As reported in the Journal of Clinical Oncology by Licitra et al, the phase III LEAP-010 trial showed an improved objective response rate and progression-free survival—but not overall survival—with the addition of first-line lenvatinib to pembrolizumab in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) and a PD-L1 combined positive score (CPS) ≥ 1.
Study Details
In the international double-blind trial, 511 patients were randomly assigned between March 2020 and May 2023 to receive lenvatinib at 20 mg once daily (n = 256) or placebo once daily (n = 255) both with pembrolizumab at 200 mg every 3 weeks for ≤ 35 cycles. The primary endpoints were objective response rate, progression-free survival, and overall survival. As prespecified, objective response rate and progression-free survival were analyzed at first interim analysis (IA1; data cutoff = July 2022) and overall survival was analyzed at IA2 (data cutoff = May 2023).
Key Findings
Median times from random assignment to data cutoff were 11.5 months for IA1 and 21.3 months for IA2.
At IA1, median progression-free survival was 6.2 months in the lenvatinib plus pembrolizumab group vs 2.8 months in the placebo plus pembrolizumab group (hazard ratio [HR] = 0.64, 95% confidence interval [CI] = 0.50–0.81, P = .0001040). Objective response rates were 46.1% vs 25.4% (difference = 20.2%, 95% CI = 10.5%–29.6%, P = .0000251).
Subsequent anticancer therapy was administered to 91 patients (35.5%) in the lenvatinib plus pembrolizumab group and 114 patients (44.7%) in the placebo plus pembrolizumab group. At IA2, median overall survival was 15.0 months in the lenvatinib plus pembrolizumab group vs 17.9 months in the placebo plus pembrolizumab group (HR = 1.15, 95% CI = 0.91–1.45, P = .882).
Adverse events of grade ≥ 3 occurred in 210 (82.7%) patients in the lenvatinib plus pembrolizumab group vs 119 (47.0%) in the placebo plus pembrolizumab group. The most common were hypertension (26.0%), pneumonia (9.1%), and anemia (8.3%) in the lenvatinib plus pembrolizumab group, and anemia and pneumonia (both 4.0%) in the placebo plus pembrolizumab group. Adverse events led to the discontinuation of any study medication in 43.7% vs 15.0% of patients. Treatment-related deaths occurred in seven patients in the lenvatinib plus pembrolizumab group (three from tumor hemorrhage, two from upper gastrointestinal hemorrhage, one from pneumonia, and one from cardiac arrest) and three patients in the placebo plus pembrolizumab group (one from autoimmune lung disease, one from tumor hemorrhage, and one from acute left ventricle failure).
The investigators concluded: “In participants with PD-L1 CPS ≥ 1 recurrent or metastatic HNSCC, first-line lenvatinib plus pembrolizumab significantly improved [objective response rate and progression-free survival], but not [overall survival], compared with placebo plus pembrolizumab. The safety profile was consistent with published data.”
Lisa Licitra, MD, of Fondazione IRCCS Istituto Nazionale dei Tumori and University of Milan, Italy, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by Eisai Inc. and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co. Inc. For full disclosures of the study authors, visit ascopubs.org.
