Overall Survival with Amivantamab-Lazertinib in EGFR-Mutated Advanced NSCLC

BACKGROUND: Previous results from this phase 3 trial showed that progression-free survival among participants with previously untreated EGFR (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: We randomly assigned, in a 2:2:1 ratio, participants with previously untreated EGFR-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: Amivantamab-lazertinib led to significantly longer overall survival among participants with previously untreated EGFR-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.).

• Yang, J. C.
• Lu, S.
• Hayashi, H.
• Felip, E.
• Spira, A. I.
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• Kim, Y. J.
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• Ostapenko, Y.
• Danchaivijitr, P.
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• Korbenfeld, E.
• Mourão Dias, J.
• Besse, B.
• Passaro, A.
• Lee, K. H.
• Xiong, H.
• How, S. H.
• Cheng, Y.
• Chang, G. C.
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• Thomas, M.
• Nguyen, D.
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• Mukhedkar, S.
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• D'Arcangelo, M.
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• Vázquez Limón, J. C.
• Alves, S.
• Stroyakovskiy, D.
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• Califano, R.
• Guti
• de Marinis, F.
• Kim, S. W.
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• Venkatasubramanian, R.
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• Sethi, S.
• Cho, B. C.