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

Abstract

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.