Pembrolizumab With or Without Lenvatinib for First-Line Metastatic NSCLC With Programmed Cell Death-Ligand 1 Tumor Proportion Score of at least 1% (LEAP-007): A Randomized, Double-Blind, Phase 3 Trial.

Autor:	Yang JC; Department of Oncology, National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan, Republic of China. Electronic address: chihyang@ntu.edu.tw., Han B; Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China., De La Mora Jiménez E; Instituto Jalisciense de Cancerologia, Guadalajara, Mexico., Lee JS; Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea., Koralewski P; Ludwik Rydygier Memorial Specialist Hospital, Krakow, Poland., Karadurmus N; Gulhane Training and Research Hospital, Ankara, Turkey., Sugawara S; Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Miyagi, Japan., Livi L; Department of Experimental and Biomedical Sciences Mario Serio, University of Florence and Radiation Oncology Unit, Oncology Department, Azienda Ospedaliero Universitaria Careggi, Florence, Italy., Basappa NS; Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada., Quantin X; IRCM, INSERM, University of Montpellier, ICM, Montpellier, France., Dudnik J; Soroka Medical Center, Beer-Sheva, Israel., Ortiz DM; Fundacion Centro de Investigacion Clinica CIC, Medellin, Colombia., Mekhail T; Advent Health Cancer Institute, Orlando, Florida., Okpara CE; Eisai Ltd., Hatfield, United Kingdom., Dutcus C; Eisai Inc., Nutley, New Jersey., Zimmer Z; Merck & Co., Inc., Rahway, New Jersey., Samkari A; Merck & Co., Inc., Rahway, New Jersey., Bhagwati N; Merck & Co., Inc., Rahway, New Jersey., Csőszi T; Hetenyi Geza Korhaz, Szolnok, Hungary.
Jazyk:	angličtina
Zdroj:	Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer [J Thorac Oncol] 2024 Jun; Vol. 19 (6), pp. 941-953. Date of Electronic Publication: 2023 Dec 29.
DOI:	10.1016/j.jtho.2023.12.023
Abstrakt:	Introduction: Lenvatinib plus pembrolizumab was found to have antitumor activity and acceptable safety in previously treated metastatic NSCLC. We evaluated first-line lenvatinib plus pembrolizumab versus placebo plus pembrolizumab in metastatic NSCLC in the LEAP-007 study (NCT03829332/NCT04676412). Methods: Patients with previously untreated stage IV NSCLC with programmed cell death-ligand 1 tumor proportion score of at least 1% without targetable EGFR/ROS1/ALK aberrations were randomized 1:1 to lenvatinib 20 mg or placebo once daily; all patients received pembrolizumab 200 mg every 3 weeks for up to 35 cycles. Primary end points were progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 and overall survival (OS). We report results from a prespecified nonbinding futility analysis of OS performed at the fourth independent data and safety monitoring committee review (futility bound: one-sided p < 0.4960). Results: A total of 623 patients were randomized. At median follow-up of 15.9 months, median (95% confidence interval [CI]) OS was 14.1 (11.4‒19.0) months in the lenvatinib plus pembrolizumab group versus 16.4 (12.6‒20.6) months in the placebo plus pembrolizumab group (hazard ratio = 1.10 [95% CI: 0.87‒1.39], p = 0.79744 [futility criterion met]). Median (95% CI) PFS was 6.6 (6.1‒8.2) months versus 4.2 (4.1‒6.2) months, respectively (hazard ratio = 0.78 [95% CI: 0.64‒0.95]). Grade 3 to 5 treatment-related adverse events occurred in 57.9% of patients (179 of 309) versus 24.4% (76 of 312). Per data and safety monitoring committee recommendation, the study was unblinded and lenvatinib and placebo were discontinued. Conclusions: Lenvatinib plus pembrolizumab did not have a favorable benefit‒risk profile versus placebo plus pembrolizumab. Pembrolizumab monotherapy remains an approved treatment option in many regions for first-line metastatic NSCLC with programmed cell death-ligand 1 tumor proportion score of at least 1% without EGFR/ALK alterations. Competing Interests: Disclosure Dr. Yang reports receiving funding to institution for serving on advisory or consultancy services for Daiichi Sankyo, Eli Lilly, Merck