Combined Inhibition of EGFR and VEGF Pathways in Patients with EGFR-Mutated Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Abstract

Dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways could potentiate improved outcomes in patients with metastatic EGFR-mutated non-small cell lung cancer (NSCLC). The purpose of this systematic review and meta-analysis was to compare the efficacy of an EGFR tyrosine kinase inhibitor (TKI) plus a VEGF inhibitor with EGFR TKI alone for the treatment of EGFR-mutated NSCLC. We systematically searched for randomized controlled trials (RCT) that involved patients with EGFR-mutated metastatic NSCLC treated with combination therapy versus EGFR TKI alone. In a pooled analysis of 5 studies, treatment with the combination therapy was associated with statistically significant improvements in progression-free survival (hazard ratio [HR] 0.63, 95% CI [0.54, 0.75]) when compared with control. However, pooled data from 4 studies revealed no statistically significant differences between the 2 groups for overall survival (HR 1.00, 95% CI [0.68, 1.52]) and the objective response rate (relative risk [RR] 1.05, 95% CI [0.97, 1.14]). In patients with metastatic EGFR-mutated NSCLC, treatment with EGFR TKI plus VEGF inhibition provided significant improvements in progression-free survival, but not in overall survival or objective response rate, when compared with treatment with EGFR TKI alone.