Amivantamab plus lazertinib versus osimertinib as first-line treatment in EGFR-mutated advanced non-small cell lung cancer

Introduction: The incidence of epidermal growth factor receptor (EGFR) mutations is higher among Asian patients with advanced non-small cell lung cancer than the general advanced non-small cell lung cancer population. We evaluated the efficacy and safety of amivantamab in combination with lazertinib versus osimertinib in Asian participants from the phase 3 MARIPOSA study who had treatment-naïve advanced non-small cell lung cancer with common EGFR mutations. Methods: Participants were randomized 2:2:1 to receive amivantamab-lazertinib, osimertinib alone, or lazertinib alone. The primary endpoint was progression-free survival based on blinded independent central review per RECIST v1.1. Secondary endpoints included overall survival, objective response rate, duration of response, and safety. Exploratory endpoints included extracranial progression-free survival and post-progression outcomes. Results: Of 1074 randomized participants, 629 were Asian, with 250 and 251 randomized to the amivantamab-lazertinib and osimertinib arms, respectively. Among Asian participants, at a median follow-up of 22.5 months, amivantamab-lazertinib showed a 35 % reduction in the risk of disease progression or death versus osimertinib (hazard ratio, 0.65; P < 0.001). Consistent with the overall population, median progression-free survival was 27.5 and 18.3 months in the amivantamab-lazertinib and osimertinib arms, respectively. The objective response rate was 88 % for amivantamab-lazertinib versus 85 % for osimertinib. The median duration of response among confirmed responders improved by 8.6 months for amivantamab-lazertinib versus osimertinib. Favorable trends were also seen for overall survival, extracranial progression-free survival, and post-progression outcomes for amivantamab-lazertinib over osimertinib. Adverse events in Asian participants were similar to those in the overall population. Conclusions: Amivantamab-lazertinib demonstrated superior progression-free survival versus osimertinib in Asian participants, with a tolerable safety profile. These results were consistent with those in the overall population.