LEAP-008: Lenvatinib Plus Pembrolizumab for Metastatic NSCLC That Has Progressed After an Anti–Programmed Cell Death Protein 1 or Anti–Programmed Cell Death Ligand 1 Plus Platinum Chemotherapy
Natasha B. Leighl, Luis Paz‐Ares, Delvys Rodríguez‐Abreu, Rina Hui, Sofia Baka, Frédéric Bigot, Makoto Nishio, Alexey Smolin, Samreen Ahmed, Adam J. Schoenfeld, Sameh Daher, Diego Cortinovis, Vincenzo Di Noia, Helena Linardou, Justin F. Gainor, Corina E. Dutcus, Chinyere E. Okpara, Xuan Deng, Debra Kush, Ashwini Arunachalam, Andrew Song, Byoung Chul Cho
Abstract
BACKGROUND: LEAP-008 (NCT03976375) was an open-label, randomized, phase 3 study of lenvatinib plus pembrolizumab versus docetaxel for metastatic NSCLC that progressed on anti‒programmed cell death protein 1 or anti‒programmed cell death ligand 1 therapy and platinum-containing chemotherapy. METHODS: every 3 weeks, or once-daily lenvatinib 24 mg. Primary end points were overall survival (OS) and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 by central review. The superiority of lenvatinib plus pembrolizumab versus docetaxel was assessed at interim analysis 2 for PFS and final analysis for OS. RESULTS: Participants (N = 422) were randomized to lenvatinib plus pembrolizumab (n = 185), docetaxel (n = 189), or lenvatinib monotherapy (n = 48). The median (95% confidence interval [CI]) PFS was 5.6 (4.2‒6.5) months with lenvatinib plus pembrolizumab and 4.2 (3.2‒5.2) months with docetaxel (hazard ratio, 0.89 [95% CI: 0.70‒1.12]; p = 0.164). The median (95% CI) OS was 11.3 (9.4‒13.2) versus 12.0 (9.6‒13.7) months (hazard ratio, 0.98 [95% CI: 0.78‒1.23]; p = 0.434). Rates of treatment-related adverse events were 91.7%, 91.0%, and 89.4% with lenvatinib plus pembrolizumab, docetaxel, and lenvatinib, respectively; the rates of grade 3 to 5 treatment-related adverse events were 59.7%, 48.6%, and 57.4%. Health-related quality of life scores were similar between treatment arms. CONCLUSION: Lenvatinib plus pembrolizumab did not improve efficacy versus docetaxel in participants with stage IV NSCLC that progressed on anti‒programmed cell death protein 1 or anti-programmed cell death ligand 1 therapy and platinum-containing chemotherapy. There were no unexpected safety signals. More effective therapies are needed for this patient population.