Dual immune checkpoint blockade in gastroesophageal tumors: never say never

Summary Immunotherapy was proven to be effective as first-line treatment for a subgroup of patients with gastroesophageal tumors and is already established as the standard of care. However, chemotherapy remains the backbone of treatment in both advanced and resectable stages. Dual checkpoint inhibition produces synergistic activation of immune cells and enhanced antitumor activity, and could thus represent an alternative to chemotherapy. So far, there is evidence for the combination strategies of inhibitors of the PD-L1/PD‑1 axis and CTLA4, LAG3 and TIGIT. A combination therapy of nivolumab+ipilimumab has already been approved as first-line treatment for patients with advanced esophageal squamous cell carcinoma. Evaluation of other concepts is ongoing. The aim of this review is to summarize current knowledge about dual inhibition of immune checkpoint inhibitors in the treatment of gastroesophageal carcinoma and to discuss the available evidence from a clinical perspective.