Recent Advance and Promising Agents for Gastric Cancer

Abstract

In recent years, various molecular target agents have been investigated for advanced gastric cancer(AGC). Main targets are receptor tyrosine kinase including HER family, angiogenesis system and PI3K-mTOR intracellular signaling system. The anti-HER2 antibody trastuzumab was shown to prolong the overall survival (OS) of patients with HER2-positive AGC, and now become one of the standard treatments. Although lapatinib could not show statistically significant OS benefit for AGC, phase III global studies of other HER2-targeting agents including T-DM1 and pertuzumab are ongoing. Ramcirumab, anti-VEGFR2 monoclonal antibody, showed OS benefit in 2 randomised studies (REGARD and RAINBOW) and waits for its approval. Two negative randomised trials of anti-EGFR antibody (REAL-III and EXPAND) strongly suggest the importance of developing biomarkers to predict the effectiveness of each agent. Phase III or earlier studies which targeting EGFR, cMET-HGF, or FGFR with prescreening by predefined biomarkers are now ongoing. Other promising strategies include target therapies for immune checkpoint (CTLA4, PD-1, and PD-L1) or cancer stemness, which are also evaluated in early clinical trials. These new target therapies may hopefully become the breakthrough for the treatment of AGC.