Lazertinib Versus Osimertinib in Previously Untreated EGFR-mutant Advanced NSCLC: A Randomized, Double-blind, Exploratory Analysis From MARIPOSA

INTRODUCTION: Lazertinib is a CNS-penetrant, third-generation epidermal growth factor (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) and overall survival versus osimertinib in participants with treatment-naïve EGFR-mutant advanced non-small cell lung cancer. A lazertinib monotherapy arm was included to assess the contribution of components in the combination. This is the first randomized, double-blind comparison of 2 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 (HR, 0.98; 95% CI, 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 (HR, 1.00; 95% CI, 0.73-1.38) at the interim analysis. Adverse events for both arms were mostly grade 1-2 and frequently related to EGFR inhibition. Lazertinib was associated with lower rates of QT interval prolongation versus osimertinib. CONCLUSIONS: Lazertinib showed comparable efficacy and safety to osimertinib, including in predefined subgroups.

• 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.
• Mourão Dias, J.
• Lee, K. H.
• Xiong, H.
• How, S. H.
• Cheng, Y.
• Chang, G. C.
• Yang, J. C.
• 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.