Background: To investigate the effect of combined epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) receptor (VEGFR) pathway inhibitors on progression-free survival (PFS) and overall survival (OS) in patients with non-small-cell lung cancer (NSCLC).
Materials and methods: We included 15 randomized clinical trials that had compared the combination of EGFR tyrosine kinase inhibitors and anti-VEGF/VEGFR therapy with different control groups. Pooled estimates of treatment efficacy were calculated, and subgroup analyses were conducted according to treatment line and EGFR status.
Results: Ten of 15 trials involving 3317 NSCLC patients were included. For all settings, the combined regimen demonstrated no PFS (hazard ratio [HR], 0.82; P = .10) or OS (HR, 0.97; P = .54) benefit compared with the control groups. In the first-line setting, combined therapy showed similar PFS (HR, 1.01; P = .99) but poor OS (HR, 1.36; P = .03) compared with the control groups. In the second-line or subsequent settings, combined therapy resulted in significantly longer PFS (HR, 0.75; P < .01) but similar OS (HR, 0.93; P = .16) compared with the control groups. A subgroup analysis stratified by EGFR status suggested that combined treatment substantially improved PFS (HR, 0.57; P = .04) and OS (HR, 0.45; P < .01) in patients with EGFR mutations rather than EGFR wild type.
Conclusion: EGFR-tyrosine kinase inhibitors plus anti-VEGF/VEGFR therapy significantly prolonged PFS in the second-line treatment of NSCLC patients. An EGFR mutation is a promising indication for this combination treatment. More data are required to confirm this strategy in first-line therapy.
Keywords: EGFR mutation; NSCLC; Survival; Tyrosine kinase inhibitor; VEGF.
Copyright © 2016 Elsevier Inc. All rights reserved.