A narrative review of the evolving landscape of the management of metastatic gastric cancer: the role of targeted therapies

Background and Objective: Gastric cancer is the fifth most common cancer worldwide and the fourth leading cause of cancer-related death. Unfortunately, patients often present with advanced disease at diagnosis, which is directly related to its high mortality. Numerous trials, as early as the 1980’s, have shown that cytotoxic chemotherapy improves survival. This review will focus on targeted therapies and immunotherapies which have emerged as treatment options for metastatic gastric cancer, often used in conjunction with cytotoxic chemotherapy. Here we will review the relevant clinical trials of targeted therapies and immunotherapies in the treatment of metastatic gastric cancer. Methods: We performed an extensive review of articles in the PubMed database pertaining to targeted therapies and immunotherapies in the treatment of metastatic gastric cancer. Additionally, updated guidelines from the National Comprehensive Cancer Network (NCCN) and European Society for Medical Oncology (ESMO) were reviewed. Key Content and Findings: Cytotoxic chemotherapy remains the backbone of treatment of metastatic gastric cancer, but the development of targeted therapies and immunotherapy have revolutionized its treatment with improved survival and outcomes. Therapies have been developed which target human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor receptor-2 (VEGFR-2), and tyrosine kinase pathways. Novel targeted therapies are currently being investigated with promising results thus far. Immunotherapy, specifically immune checkpoint inhibitors (ICIs), has proven to be a significant advancement in the treatment of gastric cancer. Conclusions: Targeted therapies and immunotherapies have improved survival and outcomes in metastatic gastric cancer, however more research is needed to make even greater strides.