Comparison Between EGFR-TKI Efficacy in Early-Stage Non-small Cell Lung Cancer and Advanced Non-small Cell Lung Cancer: A Systematic Review and Meta-analysis.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the standard of care for advanced non-small cell lung cancer (NSCLC). However, their comparative efficacy and safety profile in early-stage versus advanced-stage disease remains systematically unexplored. We performed a systematic review and meta-analysis of PubMed, Embase, Cochrane Library, and Web of Science through January 4, 2025. Included studies reported objective response rate (ORR), disease control rate (DCR), or treatment-related adverse events (TRAEs) for EGFR-TKI monotherapy. Pooled estimates were synthesized using a generalized linear mixed model (GLMM). Forty-two studies comprising 46 treatment groups and 3713 patients (343 early-stage; 3370 advanced-stage) were included. The pooled ORR was significantly higher in advanced-stage NSCLC (0.59, 95% CI 0.51-0.67) than in early-stage disease (0.36, 95% CI 0.15-0.63). In contrast, early-stage disease achieved a higher DCR (0.95 vs. 0.89). Early-stage patients experienced a significantly lower incidence of Grade ≥3 TRAEs compared to those with advanced disease (8.0% vs. 21%). EGFR-TKIs provide superior tumor shrinkage (ORR) in advanced NSCLC, the reasons remain uncertain, whereas early-stage disease achieves better disease stability (DCR) with significantly enhanced tolerability. These findings suggest that stage-specific strategies-potentially combining TKIs with other modalities in early stages-are necessary to optimize clinical outcomes.