Role of Immunotherapy in Gastroesophageal Cancers—Advances, Challenges and Future Strategies

SIMPLE SUMMARY: Gastric and esophageal cancers represent a global health concern with considerable associated morbidity and mortality. The management of these malignancies was historically limited to chemotherapy, radiotherapy and surgery. More recently, immunotherapies, which can harness the immune system to treat cancer, have become an established treatment option in many cancer types. This article presents the existing evidence for the use of immunotherapies in gastric and esophageal cancers that are localized to one area or that have spread to other areas. It considers challenges in terms of the use of these agents and also discusses immune-based treatments that are currently under investigation in this area which may potentially change treatment practices in the future. ABSTRACT: Background: Gastroesophageal cancers (GECs) carry considerable morbidity and mortality, and demonstrate geographical histological variances in addition to molecular heterogeneity. Consequently, the immunogenicity of the different subtypes, which can predict the likelihood of immunotherapy response, can vary. Immune checkpoint inhibitor (ICI) therapy has transformed the treatment of many cancer types over the past decade but has been slower to gain a foothold in the treatment paradigm of GECs. Methods: This article reviews the existing evidence and use approvals for immunotherapies and immune-based treatments in GECs, in the neoadjuvant, adjuvant and metastatic disease settings. The challenges of and limitations to ICI application in current clinical practice are examined. Ongoing clinical trials and future directions of research are also considered. Conclusion: ICI therapy has become an established treatment option within GECs, both perioperatively and in advanced disease. However, nuances in terms of its use are not yet fully understood. Ongoing research proposes to broaden the application of immunotherapies in GECs with the potential to continue to improve outcomes.