Enfortumab Vedotin Improves OS in Patients with Locally Advanced, Metastatic Urothelial Carcinoma

Patients with locally advanced or metastatic urothelial carcinoma receiving enfortumab vedotin had increased overall survival at 12- and 18-month intervals.

Half of patients with locally advanced or metastatic urothelial carcinoma who were treated with enfortumab vedotin (Padcev) monotherapy were alive at 12 months, according to data presented at the European Society of Medical Oncology Virtual Congress 2020.1

Moreover, one-third of patients were also alive at 18 months.

Data from cohort 1 of EV-201 (NCT03219333), a single-arm phase 2 pivotal trial of enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer previously treated with platinum-based chemotherapy and immune checkpoint inhibitors, demonstrated overall survival (OS) rates of 50.4% at 12 months and 34.2% at 18 months, respectively.

The study enrolled 125 patients, with a median age of 69 years and a median of 3 prior systemic treatments. The median follow-up for all patients was 22.3 months (0.5-27.3+), and median OS was 12.4 months (95% CI; 9.46-15.57). Patients received 1.25 mg/kg of enfortumab vedotin intravenously on days 1, 8, and 15 of a 28-day cycle. The median duration of treatment was 4.6 months, with a maximum duration of treatment of 27.3 months (ongoing as of data cutoff).

Enfortumab vedotin is an antibody-drug conjugate that targets Nectin-4, which is highly expressed in urothelial carcinoma.2 The FDA previously granted accelerated approval to enfortumab vedotin based on data that demonstrated an overall response rate of 44%, which was the primary endpoint of EV-201.3 That data indicated that 12% of patients experienced complete response, and the median progression-free survival for patients receiving enfortumab vedotin was 5.8 months (95% CI, 4.9-7.5), with a median duration of response of 7.6 months (range, 0.95-11.30).

The most common treatment-related adverse events (AEs) included alopecia (49.6%), fatigue (49.6%), and decreased appetite (44%). The most common treatment-related AEs that were grade 3 or higher included neutropenia (8.0%), anemia (7.2%), and fatigue (6.4%). Twelve percent of patients discontinued treatment due to AEs, with peripheral sensory neuropathy (6%) being the most common. The investigators did report 1 treatment-related death from interstitial lung disease, confounded by high-dose corticosteroid use and suspected Pneumocystis jiroveci pneumonia.

A confirmatory phase 3 trial, EV-301 (NCT03474107), has completed enrollment. That study will compare OS for patients with locally advanced or metastatic urothelial carcinoma treated with enfortumab vedotin with patients treated with chemotherapy.


1. O’Donnell MD, Galsky JE, Petrylak DP, et al. EV-201: Long-term results of enfortumab vedotin monotherapy for locally advanced or metastatic urothelial caner previously treated with platinum and PD-1/PD-L1 inhibitors. Poster presented at: European Society of Medical Oncology Virtual Congress 2020; September 17-20, 2020. Abstract 746P.

2. Rosenberg J, Sridhar SS, Zhang J, et al. EV-101: A Phase I Study of Single-Agent Enfortumab Vedotin in Patients With Nectin-4-Positive Solid Tumors, Including Metastatic Urothelial Carcinoma. J Clin Oncol. 2020;38(10):1041-1049. doi:10.1200/JCO.19.02044

3. Kahl K. FDA Approves First Agent to Treat Locally Advanced, Metastatic Urothelial Cancer. CancerNetwork. January 15, 2020. Accessed September 17, 2020. https://www.cancernetwork.com/view/fda-approves-first-agent-treat-locally-advanced-metastatic-urothelial-cancer.