Current and Future Aspects of Immunotherapy for Esophageal and Gastric Malignancies

Esophagogastric (EG) cancer has a poor prognosis despite the use of standard therapies, such as chemotherapy and biologic agents. Recently, immune checkpoint inhibitors (ICIs) have been introduced as treatments for EG cancer; nivolumab and pembrolizumab have been approved in the United States and Europe to treat advanced EG cancer. Other ICIs, such as avelumab, durvalumab, ipilimumab, and tremelimumab, have been evaluated in several trials, although their roles are still not established in clinical practice. In addition, preclinical evidence suggests that combining an ICI with a tumor-targeting antibody can result in greater antitumor effects in metastatic EG cancer. There are not yet validated predictive biomarkers to identify which patients will respond best to ICI treatment. PD-L1 expression may predict intensity of response, although PD-L1-negative patients can still respond to ICIs. Despite differences in PD-L1 expression between Asian and non-Asian populations, no geographic differences in rates of treatment-related or immune-mediated/infusion-related adverse events have been reported. Also, several trials are currently evaluating combinations of ICIs, standard chemotherapy, and biologic agents as well as novel biomarkers to improve treatments and outcomes. Our review will address the current use of and evidence for ICIs for advanced EG cancer treatment and future trends in this area for clinical practice.