Overall Survival with Amivantamab–Lazertinib in <i>EGFR</i> -Mutated Advanced NSCLC
James Chih‐Hsin Yang, Shun Lu, Hidetoshi Hayashi, Enriqueta Felip, Alexander I. Spira, Nicolas Girard, Yu Jung Kim, Se-Hoon Lee, Yurii Ostapenko, Pongwut Danchaivijitr, Baogang Liu, Adlinda Alip, Ernesto Korbenfeld, Josiane Mourão Dias, Benjamin Besse, Antonio Passaro, Ki-Hyeong Lee, Hailin Xiong, Soon-Hin How, Ying Cheng, Gee-Chen Chang, Hiroshige Yoshioka, Michael Thomas, Danny T. Nguyen, Sai‐Hong Ignatius Ou, Sanjay Mukhedkar, Kumar Prabhash, M. D’Arcangelo, Jorge Alatorre-Alexander, Juan Carlos Vázquez Limón, Sara Alves, Daniil Stroyakovskiy, Marina Peregudova, Mehmet Alı Nahıt Şendur, Ozan Yazıcı, Raffaele Califano, Vanesa Gutiérrez Calderón, Filippo de Marinis, Sang‐We Kim, Shirish M. Gadgeel, Scott Owen, John Xie, Tao Sun, Jaydeep Mehta, Raja Venkatasubramanian, Mariah Ennis, E. Fennema, Mahesh Daksh, Amy Roshak, Julie Man, Roland E. Knoblauch, Joshua Bauml, Mahadi Baig, Sujay Shah, Seema Sethi, Byoung Chul Cho
Abstract
BACKGROUND: (epidermal growth factor receptor)-mutated advanced non-small-cell lung cancer (NSCLC) was significantly improved with amivantamab-lazertinib as compared with osimertinib. Results of the protocol-specified final overall survival analysis in this trial have not been reported. METHODS: -mutated (exon 19 deletion or L858R substitution), locally advanced or metastatic NSCLC to receive amivantamab-lazertinib, osimertinib, or lazertinib. Overall survival (assessed in an analysis of the time from randomization to death from any cause) in the amivantamab-lazertinib group as compared with the osimertinib group was a key secondary end point. Additional end points included safety. RESULTS: A total of 429 participants each were assigned to receive amivantamab-lazertinib or osimertinib. Over a median follow-up of 37.8 months, amivantamab-lazertinib led to significantly longer overall survival than osimertinib (hazard ratio for death, 0.75; 95% confidence interval, 0.61 to 0.92; P = 0.005); 3-year overall survival was 60% and 51%, respectively. At the clinical cutoff date, 38% of participants in the amivantamab-lazertinib group and 28% in the osimertinib group were still receiving the assigned treatment. Adverse events of grade 3 or higher were more common with amivantamab-lazertinib (in 80% of participants) than with osimertinib (in 52%), particularly skin-related events, venous thromboembolism, and infusion-related events; these findings were consistent with the established safety profile of each treatment. No new safety signals were observed with additional follow-up. CONCLUSIONS: -mutated advanced NSCLC than osimertinib but was associated with an increased risk of adverse events of grade 3 or higher. (Funded by Janssen Research and Development; MARIPOSA ClinicalTrials.gov number, NCT04487080.).