Amivantamab/Lazertinib Leads to Longer PFS, Duration of Response in EGFR+ NSCLC
Findings from the MARIPOSA trial showed that amivantamab plus lazertinib were superior to osimertinib for the treatment of EGFR-mutant non–small cell lung cancer.
Lungs anterior view: © 7activestudio - stock.adobe.com
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 OncologyTM 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
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