Among patients with locally advanced or metastatic urothelial carcinoma, treatment with pembrolizumab in combination with lenvatinib did not improve progression-free survival (PFS) and overall survival (OS) when compared with pembrolizumab alone, according to findings presented at the 2022 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium.

The randomized, double-blind, phase 3 LEAP-011 study ( Identifier: NCT03898180) evaluated the efficacy and safety of pembrolizumab plus lenvatinib vs placebo in 441 adults with histologically confirmed, locally advanced or metastatic urothelial carcinoma who were cisplatin-ineligible with tumors expressing programmed cell death-ligand (PD-L1) (combined positive score ≥10) or who were ineligible to receive platinum-based chemotherapy regardless of PD-L1 status. The coprimary endpoints of the study were PFS and OS.

Patients were randomly assigned 1:1 to receive lenvatinib 20mg orally once daily (n=218) or placebo (n=223), in addition to pembrolizumab 200mg intravenously every 3 weeks for up to 35 cycles. Median duration of treatment was 3.8 months for the lenvatinib arm and 3.4 months for the placebo arm.

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Median PFS was reported to be 4.2 months (95% CI, 3.8-5.9) in the lenvatinib arm vs 4 months (95% CI, 2.7-5.4) in the placebo arm (hazard ratio [HR] 0.91; 95% CI, 0.71-1.16).

Median OS was 11.2 months (95% CI, 7.4-14.9) and 13.8 months (95% CI, 9.8-18.8) with lenvatinib and placebo, respectively (HR 1.25; 95% CI, 0.94-1.67); the 6-month OS rate was 63.6% for lenvatinib vs 70.7% for placebo.

Moreover, the overall response rate was 31.2% in the lenvatinib arm and 26.5% in the placebo arm.

The safety profile of lenvatinib plus pembrolizumab was consistent with that seen in previous studies with no new safety signals. Treatment-related adverse events occurred in 86.9% of patients in the lenvatinib group and 67.1% of those in the placebo group.

Grade 3 to 5 treatment-related adverse events occurred in 50% and 27.9% of patients in the lenvatinib and placebo arms, respectively, and death occurred in 2.8% and 0.5%, respectively.

Study authors concluded that “the benefit/risk ratio for pembrolizumab plus lenvatinib was not considered positive vs pembrolizumab plus placebo in platinum-ineligible patients with advanced [urothelial carcinoma]. Antitumor activity of pembrolizumab plus placebo was similar to what has been reported in previous studies, and pembrolizumab monotherapy remains standard of care as first-line therapy […].

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Loriot Y, Grivas P, Wit RD, et al. First-line pembrolizumab (pembro) with or without lenvatinib (lenva) in patients with advanced urothelial carcinoma (LEAP-011): A phase 3, randomized, double-blind study. Presented at: ASCO-GU 2022; February 17-19, 2022; Abstract 432.

This article originally appeared on MPR