Immune Checkpoint Inhibitors in the Treatment of Gastroesophageal Cancer

Immune checkpoint blockade has revolutionised the treatment of multiple cancers including melanoma, non-small cell lung cancer, urothelial and renal cell cancers. For patients with chemorefractory gastroesophageal cancer, treatment with anti-PD-1 therapy results in modest benefits in overall survival; nivolumab and pembrolizumab have been licenced in Japan and the USA, respectively, for this indication. However, initial enthusiasm has been tempered by the results of several large negative trials; immune checkpoint blockade is not superior to chemotherapy in the second-line setting or beyond in unselected or low PD-L1-expressing patients. Microsatellite instability is uncommon in patients with metastatic gastric cancer; however, it is associated with response rates of more than 50% and long-term survival benefit. Combining anti-PD-1 with cytotoxic chemotherapy and targeted therapies also shows promise to extend the benefit of immune checkpoint blockade to a larger proportion of gastroesophageal cancer patients. In this review we discuss recently reported and ongoing clinical research in immunotherapy for gastroesophageal cancer, and consider molecular biology associated with sensitivity and resistance to immune checkpoint blockade in gastroesophageal cancer patients.