Long-Term Enfortumab Vedotin Results Show OS Benefit in Advanced Urothelial Cancer

Peter O'Donnell, MD

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.

References:

_{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}