Overall Survival with Amivantamab-Lazertinib in -Mutated Advanced NSCLC.
Journal
The New England journal of medicine
Journal Volume
393
Journal Issue
17
Start Page
1681
End Page
1693
ISSN
1533-4406
Date Issued
2025-10-30
Author(s)
Lu, Shun
Hayashi, Hidetoshi
Felip, Enriqueta
Spira, Alexander I
Girard, Nicolas
Kim, Yu Jung
Lee, Se-Hoon
Ostapenko, Yurii
Danchaivijitr, Pongwut
Liu, Baogang
Alip, Adlinda
Korbenfeld, Ernesto
Mourão Dias, Josiane
Besse, Benjamin
Passaro, Antonio
Lee, Ki-Hyeong
Xiong, Hailin
How, Soon-Hin
Cheng, Ying
Chang, Gee-Chen
Yoshioka, Hiroshige
Thomas, Michael
Nguyen, Danny
Ou, Sai-Hong Ignatius
Mukhedkar, Sanjay
Prabhash, Kumar
D'Arcangelo, Manolo
Alatorre-Alexander, Jorge
Vázquez Limón, Juan Carlos
Alves, Sara
Stroyakovskiy, Daniil
Peregudova, Marina
Şendur, Mehmet Ali Nahit
Yazici, Ozan
Califano, Raffaele
Gutiérrez Calderón, Vanesa
de Marinis, Filippo
Kim, Sang-We
Gadgeel, Shirish M
Owen, Scott
Xie, John
Sun, Tao
Mehta, Jaydeep
Venkatasubramanian, Raja
Ennis, Mariah
Fennema, Elizabeth
Daksh, Mahesh
Roshak, Amy
Man, Julie
Knoblauch, Roland E
Bauml, Joshua M
Baig, Mahadi
Shah, Sujay
Sethi, Seema
Cho, Byoung Chul
Abstract
Previous results from this phase 3 trial showed that progression-free survival among participants with previously untreated (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.
We randomly assigned, in a 2:2:1 ratio, participants with previously untreated -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.
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.
Amivantamab-lazertinib led to significantly longer overall survival among participants with previously untreated -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.).
Type
journal article