Lazertinib Versus Osimertinib in Previously Untreated EGFR-Mutant Advanced NSCLC: A Randomized, Double-Blind, Exploratory Analysis From MARIPOSA

作者：Se-Hoon Lee, Shun Lü, Hidetoshi Hayashi, Enriqueta Felip, Alexander I. Spira, Nicolas Girard, Yu Jung Kim, Yurii Ostapenko, Pongwut Danchaivijitr, Baogang Liu, Adlinda Alip, Ernesto Korbenfeld, Josiane Mourão Dias, Ki Hyeong Lee, Hailin Xiong, Soon Hin How, Ying Cheng, Gee‐Chen Chang, James C. Yang, Benjamin Besse, Michael Thomas, Sujay Shah, Mahadi Baig, Joshua C. Curtin, Jiarui Zhang, John Xie, Tao Sun, Seema Sethi, Miao Wang, E. Fennema, Mahesh Daksh, Mariah Ennis, Joshua Bauml, Byoung Chul Cho · 发表于：Journal of Thoracic Oncology · 年份：2025 · DOI：10.1016/j.jtho.2025.06.030 · 被引用次数：13 · 研究领域：Lung Cancer Treatments and Mutations、HER2/EGFR in Cancer Research、Advanced Breast Cancer Therapies

INTRODUCTION: Lazertinib is a central nervous system-penetrant, third-generation EGFR tyrosine kinase inhibitor (TKI) that was selected for combination with amivantamab due to its relatively low rates of wild-type EGFR toxicities. In the phase 3 MARIPOSA study, amivantamab plus lazertinib (amivantamab-lazertinib) significantly improved progression-free survival (PFS; p < 0.001) versus osimertinib in participants with treatment-naive EGFR-mutant advanced NSCLC. A lazertinib monotherapy arm was included to assess the contribution of components in the combination. This is the first randomized, double-blind comparison of two third-generation EGFR TKIs, lazertinib and osimertinib. METHODS: In MARIPOSA, 1074 participants were randomized 2:2:1 to receive amivantamab-lazertinib (n = 429), osimertinib monotherapy (n = 429), or lazertinib monotherapy (n = 216). This exploratory analysis compared the efficacy and safety of lazertinib and osimertinib. RESULTS: At a median follow-up of 22.0 months, median PFS was 18.5 months for lazertinib versus 16.6 months for osimertinib (hazard ratio = 0.98, 95% confidence interval: 0.79-1.22; p = 0.86). PFS results were comparable between arms among predefined subgroups. Among participants with measurable disease at baseline, objective response rate was 83% for lazertinib versus 85% for osimertinib, with a median duration of response among confirmed responders of 16.6 months versus 16.8 months, respectively. Median overall survival was not reached fo...