Findings from the LEAP-011 study were presented during the general session, Novel Therapies and Their Toxicities in Bladder Cancer, at the 2022 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium. Researchers, led by Yohann Loriot, Phd, MD, compared pembrolizumab and lenvatinib against pembrolizumab and placebo for locally advanced or metastatic urothelial carcinoma (UC), and observed that “the benefit/risk ratio for pembro + lenva was not considered positive vs pembro + placebo in platinum-ineligible pts with advanced UC.”
The study randomized 441 patients with locally advanced or metastatic UC who were cisplatin-ineligible with PD-L1 expression, or were ineligible for platinum-based chemotherapy, to receive pembrolizumab 200mg intravenous (IV) Q3W for 35 cycles max (approx. 2 years) and either daily oral lenvatinib 20mg (n = 218) or a placebo (n = 223). The study’s primary endpoints were progression-free survival (PFS), and overall survival (OS), with objective response rate (ORR) as the secondary endpoint—all based on Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
According to the report, the median treatment duration was 3.8 months for the intervention group (range: 0.0-20.7) and 3.4 months for the placebo group (range: 0.0 22.0). In the intervention group, the median PFS was 4.2 months (95% confidence interval [CI], 3.8 5.9), while the placebo group’s PFS was 4.0 months (hazard ratio [HR] = 0.91; 95% CI, 0.71-1.16). The median OS for pembrolizumab with lenvatinib and pembrolizumab with placebo was 11.2 months (95% CI, 3.8-5.9) and 13.8 months (95% CI, 9.8-18.8), respectively (HR = 1.25; 95% CI, 0.94-1.67), with the placebo group having a higher OS rate at six months (70.7% vs. 63.6%). ORR did favor the intervention regimen over the placebo (31.2% vs. 26.5%), however, the rate of treatment-related adverse events (TRAEs) was higher in the intervention versus placebo group (86.9% vs. 67.1%).
While the safety profile of pembrolizumab with lenvatinib was consistent with previous studies, the head-to-head comparison did not find an effective improvement in clinical outcomes, according to Dr. Loriot and collaborators. They concluded that pembrolizumab monotherapy should remain the “standard of care as first-line therapy in platinum-ineligible pts with advanced UC.”