KGaA, Darmstadt, Germany, Merck Sharp & Dohme, Novartis, Roche, Genentech, Takeda Oncology, Yuhan Pharmaceuticals, Janssen Pharmaceuticals, Puma Technology, Gilead Sciences Inc., GlaxoSmithKline, BeiGene, Blueprint Medicines Corporation, Regeneron Pharmaceutical, and Taiho Pharmaceutical; receiving grant from Roche/Genentech; and having advisory or consultancy services from Ono Pharmaceuticals and Pfizer. Dr. Han reports receiving study funding to the institution from Eisai Inc., Nutley, New Jersey, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, to support study conduct. Dr. Jiménez reports receiving study funding to the institution from Eisai Inc., Nutley, New Jersey, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, to support study conduct. Dr. Lee reports receiving study funding to the institution from Eisai Inc., Nutley, New Jersey, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, to support study conduct. Dr. Koralewski reports receiving study funding to the institution from Eisai Inc., Nutley, New Jersey, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, to support study conduct. Dr. Karadurmus reports receiving study funding to the institution from Eisai Inc., Nutley, New Jersey, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, to support study conduct. Dr. Sugawara reports receiving grants or contracts to their institution from AnHeart, AstraZeneca, Chugai Pharma, MSD, Daiichi Sankyo, Bristol-Myers Squibb, Nippon Boehringer Ingelheim, Ono Pharmaceuticals, AbbVie, Amgen, Taiho Pharmaceutical, Takeda, and Clinipace; payment or honoraria from AstraZeneca, Chugai Pharma, Ono Pharmaceutical, Bristol-Myers Squibb, MSD, Nippon Boehringer Ingelheim, Pfizer, Taiho Pharmaceutical, Eli Lilly and Company, Novartis, Kyowa Kirin, Takeda, Nippon Kayaku, Merck Biopharma Japan, Amgen, AbbVie, Otsuka, Thermo Fisher Scientific, and Towa Pharmaceutical. Dr. Livi reports receiving study funding to the institution from Eisai Inc., Nutley, New Jersey, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, to support study conduct. Dr. Basappa reports receiving grants or contracts from Ipsen; receiving payment or honoraria from Bayer, Astellas, and Janssen; receiving support for attending meetings from Eisa, Ipsen, and Janssen; having participation on data safety monitoring board or advisory board with Eisai, Ipsen, Pfizer, Bristol-Myers Squibb, Roche, Janssen, AstraZeneca, EMD Serono, Bayer, Astellas, and MSD. Dr. Quantin reports receiving payment or honoraria to their institution from Sanofi, Bristol-Myers Squibb, and AstraZeneca; receiving support for attending meetings from Janssen Cilag, Sanofi, and Pfizer; and having participation on data safety monitoring board or advisory board with Bristol-Myers Squibb. Dr. Dudnik reports receiving study funding to the institution from Eisai Inc., Nutley, New Jersey, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, to support study conduct. Dr. Moran reports receiving support for present manuscript from MSD; grants or contracts from Abbott; consulting fees from Bristol-Myers Squibb and MSD; honoraria from Bristol-Myers Squibb, MSD, AstraZeneca, GlaxoSmithKline, Novartis, and Bayer; support for attending meetings from Tecnofarma, Roche, Pfizer, Bayer, and Janssen; and having participation on data safety monitoring board or advisory board with MSD. Dr. Mekhail reports receiving payment for speakers bureau from MSD. Drs. Okpara and Dutcus are employees of Eisai Ltd., Hatfield, UK. Drs. Zimmer, Samkari, and Bhagwati are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, and own stock in Merck & Co., Inc., Rahway, New Jersey. Dr. Csőszi reports receiving study funding to the institution from Eisai Inc., Nutley, New Jersey, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, to support study conduct. (Copyright © 2024 Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, The Author(s). Published by Elsevier Inc. All rights reserved.)
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