The role of anti-VEGF agents in the treatment of advanced gastric cancer: a meta-analysis of randomized controlled trials.

Inhibition of vascular epithelial growth factor (VEGF) signaling pathways has proven to be an effective strategy for the treatment of several common solid tumors, but its role in the management of advanced gastric cancer (AGC) is yet to be defined. We performed a meta-analysis of randomized controlled trials (RCTs) to assess the efficacy and safety of anti-VEGF agents in the treatment of AGC. Several databases were searched, including PubMed, Embase, and Cochrane databases. The endpoints were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade 3 or 4 adverse events (AEs). The pooled hazard ratio (HR) or relative risk (RR) and 95 % confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. Seven RCTs which involved 2,340 patients were ultimately identified. The pooled analysis demonstrated that anti-VEGF therapy significantly improved OS (HR 0.74, 95 % CI 0.61-0.91, p = 0.003), PFS (HR 0.59, 95 % CI 0.44-0.78, p < 0.001), and ORR (RR 1.43, 95 % CI 1.14-1.79, p = 0.002) when compared to non-anti-VEGF therapy. Sensitivity analysis further confirmed this association. Additionally, more incidences of grade 3 or 4 thrombocytopenia, diarrhea, and hypertension were observed in anti-VEGF therapy. The anti-VEGF therapy offers a significant survival benefit in patients with AGC, especially for those previously treated patients, when compared to non-anti-VEGF therapy. With the present available data from randomized clinical trials, we could not clearly set the role of specific anti-VEGF agents in the treatment of AGC. Further studies are recommended to identify patients who could derive greater benefits from specific anti-VEGF agents.