Amivantamab plus Lazertinib in Previously Untreated EGFR -Mutated Advanced NSCLC

• Published in: The New England journal of medicine
• Main Authors: Cho, Byoung C, Lu, Shun, Felip, Enriqueta, Spira, Alexander I, Girard, Nicolas, Lee, Jong-Seok, Lee, Se-Hoon, Ostapenko, Yurii, Danchaivijitr, Pongwut, Liu, Baogang, Alip, Adlinda, Korbenfeld, Ernesto, Mourão Dias, Josiane, Besse, Benjamin, Lee, Ki-Hyeong, Xiong, Hailin, How, Soon-Hin, Cheng, Ying, Chang, Gee-Chen, Yoshioka, Hiroshige, Yang, James C-H, Thomas, Michael, Nguyen, Danny, Ou, Sai-Hong I, Mukhedkar, Sanjay, Prabhash, Kumar, D'Arcangelo, Manolo, Alatorre-Alexander, Jorge, Vázquez Limón, Juan C, Alves, Sara, Stroyakovskiy, Daniil, Peregudova, Marina, Şendur, Mehmet A N, Yazici, Ozan, Califano, Raffaele, Gutiérrez Calderón, Vanesa, de Marinis, Filippo, Passaro, Antonio, Kim, Sang-We, Gadgeel, Shirish M, Xie, John, Sun, Tao, Martinez, Melissa, Ennis, Mariah, Fennema, Elizabeth, Daksh, Mahesh, Millington, Dawn, Leconte, Isabelle, Iwasawa, Ryota, Lorenzini, Patricia, Baig, Mahadi, Shah, Sujay, Bauml, Joshua M, Shreeve, S Martin, Sethi, Seema, Knoblauch, Roland E, Hayashi, Hidetoshi
• Format: Journal Article
• Language: English
• Published: United States 26.06.2024
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa2403614

Amivantamab plus lazertinib (amivantamab-lazertinib) has shown clinically meaningful and durable antitumor activity in patients with previously untreated or osimertinib-pretreated (epidermal growth factor receptor)-mutated advanced non-small-cell lung cancer (NSCLC). In a phase 3, international, randomized trial, we assigned, in a 2:2:1 ratio, patients with previously untreated -mutated (exon 19 deletion or L858R), locally advanced or metastatic NSCLC to receive amivantamab-lazertinib (in an open-label fashion), osimertinib (in a blinded fashion), or lazertinib (in a blinded fashion, to assess the contribution of treatment components). The primary end point was progression-free survival in the amivantamab-lazertinib group as compared with the osimertinib group, as assessed by blinded independent central review. Overall, 1074 patients underwent randomization (429 to amivantamab-lazertinib, 429 to osimertinib, and 216 to lazertinib). The median progression-free survival was significantly longer in the amivantamab-lazertinib group than in the osimertinib group (23.7 vs. 16.6 months; hazard ratio for disease progression or death, 0.70; 95% confidence interval [CI], 0.58 to 0.85; P<0.001). An objective response was observed in 86% of the patients (95% CI, 83 to 89) in the amivantamab-lazertinib group and in 85% of those (95% CI, 81 to 88) in the osimertinib group; among patients with a confirmed response (336 in the amivantamab-lazertinib group and 314 in the osimertinib group), the median response duration was 25.8 months (95% CI, 20.1 to could not be estimated) and 16.8 months (95% CI, 14.8 to 18.5), respectively. In a planned interim overall survival analysis of amivantamab-lazertinib as compared with osimertinib, the hazard ratio for death was 0.80 (95% CI, 0.61 to 1.05). Predominant adverse events were -related toxic effects. The incidence of discontinuation of all agents due to treatment-related adverse events was 10% with amivantamab-lazertinib and 3% with osimertinib. Amivantamab-lazertinib showed superior efficacy to osimertinib as first-line treatment in -mutated advanced NSCLC. (Funded by Janssen Research and Development; MARIPOSA ClinicalTrials.gov number, NCT04487080.).