**3.2. Ramucirumab**

Ramucirumab is a fully humanized monoclonal antibody that blocks the binding of VEGF-A, C, and D to the extracellular domain of VEGF receptor-2 (VEGFR-2); thus, ramucirumab inhibits the ligand activation of a downstream signal transduction of VEGF-R [61]. The REGARD trial is the first RCT demonstrating survival benefits for second-line ramucirumab when compared with the best supportive care [62]. Subsequently, the RAINBOW trial was conducted to evaluate the second-line efficacy of weekly paclitaxel with or without ramucirumab [63]. The subgroup analysis demonstrated that ramucirumab was not effective in Asian patients when compared with those from Europe and the USA; however, this geographical difference was ascribed partly to the high proportion of patients receiving postdiscontinuation therapy—at least for Japanese patients [64]. Currently, ramucirumab has been evaluated as a first-line setting in combination with fluoropyrimidines and cisplatin (RAINFALL trial) [65] or in combination with FOLFOX [66].
