Abstract
Amivantamab, a bispecific antibody targeting EGFR and MET, combined with the third-generation EGFR tyrosine kinase inhibitor (TKI) lazertinib, represents an emerging therapeutic strategy for EGFR-mutant non-small cell lung cancer (NSCLC). Given the high incidence and clinical burden of brain metastases (BM) in this population, characterizing intracranial and systemic efficacy is critical. This meta-analysis evaluates pooled efficacy and safety outcomes of amivantamab plus lazertinib in EGFR-mutant NSCLC patients with BM. A systematic search of PubMed, Embase, Cochrane CENTRAL, and ASCO/SNO/ESMO proceedings was conducted through March 2025 to identify original studies reporting outcomes in EGFR-mutant NSCLC patients with BM treated with this regimen. Key endpoints included systemic progression-free survival (PFS), systemic and intracranial objective response rate (ORR), grade ≥3 adverse events (AEs), treatment discontinuation due to AEs, and venous thromboembolism (VTE) incidence. Binary outcomes were pooled using random-effects models. Median PFS was converted to mean estimates using Wan’s method. Heterogeneity was assessed using I² statistics. Five studies (N=825) were included. All patients had BM; 27.4% received prior EGFR-TKI and 12.0% prior chemotherapy. Median age was 62.9 years (IQR: 55.2–69.4); 35.6% were male. Pooled systemic ORR was 35% (95% CI: 26–44; I²=64.2%, p=0.03), while intracranial ORR was 31% (95% CI: 21–41; I²=58.9%, p=0.04). Grade ≥3 AEs occurred in 71% (95% CI: 67–74; I²=22.7%, p=0.24). Treatment discontinuation due to AEs was 26% (95% CI: 22–31; I²=39.5%, p=0.12). VTE incidence was 15% (95% CI: 7–22; I²=82.6%, p<0.001). Pooled mean systemic PFS was 20.5 months (95% CI: 12.7–28.2; I²=0%, p=0.82), indicating no significant heterogeneity. Amivantamab plus lazertinib demonstrates encouraging intracranial and systemic activity in EGFR-mutant NSCLC with BM. Despite frequent toxicity, these regimens appear clinically active and warrant further investigation in CNS-involved populations.