Clinical efficacy of immune checkpoint inhibitors in the treatment of unresectable advanced or recurrent gastric cancer: an evidence-based review of therapies

Abstract

Kazuhiro Togasaki, Yasutaka Sukawa, Takanori Kanai, Hiromasa Takaishi Department of Internal Medicine, Division of Gastroenterology and Hepatology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan Abstract: Standard treatment options for patients with advanced gastric cancer (GC) offer limited efficacy and are associated with some toxicity, which necessitates the development of more effective therapies for improving the treatment outcomes for this disease. Immunotherapy involving immune checkpoint inhibitors (ICIs) which inhibit the programmed death 1 (PD-1)/programmed death ligand 1 interaction has emerged as a new treatment option. Nivolumab, a human IgG4 monoclonal antibody inhibitor of PD-1, has demonstrated promising clinical activity and induced durable responses in patients with advanced GC. Nivolumab has recently been approved for treating patients with pretreated advanced GC in Japan. In the present review, we summarized current evidence of the clinical efficacy of ICIs in a variety of solid tumors and reported our experience in patients with GC who were treated with nivolumab and the interesting features that were observed in these cases. Certain ICI-specific clinical features such as pseudo- and hyper-progression of tumor and hyper-response to subsequent chemotherapy have been reported in several cancer types. Lastly, we discussed the present scenario regarding research on biomarkers for assessing the clinical benefits of ICI therapies. Keywords: nivolumab, pembrolizumab, avelumab, pseudoprogression, hyperprogression, hypersensitivity, microbiome

Keywords

• Gastric cancer
• nivolumab
• pseudo-progression
• hyper-progression
• hyper-response
• biomarker