Amivantamab plus Lazertinib in Previously Untreated -Mutated Advanced NSCLC.
Journal
The New England journal of medicine
Journal Volume
391
Journal Issue
16
Start Page
1486
End Page
1498
ISSN
1533-4406
Date Issued
2024-10-24
Author(s)
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
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
Abstract
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.).
SDGs
Type
journal article