 months to 12.9 months without a significant increase in the rate of grade ≥3 treatment-related ad- verse events (51.4% for enfortumab vedotin vs. 49.8% for chemotherapy). Dr. Powles concluded that its “robust” clinical benefit and “tolerable” safety profile indicate that enfortumab vedotin is a new standard of care for advanced urothelial carcinoma Enfortumab vedotin is under investigation in other studies advanced urothelial carcinoma populations, such as EV-201 in platinum-ineligible patients who have progressed on PD-1/L1 inhibitor therapy (data from which have already been published and also presented at this meeting; abstract 394), and in combination with other anticancer agents.

Hiten D. Patel, MD, MPH, completed residency training in urologic surgery at the James Buchanan Brady Urological Institute and is currently a Clinical Instructor and Fellow in Urologic Oncology at Loyola University Medical Center. He has published studies related to epidemiology, comparative effectiveness, evidence-based reviews, and clinical trials in urologic oncology and related fields.


Powles T, Rosenberg JE, Sonpavde G, et al. Primary results of EV-301: A phase III trial of enfortumab vedotin versus chemotherapy in patients with previously treated locally advanced or metastatic urothelial carcinoma. J Clin Oncol. 39, 2021 (6, suppl):99. Abstract 393. doi: 10.1200/JCO.2021.39.6_suppl.393

Powles T, Rosenberg JE, Sonpavde GP, et al. Enfortumab vedotin in previously treated advanced urothelial carcinoma. NEnglJMed. 2021; 384(12):1125-1135. doi: 10.1056/NEJMoa2035807

US Food & Drug Administration (FDA). FDA grants accelerated approval to enfortumab vedotin-ejfv for metastatic urothelial cancer. December 19, 2019. https://www.fda.gov/drugs/ resources-information-approved-drugs/fda-grants-accelerated-approval-enfortumab-ve- dotin-ejfv-metastatic-urothelial-cancer

Rosenberg JE, O’Donnell PH, Arjun V. Balar AV, et al. Pivotal trial of enfortumab vedotin in urothelial carcinoma after platinum and anti-programmed death 1/programmed death ligand 1 therapy. J Clin Oncol. 2019;37:2592-2600. doi: 10.1200/JCO.19.01140

Balar AV, McGregor BA, Rosenberg JE, et al. EV-201 Cohort 2: Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors. J Clin Oncol. 2021;39(6, suppl):99. Abstract 394. doi: 10.1200/ JCO.2021.39.6_suppl.394