Overall Survival with Amivantamab-Lazertinib in EGFR-Mutated Advanced NSCLC
Mené sur 429 patients atteints d'un cancer du poumon non à petites cellules avec mutation EGFR et de stade localement avancé ou métastatique (durée médiane : 37,8 mois), cet essai de phase III évalue l'efficacité, du point de vue de la survie globale, d'un traitement de première ligne combinant amivantamab et lazertinib
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.)
New England Journal of Medicine , résumé, 2025