Immunotherapy for advanced gastric and esophageal cancer: preclinical rationale and ongoing clinical investigations

Gastric and esophageal cancers represent a major global cancer burden and novel approaches are needed. Despite recent improvements in outcomes with trastuzumab and ramucirumab the prognosis for advanced disease remains poor, with a median overall survival of 1 year. Comprehensive genomic characterization has defined molecular subgroups and potentially actionable genomic alterations, but the majority of patients do not yet benefit from molecularly directed therapies. Breakthroughs in immune checkpoint blockade have provided new therapeutic avenues in melanoma, and continue to expand into other tumor types, with ongoing investigations in gastrointestinal (GI) malignancies. The frequency of programmed death ligand 1 (PD-L1) overexpression, a putative response biomarker, approaches forty percent in gastric cancers. Translational studies and molecular classification suggest gastric and esophageal cancers are candidate malignancies for immune checkpoint inhibition trials and early clinical data is promising. Here we review the mechanisms, preclinical, and early clinical data supporting the role for immune checkpoint blockade in gastric and esophageal cancer.