Pembrolizumab with or Without Lenvatinib as First-line Therapy for Patients with Advanced Urothelial Carcinoma (LEAP-011): A Phase 3, Randomized, Double-Blind Trial

Abstract

Background: Pembrolizumab plus lenvatinib has shown antitumor activity and acceptable safety in patients with platinum-refractory urothelial carcinoma (UC).

Objective: To evaluate pembrolizumab plus either lenvatinib or placebo as first-line

therapy for advanced UC in the phase 3 LEAP-011 study.

Design, setting, and participants: Patients with advanced UC who were ineligible for

cisplatin-based therapy or any platinum-based chemotherapy were enrolled.

Intervention: Patients were randomly assigned (1:1) to pembrolizumab 200 mg intravenously every 3 wk plus either lenvatinib 20 mg or placebo orally once daily.

Outcome measurements and statistical analysis: Dual primary endpoints were

progression-free survival (PFS) and overall survival (OS). An external data monitoring

committee (DMC) regularly reviewed safety and efficacy data every 3 mo.

Results and limitations: Between June 25, 2019 and July 21, 2021, 487 patients were allocated to receive lenvatinib plus pembrolizumab (n = 245) or placebo plus pembrolizumab (n = 242). The median time from randomization to the data cutoff date