Advancing immunotherapy in gastroesophageal cancer through rational combinations and biomarkers.

The impact of checkpoint inhibitors on gastroesophageal cancer treatment has been tremendous in the last 2 years. KEYNOTE-590, CHECKMATE 649 and CheckMate 648 are landmark trials that have introduced immunotherapy to the field as first-line therapy, leading to a paradigm change for advanced esophageal and gastric cancer. Chemotherapy in combination with immunotherapy is now the standard of care for first-line treatment of locally advanced or metastatic adenocarcinoma of the esophagus, esophagogastric junction and stomach. Several new targets and treatments are available for gastroesophageal cancer that are based on the characterization of cancer cells and the tumor microenvironment. Biomarker-based therapy selection is critical to optimize outcomes and minimize toxicities, as well as give insight into the optimal timing and sequence of a patient's treatment course.