Current and Future Therapies for Advanced Gastric Cancer

The treatment of patients with advanced gastric cancer remains a challenging area of oncology. Extensive trials of differing chemotherapy regimens have yielded no international consensus on the optimal combination, and overall survival with chemotherapy alone remains poor. Recently an improved understanding of the molecular drivers of the disease has opened up promising new avenues of treatment through the use of biological targeted agents. The anti-HER2 monoclonal antibody trastuzumab was the first targeted agent to significantly prolong survival in the first-line treatment of a molecularly-selected subgroup of patients. More recently the anti vascular endothelial growth factor receptor 2 monoclonal antibody ramucirumab has demonstrated a modest survival benefit in previously treated patients as both a monotherapy and in combination with chemotherapy. Immunotherapy and the use of checkpoint inhibitors are a further exciting area of development with promising preliminary results for the activity of the anti-Programmed Death 1 Receptor antibody pembrolizumab and ongoing trials of a number of immune-modulating agents. Continuing research to identify novel targets and therapies aims to make further incremental gains in survival. In this review we outline the evidence base supporting current chemotherapy regimens and describe the latest advances in the development and use of molecularly targeted and immune-modulating agents. (C) 2015 Published by Elsevier Inc. All rights reserved.