Overview
- On Tuesday, October 6, 2026, clinicians summarized that amivantamab plus lazertinib (MARIPOSA) and osimertinib plus platinum‑pemetrexed (FLAURA2) have shown overall survival benefit and are both NCCN Category 1 preferred frontline options.
- TP53 co‑mutation is a key biomarker that signals higher risk on TKI alone, and MARIPOSA data showed PFS of 18.2 months versus 12.9 months with osimertinib in TP53‑mutant patients with a hazard ratio of 0.65.
- MARIPOSA required serial brain MRIs and produced robust intracranial efficacy data, and investigators compared intracranial PFS hazard ratios from the two trials (about 0.69 in MARIPOSA with brain metastases versus about 0.56 in FLAURA2) to inform regimen choice.
- The two intensified regimens have different early toxicity patterns: amivantamab‑lazertinib causes mainly dermatologic and infusion‑related events and needs adherence to the COCOON skin‑care and anticoagulation prophylaxis, while osimertinib plus carboplatin‑pemetrexed causes induction hematologic and gastrointestinal toxicities with ongoing pemetrexed effects in maintenance.
- Practices now favor frontline combination therapy for most eligible patients to secure longer disease control, but clinicians stress shared decision‑making because there is no head‑to‑head comparison, and routine NGS and early ctDNA are used to guide sequencing and preserve future treatment options.