The Role of Angiogenesis Targeted Therapies in Metastatic Advanced Gastric Cancer: A Narrative Review

Since bevacizumab was first approved by the U.S. Food and Drug Administration as an anti-angiogenic therapy in 2004, angiogenesis-targeted therapy has been developed for various types of solid tumors. To date, ramucirumab and apatinib are clinically available as treatments for metastatic advanced gastric cancer (AGC). Ramucirumab demonstrated prolonged survival as second-line therapy of metastatic AGC in the RAINBOW and REGARD trials. However, neither ramucirumab extended survival in treatment-naïve patients with AGC in the RAINFALL or RAINSTORM trials nor bevacizumab in the AVAGAST and AVATAR trials. Apatinib demonstrated superior efficacy over the best supportive care in a Chinese phase III trial but not in an international phase III (ANGEL) trial. Currently, combination therapy of ramucirumab with irinotecan or FTD/TPI is being evaluated in the third-line setting, assessing the efficacy of continuous angiogenesis inhibition from second- to third-line therapy. Recently, the role of angiogenesis inhibition via immunomodulators is attractive to clinicians. Emerging results of several early-phase clinical trials indicated the promising antitumor activity of angiogenesis inhibition in combination with immune therapy. This review offers an overview of the history of clinical trials focused on anti-angiogenic for patients with AGC and presents future perspectives in this area.