Lazertinib versus osimertinib in previously untreated EGFR-mutant advanced NSCLC: a randomized, double-blind, exploratory analysis from MARIPOSA
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 (amivanta...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
November 2025
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| In: |
Journal of thoracic oncology
Year: 2025, Volume: 20, Issue: 11, Pages: 1655-1668 |
| ISSN: | 1556-1380 |
| DOI: | 10.1016/j.jtho.2025.06.030 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.jtho.2025.06.030 Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S1556086425008214 
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| Author Notes: | Se-Hoon Lee, MD, PhD, Shun Lu, MD, PhD, Hidetoshi Hayashi, MD, PhD, Enriqueta Felip, MD, PhD, Alexander I. Spira, MD, PhD, Nicolas Girard, MD, PhD, Yu Jung Kim, MD, PhD, Yurii Ostapenko, MD, PhD, Pongwut Danchaivijitr, MD, Baogang Liu, MD, Adlinda Alip, MD, Ernesto Korbenfeld, MD, Josiane Mourão Dias, MD, Ki Hyeong Lee, MD, Hailin Xiong, MD, Soon Hin How, MD, Ying Cheng, MD, Gee-Chen Chang, MD, PhD, James Chih-Hsin Yang, MD, PhD, Benjamin Besse, MD, PhD, Michael Thomas, MD, Sujay Shah, MD, Mahadi Baig, MD, MHCM, Joshua C. Curtin, PhD, Jiarui Zhang, PhD, John Xie, PhD, Tao Sun, PhD, Seema Sethi, DO, Miao Wang, MD, PhD, Elizabeth Fennema, MA, Mahesh Daksh, PhD, Mariah Ennis, MS, Joshua M. Bauml, MD, Byoung Chul Cho, MD, PhD |
| Summary: | 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. |
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| Item Description: | Online verfügbar 3 July 2025, Version des Artikels 5 November 2025 Gesehen am 12.03.2026 |
| Physical Description: | Online Resource |
| ISSN: | 1556-1380 |
| DOI: | 10.1016/j.jtho.2025.06.030 |