Immunotherapy in Gastric Cancer

Abstract

Immune checkpoint inhibition is a new standard of targeted therapy in the treatment of advanced or metastatic gastric cancer (GC) and is represented in various combinations with and without chemotherapy in every therapy line within clinical trials. In advanced adenocarcinoma of GC, gastroesophageal junction cancer (GEJC) and esophageal cancer (EC), the combination of nivolumab and chemotherapy in first-line therapy improves overall survival (OS) in PD-L1 (programmed cell death protein 1)-positive patients with approval in Europe (PD-L1 CPS (combined positivity score) ≥ 5), USA and Taiwan (CHECKMATE-649) and pembrolizumab plus chemotherapy for GEJC and EC in Europe (CPS ≥ 10) and the USA (KEYNOTE-590). Furthermore, pembrolizumab plus trastuzumab and chemotherapy show clear benefits in OS and are approved as first-line treatment of Her2 (human epidermal growth factor receptor-2)-positive tumors in the USA (KEYNOTE-811). Nivolumab demonstrates superior OS regardless of PD-L1 expression in third-line therapy with approval in Japan (ATTRACTION-02) and pembrolizumab prolonged the duration of response in PD-L1 positive patients with approval in the USA in PD-L1 CPS ≥ 1 patients (KEYNOTE-059). This review reflects the rationale and current results of phase II and III clinical trials investigating various immune checkpoint inhibitors targeting PD-L1/1 and CTLA (anticytotoxic T-lymphocyte-associated antigen)-4 in combination with and without chemotherapy and Her2-targeted therapy in GC.

Atlas of PD-L1 for Pathologists: Indications, Scores, Diagnostic Platforms and Reporting Systems

“…In this context, it had to be clarified that a real predictive role for this biomarker has been acknowledged for tumors of the esophagus, esophago–gastric junction and stomach [ 30 ]. Conversely, for intestinal cancers and for tumors of the pancreatobiliary system, PD-L1 has no recognized role in predicting the response to immunotherapy [ 30 , 31 , 32 , 33 , 34 ].…”

Recent Progress and Future Perspectives of Immunotherapy in Advanced Gastric Cancer

“…For patients whose immune systems fail to detect and response to cancer cells, adoptive cell therapy has been proved as effective strategies to treat advanced gastric cancer (36). Adoptive cell therapy utilizes various immune cells including tumour infiltrating lymphocytes (TILs), lymphokine-activated killer cells and cytokine-induced killer (CIK) cells to induce effective immunity to clear cancer cells (2,37). CIK cells are derived from peripheral blood lymphocytes in the presence of CD3 monoclonal antibodies, IL-2 and IFN-g (38).…”

“…Gastric cancer is the third leading cause of cancer-related death (1). Due to the delay in diagnosis and lack of effective therapies, patients with advanced gastric cancer suffer from poor prognosis and a short lifespan of approximately one year (2). The commonly used therapies of advanced gastric cancer are radiotherapy, chemotherapy and targeted therapy.…”

Expression profiles of m6A RNA methylation regulators, PD-L1 and immune infiltrates in gastric cancer

“…It achieves a therapeutic effect by inducing, enhancing or regulating immune response. Immunotherapy for gastric cancer currently consists primarily of immune checkpoint inhibitor therapy ( 7 , 8 ).…”