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

The study included patients with a PD-L1 tumor ratio score of 1% or higher and no targetable mutation. Despite longer progression-free survival and higher objective response rates seen with lenvatinib, there was no significant improvement in overall survival compared to 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 addition of lenvatinib is not recommended in this clinical context.

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:

Randomized 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 no treatable EGFR/ROS1/ALK aberrations. Was formally assigned. a 1:1 ratio to receive lenvatinib 20 mg or placebo once daily; All patients received 200 mg pembrolizumab every 3 weeks for up to 35 cycles. The 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 conducted at the fourth independent data and safety monitoring committee (DMC) review (futility cutoff: one-way P < 0.4960).

Result:

623 patients were randomized. At a median follow-up of 15.9 months, the median (95% CI) overall survival in the lenvatinib plus pembrolizumab group was 14.1 (11.4-19.0) months, compared with 16.4 (12.6-20.6) months in the lenvatinib plus pembrolizumab group. placebo 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 were observed in 57.9% of patients (179/309) versus 24.4% (76/312). As recommended by the Data Monitoring Committee, the study was unblinded and the use of lenvatinib and placebo was discontinued.

conclusion:

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

Source: Biopress