As reported in The New England Journal of Medicine by Yang et al, the final overall survival analysis in the phase III MARIPOSA trial has shown significant benefit with amivantamab plus lazertinib vs osimertinib in patients with previously untreated EGFR-mutated advanced non–small cell lung cancer (NSCLC).
The primary analysis from the trial showed significantly improved progression-free survival with amivantamab plus lazertinib vs osimertinib.
Study Details
In the international open-label trial, 1,074 patients were randomly assigned 2:2:1 between November 2020 and May 2022 to receive amivantamab plus lazertinib (n = 429), osimertinib (n = 429), or lazertinib (n = 216). A total of 250 patients in the amivantamab plus lazertinib group and 251 in the osimertinib group were Asian. Overall survival with amivantamab plus lazertinib vs osimertinib was a key secondary endpoint.
Key Findings
In the protocol-specified final analysis, the median follow-up was 37.8 months (range = 0.0–48.1 months).
At time of analysis, death had occurred in 173 patients in the amivantamab plus lazertinib group vs 217 in the osimertinib group. Median overall survival was not reached vs 36.7 months (hazard ratio = 0.75, 95% confidence interval [CI] = 0.61–0.92, P =.005); rates at 3 years were 60% vs 51%.
In total, 175 patients (41%) in the amivantamab plus lazertinib group and 258 (60%) in the osimertinib group had disease progression and discontinued assigned treatment; among these, 129 (74%) in the amivantamab plus lazertinib group and 195 (76%) in the osimertinib group received subsequent anticancer therapy. At the clinical cutoff date, 38% vs 28% of patients continued to receive assigned treatment.
Overall, grade ≥ 3 adverse events occurred in 80% of the amivantamab plus lazertinib group vs 52% of the osimertinib group. The most common in the amivantamab plus lazertinib group were rash (17%), paronychia (12%), pulmonary embolism (9%), and acneiform dermatitis (9%); the most common in the osimertinib group were dyspnea (4%) and pulmonary embolism (3%). No new safety signals were observed with additional follow-up.
The investigators concluded: “Amivantamab-lazertinib led to significantly longer overall survival among participants with previously untreated EGFR-mutated advanced NSCLC than osimertinib but was associated with an increased risk of adverse events of grade 3 or higher.”
Byoung Chul Cho, MD, PhD, of Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea, is the corresponding author for The New England Journal of Medicine article.
Disclosure: The study was funded by Janssen Research and Development. For full disclosures of all study authors, visit nejm.org.
