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

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

summary

Introduction:

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

Methods:

Patients with previously untreated stage IV non-small cell lung cancer (NSCLC) with programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥1% and treatable EGFR/ROS1/ALK abnormalities were randomized. were assigned. 1:1 ratio to receive 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 pre-specified, non-binding futility analysis of OS performed in a fourth independent Data and Safety Monitoring Committee (DMC) review (futility cutoff: one-way P < 0.4960).

Results:

623 patients were randomized. At a median follow-up of 15.9 months, the 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 criteria met)). Median (95% CI) progression-free survival was 6.6 (6.1-8.2) months versus 4.2 (4.1-6.2) months, respectively (HR, 0.78 (95% CI, 0.64-0.95%). Grade 3-5 treatment-related adverse Events occurred in 57.9% of patients (179/309) versus 24.4% (76/312).As recommended by the Data Monitoring Committee, the study was unblinded and lenvatinib and placebo were discontinued.

Conclusion:

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

Source: Biopress