Abstract B063: Efficacy of amivantamab in patients with EGFR-mutated non-small cell lung cancer (NSCLC): A meta-analysis of phase 3 randomized controlled trials

Abstract Background: Amivantamab is a bispecific antibody targeting epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET), approved for EGFR-mutant non-small cell lung cancer (NSCLC) in May 2021. While initial approval focused on exon 20 insertions, recent phase III trials have evaluated its efficacy in classical EGFR mutations. This meta-analysis was conducted to quantify the impact of amivantamab on progression-free survival (PFS). Methods: A systematic search of MEDLINE and EMBASE was conducted through inception to July 10, 2025, to identify phase III randomized controlled trials (RCTs) evaluating amivantamab in patients with EGFR-mutant non-small cell lung cancer (NSCLC). The primary endpoint was progression-free survival (PFS). Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using the generic inverse variance method. Heterogeneity across studies was assessed using Cochran’s Q test, and a random-effects model was applied to account for inter-study variability. Results: A total of 1,823 patients from three phase III RCTs (MARIPOSA, MARIPOSA-2, PAPILLON) were included. Amivantamab significantly improved PFS versus control (HR 0.50; 95% CI: 0.38–0.66; p<0.00001). Subgroup analyses showed consistent benefit: patients >65 years (HR 0.60; CI: 0.36–0.97; p=0.04) and <65 years (HR 0.46; CI: 0.39–0.53; p<0.00001); females (HR 0.47; CI: 0.33–0.67; p<0.0001) and males (HR 0.59; CI: 0.49–0.71; p<0.00001); ECOG 0 (HR 0.48; CI: 0.33–0.71; p=0.0002) and ECOG 1 (HR 0.53; CI: 0.43–0.65; p<0.00001); with brain metastases (HR 0.56; CI: 0.45–0.71; p<0.00001) and without (HR 0.47; CI: 0.34–0.65; p<0.00001); smokers (HR 0.53; CI: 0.39–0.72; p<0.0001) and never-smokers (HR 0.51; CI: 0.39–0.65; p<0.00001). Benefit was also observed for EGFR exon 19 deletions (HR 0.57; CI: 0.46–0.71; p<0.00001) and L858R mutations (HR 0.49; CI: 0.28–0.85; p=0.01), demonstrating broad efficacy across clinically relevant subgroups. Conclusion: This meta-analysis demonstrates amivantamab provides a clinically meaningful improvement in progression-free survival among patients with EGFR-mutant non-small cell lung cancer. The benefit was consistent across key subgroups, including different ages, sexes, performance statuses, smoking histories, brain metastasis status, and EGFR mutation subtypes. These findings support the incorporation of amivantamab into the standard treatment paradigm for EGFR-mutant NSCLC, particularly in the frontline setting. Citation Format: Daniel Thomas. Jones, Riccesha Hattin, Jason Ta, Abbas Hussain, Ramaditya Srinivasmurthy, Rishi Kumar. Nanda, Clinton Lam, Kyaw Zin. Thein. Efficacy of amivantamab in patients with EGFR-mutated non-small cell lung cancer (NSCLC): A meta-analysis of phase 3 randomized controlled trials [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr B063.