Amivantamab/Lazertinib Leads to Longer PFS, Duration of Response in EGFR+ NSCLC

The combination of amivantamab-vmjw (Rybrevant) and lazertinib (Leclaza) was more efficacious than osimertinib (Tagrisso) as a frontline treatment for patients with EGFR-mutated non–small cell lung cancer (NSCLC), according to findings from the MARIPOSA trial (NCT04487080) published in The New England Journal of Medicine.¹

Among the total of 1074 patients enrolled, the median progression-free survival (PFS) in the amivantamab/lazertinib arm was 23.7 months compared with 16.6 months in the osimertinib group (HR, 0.70; 95% CI, 0.58-0.8; P <.001). While the overall response rates (ORRs) in both arms were similar, with 86% (95% CI, 83%-89%) in the amivantamab/lazertinib arm and 85% (95% CI, 81%-88%) in the osimertnib arm, the median duration of response was longer in the amivantamab/lazertinib group at 25.8 months (95% CI, 20.1-not estimable [NE]) vs 16.8 months (95% CI, 14.8-18.5). An interim overall survival (OS) analysis showed that amivantamab and lazertinib reduced the risk of death by 20% (HR, 0.80; 95% CI, 0.61-1.05).

Regarding safety, EGFR-related toxic effects were the most common. A total of 10% and 3% of patients in the amivantamab/lazertinib and osimertinib groups, respectively, discontinued treatment due to treated-related adverse effects.

“With the addition of amivantamab, which is a bispecific EGFR/MET antibody, we expected and did have more [adverse] effects. Of course, the [adverse] effects did have to be managed. The typical [adverse] effects are rash, cutaneous reactions, and immune-related adverse events. The most concerning thing over time are not the immune-related reactions, because that's typically just the first dose,” Alexander Spira, MD, PhD, director of the Virginia Cancer Specialists Research Institute and investigator on the MARIPOSA trial, told Targeted Oncology^TM in an interview.

Findings presented at the 2023 European Society for Medical Oncology (ESMO) Annual Congress showed that amivantamab and lazertinib also reduced the risk of extracranial progression or death by 32% vs osimertinib. The median extracranial PFS was 27.5 months (95% CI, 22.1-NE) with the combination vs 18.5 months (95% CI, 16.5-20.3) with osimertinib (HR, 0.68; 95% CI, 0.56-0.83; P <.001). The 12- and 24-month extracranial PFS rates were 77% and 53% with the combination, respectively, vs 67% and 38% with osimertinib.²

Findings from a secondary biomarker analysis were presented at this year’s American Society of Clinical Oncology (ASCO) Annual Meeting.³ Here, the combination continued to show superiority among several patient subgroups.3 Patients with a TP53 co-mutation had a median PFS of 18.2 months with amivantamab plus lazertinib vs 12.9 months with osimertinib (HR, 0.65; P =.003).

Among patients who had detectable circulating tumor DNA (ctDNA) at baseline, the median PFS was 20.3 months vs 14.8 months with the combination vs osimertinib, respectively (HR, 0.68; P =.002). Moreover, the median PFS was improved in patients who had ctDNA clearance at cycle 3, day 1 in the amivantamab/lazertinib arm (24.0 months vs 16.5 months; HR, 0.64; P =.004), as well as in patients who did not have ctDNA clearance (16.5 months vs 9.1 months; HR, 0.48; P =.014).

REFERENCES:

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

2. Cho BC, Felip E, Spira AI, et al. Amivantamab plus lazertinib vs osimertinib as first-line treatment in patients with EGFR-mutated, advanced non-small cell lung cancer (NSCLC): Primary results from MARIPOSA, a phase III, global, randomized, controlled trial. Ann Oncol. 2023;34(suppl 2):S1306. doi:10.1016/j.annonc.2023.10.062

3. Felip E, Cho B, Gutiérrez V, et al. Amivantamab plus lazertinib vs osimertinib in first-line EGFR-mutant advanced non-small cell lung cancer (NSCLC) with biomarkers of high-risk disease: A secondary analysis from the phase 3 MARIPOSA study. J Clin Oncol. 2024:42(suppl 16);8504. doi:10.1200/JCO.2024.42.16_suppl.8504