Lazertinib Versus Osimertinib in Previously Untreated EGFR-Mutant Advanced NSCLC: A Randomized, Double-Blind, Exploratory Analysis From MARIPOSA
Issued Date
2025-01-01
Resource Type
ISSN
15560864
eISSN
15561380
Scopus ID
2-s2.0-105012856780
Pubmed ID
40617394
Journal Title
Journal of Thoracic Oncology
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Thoracic Oncology (2025)
Suggested Citation
Lee S.H., Lu S., Hayashi H., Felip E., Spira A.I., Girard N., Kim Y.J., Ostapenko Y., Danchaivijitr P., Liu B., Alip A., Korbenfeld E., Dias J.M., Lee K.H., Xiong H., How S.H., Cheng Y., Chang G.C., Chih-Hsin Yang J., Besse B., Thomas M., Shah S., Baig M., Curtin J.C., Zhang J., Xie J., Sun T., Sethi S., Wang M., Fennema E., Daksh M., Ennis M., Bauml J.M., Cho B.C. Lazertinib Versus Osimertinib in Previously Untreated EGFR-Mutant Advanced NSCLC: A Randomized, Double-Blind, Exploratory Analysis From MARIPOSA. Journal of Thoracic Oncology (2025). doi:10.1016/j.jtho.2025.06.030 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/111683
Title
Lazertinib Versus Osimertinib in Previously Untreated EGFR-Mutant Advanced NSCLC: A Randomized, Double-Blind, Exploratory Analysis From MARIPOSA
Author(s)
Lee S.H.
Lu S.
Hayashi H.
Felip E.
Spira A.I.
Girard N.
Kim Y.J.
Ostapenko Y.
Danchaivijitr P.
Liu B.
Alip A.
Korbenfeld E.
Dias J.M.
Lee K.H.
Xiong H.
How S.H.
Cheng Y.
Chang G.C.
Chih-Hsin Yang J.
Besse B.
Thomas M.
Shah S.
Baig M.
Curtin J.C.
Zhang J.
Xie J.
Sun T.
Sethi S.
Wang M.
Fennema E.
Daksh M.
Ennis M.
Bauml J.M.
Cho B.C.
Lu S.
Hayashi H.
Felip E.
Spira A.I.
Girard N.
Kim Y.J.
Ostapenko Y.
Danchaivijitr P.
Liu B.
Alip A.
Korbenfeld E.
Dias J.M.
Lee K.H.
Xiong H.
How S.H.
Cheng Y.
Chang G.C.
Chih-Hsin Yang J.
Besse B.
Thomas M.
Shah S.
Baig M.
Curtin J.C.
Zhang J.
Xie J.
Sun T.
Sethi S.
Wang M.
Fennema E.
Daksh M.
Ennis M.
Bauml J.M.
Cho B.C.
Author's Affiliation
Universitat Autònoma de Barcelona
Universiti Malaya
German Cancer Research Center
National Taiwan University Hospital
Samsung Medical Center, Sungkyunkwan university
Université de Versailles Saint-Quentin-en-Yvelines
Institut de Cancerologie Gustave Roussy
Harbin Medical University
International Islamic University Malaysia
Seoul National University Bundang Hospital
Siriraj Hospital
Kindai University School of Medicine
Chung Shan Medical University Hospital
Johnson & Johnson
Shanghai Chest Hospital
Johnson & Johnson Pharmaceutical Research & Development, Raritan
Chungbuk National University Hospital
Yonsei Cancer Hospital
Hospital de Câncer de Barretos
Hospital Britanico de Buenos Aires
National Cancer Institute of Ukraine
Jilin Cancer Hospital
Virginia Cancer Specialists
Huizhou Municipal Central Hospital of Guangdong Province
Universiti Malaya
German Cancer Research Center
National Taiwan University Hospital
Samsung Medical Center, Sungkyunkwan university
Université de Versailles Saint-Quentin-en-Yvelines
Institut de Cancerologie Gustave Roussy
Harbin Medical University
International Islamic University Malaysia
Seoul National University Bundang Hospital
Siriraj Hospital
Kindai University School of Medicine
Chung Shan Medical University Hospital
Johnson & Johnson
Shanghai Chest Hospital
Johnson & Johnson Pharmaceutical Research & Development, Raritan
Chungbuk National University Hospital
Yonsei Cancer Hospital
Hospital de Câncer de Barretos
Hospital Britanico de Buenos Aires
National Cancer Institute of Ukraine
Jilin Cancer Hospital
Virginia Cancer Specialists
Huizhou Municipal Central Hospital of Guangdong Province
Corresponding Author(s)
Other Contributor(s)
Abstract
Introduction: Lazertinib is a central nervous system–penetrant, third-generation EGFR tyrosine kinase inhibitor (TKI) that was selected for combination with amivantamab due to its relatively low rates of wild-type EGFR toxicities. In the phase 3 MARIPOSA study, amivantamab plus lazertinib (amivantamab-lazertinib) significantly improved progression-free survival (PFS; p < 0.001) versus osimertinib in participants with treatment-naive EGFR-mutant advanced NSCLC. A lazertinib monotherapy arm was included to assess the contribution of components in the combination. This is the first randomized, double-blind comparison of two third-generation EGFR TKIs, lazertinib and osimertinib. Methods: In MARIPOSA, 1074 participants were randomized 2:2:1 to receive amivantamab-lazertinib (n = 429), osimertinib monotherapy (n = 429), or lazertinib monotherapy (n = 216). This exploratory analysis compared the efficacy and safety of lazertinib and osimertinib. Results: At a median follow-up of 22.0 months, median PFS was 18.5 months for lazertinib versus 16.6 months for osimertinib (hazard ratio = 0.98, 95% confidence interval: 0.79–1.22; p = 0.86). PFS results were comparable between arms among predefined subgroups. Among participants with measurable disease at baseline, objective response rate was 83% for lazertinib versus 85% for osimertinib, with a median duration of response among confirmed responders of 16.6 months versus 16.8 months, respectively. Median overall survival was not reached for both arms (hazard ratio = 1.00, 95% confidence interval: 0.73–1.38) at the interim analysis. Adverse events for both arms were mostly grades 1 to 2 and frequently related to EGFR inhibition. Lazertinib was associated with lower rates of QT interval prolongation versus osimertinib. Conclusions: Lazertinib demonstrated comparable efficacy and safety to osimertinib, including in predefined subgroups.