Hidetoshi Hayashi, Byoung Chul Cho, Yu Jung Kim, Se-Hoon Lee, Pongwut Danchaivijitr, Adlinda Alip, Hailin Xiong, Soon-Hin How, Gee-Chen Chang, James Chih-Hsin Yang, Yuta Yamanaka, Mehmet Ali Nahit Şendur, Kumar Prabhash, Koichi Azuma, Alianu Akawung, E. Fennema, Xiaodan Tang, Sujay Shah, Seema Sethi, Shun Lu
BACKGROUND: Approximately 60 % of lung cancer cases occur in Asia, indicating an epidemiological disparity and need for effective therapies. Amivantamab-lazertinib is approved for first-line EGFR-mutated advanced non-small cell lung cancer (NSCLC) in many countries. In the protocol-specified final overall survival (OS) analysis of MARIPOSA (NCT04487080), amivantamab-lazertinib showed a statistically significant and clinically meaningful improvement in OS versus osimertinib (HR, 0.75; P = 0.005) among all participants. We evaluated OS for amivantamab-lazertinib versus osimertinib in Asian participants. PATIENTS AND METHODS: Participants with previously untreated EGFR-mutated, locally advanced/metastatic NSCLC were randomized 2:2:1 to receive amivantamab-lazertinib, osimertinib, or lazertinib (for evaluating contribution of components). Self-identified Asian race was a stratification factor. OS was a key secondary endpoint. RESULTS: Of 1074 randomized participants, 629 self-identified as Asian (amivantamab-lazertinib:250; osimertinib:251; lazertinib:128). At a median follow-up of 38.7 months, amivantamab-lazertinib significantly prolonged OS versus osimertinib among Asian participants. Median OS was not reached (NR; 95 % CI, NR-NR) for amivantamab-lazertinib versus 38.4 months (95 % CI, 35.1-NR) for osimertinib (HR, 0.74; 95 % CI, 0.56-0.97; nominal P = 0.026). Assuming exponential distribution of OS in both arms, amivantamab-lazertinib is projected to prolong median OS among Asian participants by > 12 months versus osimertinib. At 36 months, 61 % and 53 % were alive in the amivantamab-lazertinib and osimertinib arms. Safety profile was consistent with the overall population. CONCLUSIONS: Consistent with the overall population, amivantamab-lazertinib significantly improved OS versus osimertinib among Asian participants with previously untreated EGFR-mutated advanced NSCLC, making it the first regimen to improve survival among Asian patients.