Emerging Insights From MARIPOSA: OS Updates From Amivantamab/Lazertinib in Advanced NSCLC

EP: 1.Clinical Case: EGFR-Mutant (Ex19del) Advanced NSCLC

EP: 2.The Treatment Landscape For Advanced EGFR-Mutant NSCLC

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EP: 3.Emerging Insights From MARIPOSA: OS Updates From Amivantamab/Lazertinib in Advanced NSCLC

EP: 4.Navigating CNS Disease in EGFR-Mutant NSCLC

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The MARIPOSA study represents a landmark phase 3 randomized trial that has fundamentally changed the treatment landscape for EGFR-mutant advanced non–small cell lung cancer (NSCLC). This pivotal study randomly assigned 1074 patients in a 2:1 fashion comparing amivantamab plus lazertinib combination vs osimertinib monotherapy, with lazertinib serving as a nonregistrational arm to assess its contribution to the overall treatment regimen. The study successfully met its primary end point, demonstrating significant improvement in progression-free survival, with a median PFS of 23.7 months vs 16.6 months for osimertinib (HR, 0.7).

The most significant development from MARIPOSA was the recent reporting of mature overall survival data, showing a remarkable 25% improvement in overall survival favoring the amivantamab plus lazertinib combination. The median overall survival has not yet been reached for the combination arm compared with approximately 36 months with osimertinib monotherapy. This overall survival benefit represents unprecedented outcomes in the EGFR-mutant NSCLC space and provides compelling evidence for the superiority of the combination approach in appropriate patients.

When comparing findings from the MARIPOSA study with those from the FLAURA2 study, both demonstrate positive primary end points with comparable progression-free survival benefits. However, MARIPOSA’s advantage lies in its mature overall survival data whereas FLAURA2’s overall survival data remain immature at approximately 41% maturation, with a similar HR of 0.75. This maturity difference provides clinicians with more definitive evidence to support treatment decisions, though both regimens remain viable options in clinical practice. The MARIPOSA results have elevated the amivantamab plus lazertinib combination as a preferred frontline option for many practitioners, particularly for patients who can safely receive the combination therapy.