Clinical Context & MARIPOSA Efficacy in 1L EGFRm NSCLC

Dr. Sarah Goldberg from Yale University School of Medicine and Dr. Misako Nagasaka from UCI Health open a discussion on subcutaneous amivantamab every 4 weeks plus lazertinib as a first-line treatment for EGFR-mutated advanced non–small cell lung cancer (NSCLC). The focus centers on the efficacy data that established amivantamab plus lazertinib as a category 1 preferred regimen and the rationale for moving toward a subcutaneous, every-4-week formulation. Dr. Goldberg reviews the phase 3 MARIPOSA trial, which randomized more than 1,000 previously untreated patients with common EGFR mutations 2:2:1 to intravenous amivantamab plus lazertinib, osimertinib, or lazertinib alone. Median progression-free survival was 23.7 months with amivantamab plus lazertinib versus 16.6 months with osimertinib (HR, 0.70; P<.001), and the 3-year overall survival rate was 60% versus 51%, respectively (HR, 0.75; P=.005). Median overall survival was not reached with amivantamab plus lazertinib versus 36.7 months with osimertinib. Although overall response rates were similar at 86% versus 85%, median duration of response was longer with the combination at 25.8 versus 16.8 months. Dr. Goldberg notes that protocol-mandated serial brain MRIs in MARIPOSA enabled reliable CNS assessment, with intracranial progression-free survival favoring amivantamab plus lazertinib (HR, 0.79) and a 36-month landmark intracranial PFS rate of 36% versus 18%. She adds that the high rate of infusion-related reactions seen with intravenous amivantamab created a clear need for the subcutaneous, extended-interval dosing examined in the PALOMA program.

In the next episode, "Selecting Among Preferred 1L Regimens," Drs. Goldberg and Nagasaka discuss patient-level factors that drive the choice between amivantamab + lazertinib, osimertinib, and osimertinib + chemotherapy.