Clinical significance of combination of anti-angiogenesis, immune checkpoint inhibitors and chemotherapy in the neoadjuvant treatment of locally advanced gastric cancer

Abstract

The combination of anti-angiogenesis, immune checkpoint inhibitors(ICIs) and chemotherapy(target-immune-chemo) has achieved initial results in the comprehensive treatment of gastric cancer. Experimental studies have shown that among various determinants of tumor immunotherapy, tumor microenvironment (TME) plays a crucial role in affecting ICIs efficacy. The biological mechanism leading to immunosuppressive TME is multi-factorial and very complex, but one of clear and important mechanisms is the influence of abnormal neoangiogenesis in tumors. The use of low-dose targeted tumor angiogenesis drugs (such as anti-VEGF /VEGFR monoclonal antibody, etc.) is expected to make tumor vessels normalization and reverse immunosuppressive TME to immunesupportive TME, so as to play synergistic, complementary, anti-tumor effects with ICIs and chemotherapy drugs. Perioperative treatment of locally advanced gastric cancer (LAGC) has become an indispensable and important strategy in surgical comprehensive treatment of gastric cancer. In recent years, a therapeutic combination regimen of anti-angiogenesis, ICIs and chemotherapy (target-immune-chemo) has been clinically applied in the perioperative treatment of LAGC, and the preliminary efficacy [pathologic complete response(pCR), major pathological response(MPR), tumor regression grade(TRG) and treatment-related adverse events(TRAEs), etc.] has shown encouraging results. This article reviewed the relevant clinical research results and made a summary and analysis.

Keywords

• |locally advanced gastric cancer|neoadjuvant therapy|anti-angiogenesis|immune checkpoint inhibitors|chemotherapy