MARIPOSA final OS results establish amivantamab + lazertinib superiority over osimertinib in first-line EGFRm NSCLC

At ELCC 2025 (March 26–29), the Phase III MARIPOSA trial (NCT04487080) reported that first-line amivantamab-vmjw (Rybrevant) plus lazertinib significantly improved overall survival compared to osimertinib (Tagrisso) in patients with EGFR exon 19 deletion or L858R mutations. The combination achieved a hazard ratio (HR) of 0.75 for OS, with a projected survival advantage exceeding 12 months. Median PFS was also superior (23.7 vs 16.6 months). The regimen provided intracranial progression-free survival (PFS) benefit, with manageable toxicity largely consisting of low-grade EGFR/MET-related events such as rash and paronychia. This outcome reinforces the dual targeting approach in EGFRm NSCLC and affirms prior PFS benefits observed in earlier analyses. Regulatory approvals for the combination followed in both the U.S. and EU in early 2025, making it the first combination regimen approved in the front-line setting for common EGFR mutations. The MARIPOSA results were contextualized with earlier FLAURA2 data (Tagrisso + chemo), with experts noting superior tolerability and duration of benefit with the RYB+LAZ combination. Commercial uptake is expected to be rapid, particularly in younger and high-risk populations.‍

Citation: https://dailyreporter.esmo.org/european-lung-cancer-congress-2025/highlights-from-elcc-2025/overall-survival-benefit-achieved-with-amivantamab-plus-lazertinib-in-advanced-egfr-mutated-nsclc

Implication: Positions RYB+LAZ as new standard-of-care in first-line EGFRm NSCLC, displacing Tagrisso monotherapy.

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