As reported in The New England Journal of Medicine by Byoung Chul Cho, MD, PhD, and colleagues, the phase III MARIPOSA trial has shown improved progression-free survival with amivantamab-vmjw plus lazertinib vs osimertinib in previously untreated patients with EGFR-mutated advanced non–small cell lung cancer (NSCLC).

Byoung Chul Cho, MD, PhD

Study Details

In the international trial, 1,074 patients were randomly assigned 2:2:1 between November 2020 and May 2022 to receive open-label amivantamab/lazertinib (n = 429), blinded osimertinib (n = 429), or blinded lazertinib (n = 216). Amivantamab was given at 1,050 mg once weekly for the first 4 weeks followed by 1,050 mg every 2 weeks. Osimertinib at 80 mg and lazertinib at 240 mg were given once daily.

The primary endpoint of the trial was progression-free survival in the amivantamab/lazertinib group vs the osimertinib group on blinded independent central review. In the amivantamab/lazertinib group, 58% of patients were Asian and 38% were White; in the osimertinib group, 59% of patients were Asian and 38% were White.

Progression-Free Survival

Median progression-free survival was 23.7 months (95% confidence interval [CI] = 19.1–27.7 months) in the amivantamab/lazertinib group vs 16.6 months (95% CI = 14.8–18.5 months) in the osimertinib group (hazard ratio [HR] = 0.70, 95% CI = 0.58–0.85, P < .001). Rates at 18 and 24 months were 60% vs 48% and 48% vs 34%, respectively. Median progression-free survival in the lazertinib group was 18.5 months (95% CI = 14.8–20.1 months).

Median extracranial progression-free survival was 27.5 months (95% CI = 22.1 months to not evaluable) in the amivantamab/lazertinib group vs 18.4 months (95% CI = 16.5–20.2 months) in the osimertinib group.

Objective response was observed in 86% of patients in the amivantamab/lazertinib group and 85% of those in the osimertinib group; median response durations were 25.8 months (95% CI = 20.1 months to not evaluable) vs 16.8 months (95% CI = 14.8–18.5 months).

In an interim analysis of overall survival in the amivantamab/lazertinib vs osimertinib group, the hazard ratio was 0.80 (95% CI = 0.61–1.05). Rates at 18 and 24 months were 82% vs 79% and 74% vs 69%, respectively.

Adverse Events

Grade ≥ 3 adverse events occurred in 75% of patients in the amivantamab/lazertinib group vs 43% of those in the osimertinib group. The most common in the amivantamab/lazertinib group were rash (in 15% of patients), paronychia (in 11%), pulmonary embolism (in 8%), and acneiform dermatitis (in 8%); the most common in the osimertinib group included dyspnea (in 4%), increased alanine aminotransferase (in 2%), and pulmonary embolism (in 2%). Venous thromboembolic adverse events of any grade occurred in 37% vs 9% of patients. Infusion-related reactions of any grade occurred in 63% of those in the amivantamab/lazertinib group. Adverse events led to discontinuation of treatment in 35% vs 14% (treatment-related in 10% vs 3%). Adverse events led to death in 8% vs 7% of patients.

The investigators concluded, “Amivantamab/lazertinib showed superior efficacy to osimertinib as first-line treatment in EGFR-mutated advanced NSCLC.”

Dr. Cho, of Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, 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 the study authors, visit nejm.org.