Enfortumab vedotin monotherapy demonstrated significant long-term results in updated findings from the EV-201 trial presented at the 2020 ESMO Virtual Congress.
Enfortumab vedotin (Padcev) monotherapy demonstrated significant long-term results in updated findings from the EV-201 trial (NCT03219333) presented at the 2020 ESMO Virtual Congress.1 At 1 year, half of patients with locally advanced or metastatic urothelial carcinoma treated with enfortumab vedotin were still alive and about one-third were still alive at 18 months.
Data from cohort 1 of EV-201, 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 (range, 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. 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: ESMO Virtual Congress 2020; September 19-21, 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