Effectiveness and safety of the amivantamab to lazertinib versus lazertinib alone in EGFR mutant metastatic non-small-cell lung cancer: Systematic review and meta-analysis.

e20677 Background: Epidermal Growth Factor Receptor (EGFR) mutant metastatic non-small-cell lung cancer (NSCLC) is a major global health problem. Targeted therapies, including tyrosine kinase inhibitors (TKIs) like lazertinib, have shown promising results. This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of amivantamab in combination with lazertinib compared to lazertinib alone in the treatment of EGFR mutant metastatic NSCLC. Methods: A systematic review was done, including six eligible studies published up to December 2024. Databases such as PubMed, Embase, and Cochrane Library were searched. Outcomes assessed included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety profiles. The risk of bias was assessed using the Cochrane Risk of Bias tool. Meta-analysis was performed using a random-effects model. Results: The addition of amivantamab to lazertinib was associated with substantially better PFS (hazard ratio [HR]: 0.67, 95% CI: 0.54–0.80, p < 0.001) and OS (HR: 0.72, 95% CI: 0.60–0.85, p < 0.001) compared with lazertinib monotherapy. ORR was also significantly greater in the combination group (65.3% vs. 48.9%, p < 0.01). While AEs were more common with combination therapy, most were controllable, with grade 3–4 AEs mainly composed of diarrhea, rash, and hepatotoxicity. Conclusions: The combination of amivantamab and lazertinib provides greater efficacy than monotherapy with lazertinib for EGFR mutant metastatic NSCLC, and the safety profile is acceptable. These findings support the integration of combination therapy into clinical practice, although further large-scale randomized trials are warranted.