The New England Journal of MedicineAmivantamab plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC

Combination Therapy in EGFR-Mutated NSCLC: Potential to Extend Progression-Free Survival and Response Duration

A recent phase 3 randomized trial evaluated the efficacy of amivantamab plus lazertinib compared to osimertinib in patients with previously untreated, advanced non–small-cell lung cancer (NSCLC) harboring EGFR mutations. The study aimed to determine if the combination therapy could offer superior progression-free survival and response duration over the current standard treatment with osimertinib.

Study Design:

• Participants: 1074 patients with EGFR-mutated (exon 19 deletion or L858R) locally advanced or metastatic NSCLC.
• Randomization: Patients were assigned in a 2:2:1 ratio to receive either amivantamab–lazertinib (429 patients), osimertinib (429 patients), or lazertinib (216 patients).
• Primary Endpoint: Progression-free survival, assessed by blinded independent central review.

Key Findings:

• Progression-Free Survival: Median of 23.7 months in the amivantamab–lazertinib group versus 16.6 months in the osimertinib group (hazard ratio for disease progression or death, 0.70; P<0.001).
• Objective Response Rate: 86% in the amivantamab–lazertinib group versus 85% in the osimertinib group.
• Response Duration: Median response duration of 25.8 months with amivantamab–lazertinib versus 16.8 months with osimertinib.
• Overall Survival: Interim analysis showed a hazard ratio for death of 0.80 (95% CI, 0.61 to 1.05) favoring amivantamab–lazertinib.
• Adverse Events: Predominantly EGFR-related toxic effects; treatment discontinuation due to adverse events was 10% for amivantamab–lazertinib and 3% for osimertinib.

HCN Medical Memo
The phase 3 study demonstrates that amivantamab plus lazertinib offers significant improvements in progression-free survival and response duration over osimertinib in EGFR-mutated advanced NSCLC. This combination therapy presents a viable first-line treatment option, potentially altering the clinical approach to managing these patients.

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