Amivantamab–Lazertinib Extends Progression-Free Survival in Untreated EGFR-Mutated NSCLC

Progression-free survival was significantly longer with amivantamab–lazertinib compared with osimertinib as first-line treatment of untreated EGFR (epidermal growth factor receptor)-mutated advanced non-small-cell lung cancer (NSCLC), according to a study published online ahead of print in the New England Journal of Medicine.

The phase 3 clinical trial randomly assigned 1074 patients with untreated EGFR-mutated (exon 19 deletion or L858R) locally advanced or metastatic NSCLC to receive open-label amivantamab–lazertinib (429 patients), blinded osimertinib (429 patients), or blinded lazertinib (216 patients). The study’s primary end point was progression-free survival in the amivantamab-lazertinib group compared with the osimertinib group. The amivantamab–lazertinib group had a median profession-free survival of 23.7 months compared with 16.6 months for the osimertinib group, according to the study. The hazard ratio for disease progression or death was 0.70 with amivantamab–lazertinib compared with osimertinib.

Rates of observed objective response were 86% with amivantamab–lazertinib and 85% with osimertinib. Observed responses were confirmed in 336 patients in the amivantamab–lazertinib group and in 314 patients in the osimertinib group. Median response durations for patients with a confirmed response were 25.8 months with amivantamab–lazertinib and 16.8 months with osimertinib, the study found.

A planned interim overall survival analysis found a 0.80 hazard ratio for death with amivantamab–lazertinib compared with osimertinib, but the result was not significant.

“The number of deaths in our trial was inadequate to provide robust conclusions about overall survival …” researchers wrote. “Longer follow-up is needed to detect whether there is an overall survival benefit with amivantamab–lazertinib.”

Rates of discontinuation of all agents because of treatment-related adverse events were 10% with amivantamab–lazertinib and 3% with osimertinib. Rates of adverse events leading to death were 8% with amivantamab-lazertinib and 7% with osimertinib, investigators reported.

Reference

Cho BC, Lu S, Felip E, et al. Amivantamab plus lazertinib in previously untreated EGFR-mutated advanced NSCLC. N Engl J Med. Published online June 26, 2024. doi:10.1056/NEJMoa2403614