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

MARIPOSA Investigators

doi:10.1056/NEJMoa2503001

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

MARIPOSA Investigators

Department of Internal Medicine

National Taiwan University
Shanghai Jiao Tong University
Kindai University
Autonomous University of Barcelona
Fair-fax
Institut Curie
Université Paris-Saclay
Seoul National University
Zaporizhia Medical Academy of Post-Gradate Education Ministry of Health of Ukraine
Mahidol University
Harbin Medical University
University of Malaya
Hospital Británico de Buenos Aires
Hospital de Câncer de Barretos
Gustave Roussy
IRCCS Istituto Europeo di Oncologia - Milano
Chungbuk National University
Huizhou Municipal Central Hospital of Guangdong Province
International Islamic University Malaysia
Jilin Cancer Hospital
Chung Shan Medical University
Kansai Medical University
Heidelberg University
German Cancer Research Center
German Center for Lung Research
City of Hope National Med Center
University of California at Irvine
St John of God Health Care
Tata Memorial Hospital
Ospedale S. Maria delle Croci
Health Pharma Professional Research
Hospital Civil de Guadalajara
Instituto Português de Oncologia do Porto Francisco Gentil E.P.E.
Moscow City Oncology Hospital No. 62
Medical Center in Kolomenskoe
Yildirim Beyazit Universitesi
Gazi University
University of Manchester
Hospital Regional Universitario Carlos Haya
University of Ulsan
Henry Ford Health
McGill University
Johnson & Johnson

Research output: Contribution to journal › Article › peer-review

49 Scopus citations

Abstract

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 EGFRmutated (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.

Original language	English
Pages (from-to)	1681-1693
Number of pages	13
Journal	New England Journal of Medicine
Volume	393
Issue number	17
DOIs	https://doi.org/10.1056/NEJMoa2503001
State	Published - 30 Oct 2025

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Hematology/Oncology
Lung Cancer
Pulmonary/Critical Care
Pulmonary/Critical Care General
Treatments in Oncology

Access to Document

10.1056/NEJMoa2503001

Cite this

@article{f21c242a69ff4d6a8c8c40956951745a,

title = "Overall Survival with Amivantamab–Lazertinib in EGFR-Mutated Advanced NSCLC",

abstract = "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 EGFRmutated (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.",

keywords = "Hematology/Oncology, Lung Cancer, Pulmonary/Critical Care, Pulmonary/Critical Care General, Treatments in Oncology",

author = "\{MARIPOSA Investigators\} and Yang, \{James Chih Hsin\} and Shun Lu and Hidetoshi Hayashi and Enriqueta Felip and Spira, \{Alexander I.\} and Nicolas Girard and Kim, \{Yu Jung\} and Lee, \{Se Hoon\} and Yurii Ostapenko and Pongwut Danchaivijitr and Baogang Liu and Adlinda Alip and Ernesto Korbenfeld and Dias, \{Josiane Mour{\~a}o\} and Benjamin Besse and Antonio Passaro and Lee, \{Ki Hyeong\} and Hailin Xiong and How, \{Soon Hin\} and Ying Cheng and Chang, \{Gee Chen\} and Hiroshige Yoshioka and Michael Thomas and Danny Nguyen and Ou, \{Sai Hong Ignatius\} and Sanjay Mukhedkar and Kumar Prabhash and Manolo D{\textquoteright}Arcangelo and Jorge Alatorre-Alexander and Lim{\'o}n, \{Juan Carlos V{\'a}zquez\} and Sara Alves and Daniil Stroyakovskiy and Marina Peregudova and {\c S}endur, \{Mehmet Ali Na Hit\} and Ozan Yazici and Raffaele Califano and Calder{\'o}n, \{Vanesa Guti{\'e}rrez\} and \{de Marinis\}, Filippo and Kim, \{Sang We\} and Gadgeel, \{Shirish M.\} and Scott Owen and John Xie and Tao Sun and Jaydeep Mehta and Raja Venkatasubramanian and Mariah Ennis and Elizabeth Fennema and Mahesh Daksh and Amy Roshak and Julie Man",

note = "Publisher Copyright: Copyright {\textcopyright} 2025 Massachusetts Medical Society.",

year = "2025",

month = oct,

day = "30",

doi = "10.1056/NEJMoa2503001",

language = "English",

volume = "393",

pages = "1681--1693",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachussetts Medical Society",

number = "17",

}

TY - JOUR

T1 - Overall Survival with Amivantamab–Lazertinib in EGFR-Mutated Advanced NSCLC

AU - MARIPOSA Investigators

AU - Yang, James Chih Hsin

AU - Lu, Shun

AU - Hayashi, Hidetoshi

AU - Felip, Enriqueta

AU - Spira, Alexander I.

AU - Girard, Nicolas

AU - Kim, Yu Jung

AU - Lee, Se Hoon

AU - Ostapenko, Yurii

AU - Danchaivijitr, Pongwut

AU - Liu, Baogang

AU - Alip, Adlinda

AU - Korbenfeld, Ernesto

AU - Dias, Josiane Mourão

AU - Besse, Benjamin

AU - Passaro, Antonio

AU - Lee, Ki Hyeong

AU - Xiong, Hailin

AU - How, Soon Hin

AU - Cheng, Ying

AU - Chang, Gee Chen

AU - Yoshioka, Hiroshige

AU - Thomas, Michael

AU - Nguyen, Danny

AU - Ou, Sai Hong Ignatius

AU - Mukhedkar, Sanjay

AU - Prabhash, Kumar

AU - D’Arcangelo, Manolo

AU - Alatorre-Alexander, Jorge

AU - Limón, Juan Carlos Vázquez

AU - Alves, Sara

AU - Stroyakovskiy, Daniil

AU - Peregudova, Marina

AU - Şendur, Mehmet Ali Na Hit

AU - Yazici, Ozan

AU - Califano, Raffaele

AU - Calderón, Vanesa Gutiérrez

AU - de Marinis, Filippo

AU - Kim, Sang We

AU - Gadgeel, Shirish M.

AU - Owen, Scott

AU - Xie, John

AU - Sun, Tao

AU - Mehta, Jaydeep

AU - Venkatasubramanian, Raja

AU - Ennis, Mariah

AU - Fennema, Elizabeth

AU - Daksh, Mahesh

AU - Roshak, Amy

AU - Man, Julie

PY - 2025/10/30

Y1 - 2025/10/30

N2 - 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 EGFRmutated (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.

AB - 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 EGFRmutated (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.

KW - Hematology/Oncology

KW - Lung Cancer

KW - Pulmonary/Critical Care

KW - Pulmonary/Critical Care General

KW - Treatments in Oncology

UR - https://www.scopus.com/pages/publications/105020620968

U2 - 10.1056/NEJMoa2503001

DO - 10.1056/NEJMoa2503001

M3 - Article

C2 - 40923797

AN - SCOPUS:105020620968

SN - 0028-4793

VL - 393

SP - 1681

EP - 1693

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 17

ER -

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

Abstract

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Keywords

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