Pembrolizumab with or without lenvatinib for first-line metastatic non-small cell lung cancer

Patients with a PD-L1 tumor fraction score of 1% or higher and no targetable mutations were included in the study. Despite improved progression-free survival and higher objective response rates with lenvatinib, there was no significant improvement in overall survival compared with placebo (14.1 vs. 16.4 months). Importantly, lenvatinib was associated with a marked increase in toxicity, resulting in death in 5.2% of patients. Given the unfavorable benefit-risk ratio, inclusion of lenvatinib in this clinical context is not recommended.



Lenvatinib in combination with pembrolizumab demonstrated antitumor activity and acceptable safety in patients with previously treated metastatic non-small cell lung cancer. In the LEAP-007 trial (NCT03829332/NCT04676412), we evaluated first-line treatment with lenvatinib plus pembrolizumab versus placebo plus pembrolizumab in patients with metastatic non-small cell lung cancer.


Patients with previously untreated stage IV non-small cell lung cancer (NSCLC) with a programmed cell death ligand 1 (PD-L1) tumor fraction score (TPS) ≥1% and without treatable EGFR/ROS1/ALK aberrations were randomized to a ratio of 1 :1 for lenvatinib 20 mg or placebo once daily; all patients received pembrolizumab 200 mg every 3 weeks for up to 35 cycles. Primary endpoints were progression-free survival (RECIST version 1.1) and overall survival (OS). We report the results of a prespecified, nonbinding OS futility analysis conducted in the fourth independent Data and Safety Monitoring Committee (DMC) review (futility cutoff: one-sided P < 0.4960).


623 patients were randomized. At a median follow-up of 15.9 months, median (95% CI) overall survival was 14.1 (11.4–19.0) months in the lenvatinib plus pembrolizumab group compared with 16.4 (12.6–20.6) months in the lenvatinib plus pembrolizumab group. plus pembrolizumab (HR 1.10 (95% CI 0.87–1.39); P=0.79744 (futility met)). Median (95% CI) progression-free survival was 6.6 (6.1-8.2) months vs 4.2 (4.1-6.2) months, respectively (HR 0.78 (95% CI 0.64 -0.95)). Treatment-related grade 3-5 adverse events were observed in 57.9% of patients (179/309) versus 24.4% (76/312). As recommended by the Data Monitoring Committee, the study was open-label and lenvatinib and placebo were discontinued.


The combination of lenvatinib and pembrolizumab did not show a favorable benefit-risk profile compared with placebo and pembrolizumab. Pembrolizumab monotherapy remains an approved treatment option in many regions for first-line metastatic non-small cell lung cancer with PD-L1 tumor proportion ≥1% without EGFR/ALK alterations.

Source: BioPress

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