2024-01-12 12:23:52
The study included patients with a PD-L1 tumor proportion score of 1% or greater and no targetable mutations. Despite seeing a prolongation in progression-free survival and a higher objective response rate with lenvatinib, there were no significant improvements in overall survival compared to placebo (14.1 vs. 16.4 months). Importantly, lenvatinib use was associated with a marked increase in toxicity, resulting in death in 5.2% of patients. Taking into account the unfavorable benefit-risk ratio, the incorporation 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:
Patients with previously untreated stage IV non-small cell lung cancer (NSCLC) with a programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥1% and no EGFR/ROS1/ALK aberrations treatable, were randomly assigned in a 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. The primary endpoints were progression-free survival (RECIST version 1.1) and overall survival (OS). We report the results of a prespecified, non-binding futility analysis of OS performed in the 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, 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. placebo plus pembrolizumab (HR, 1.10 [IC del 95%, 0.87-1.39]; P=0.79744 [criterio de futilidad cumplido]). 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 [IC del 95%, 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 with placebo plus pembrolizumab. Pembrolizumab monotherapy remains an approved treatment option in many regions for first-line metastatic non-small cell lung cancer with a PD-L1 tumor proportion score ≥1% without alterations in EGFR/ALK.
Fuente: BioPress
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#Pembrolizumab #Lenvatinib #FirstLine #Metastatic #NonSmall #Cell #Lung #Cancer
