**3.1. Bevacizumab**

Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor (VEGF)-A, which is effective in combination with chemotherapy in several kinds of malignancies including the colon [51], breast [52], and lung [53]. Against the background that the overexpression of VEGF was correlated with tumor aggressiveness and poor prognosis in GC [54, 55], a randomized AVAGAST study was conducted to evaluate the efficacy of adding bevacizumab to capecitabine plus cisplatin in the first-line treatment of advanced GC [56]. The results did not meet the primary outcome; however, adding bevacizumab to chemotherapy resulted in a significant prolongation of mPFS and a significant increase in RR. In the subgroup analysis of AVAGAST study, geographical differences in efficacy were suggested, it being effective in Pan-America whereas not so in Asia and Europe. Subsequently, an AVATAR trial in which the trial design is similar with that of AVAGAST has been conducted for 202 Chinese patients with the results recently published [57]. Again, neither mOS nor mPFS were improved by the addition of bevacizumab to chemotherapy. Based on the negative results of the two RCTs, research should be continued to seek the biomarker predictive for bevacizumab efficacy in order to determine the bevacizumab rational position in the treatment of advanced GC [58]. Candidates for potential predictive biomarkers include plasma VEGF-A level and tissue neuropilin-1 expression [58]. However, other cancers had potential other predictive markers for bevacizumab efficacy, being VEGF-A and VEGFR-2 in breast cancer [59] or VEGFR-1 singlenucleotide polymorphism in pancreatic and renal cell cancer [60].
