Cautious Optimism—The Current Role of Immunotherapy in Gastrointestinal Cancers

Abstract

Immunotherapy has been described as the “fourth pillar” of oncology treatment, in conjunction with surgery, chemotherapy, and radiotherapy. However, the role of immunotherapy in gastrointestinal tumours is still evolving. Data for checkpoint inhibition in esophagogastric, hepatocellular, colorectal, and anal squamous cell carcinomas are expanding. In phase iii trials in the second-line setting, PD-1 inhibitors have demonstrated positive results for the subset of esophageal cancers that are positive for PD-L1 at a combined positive score of 10 or more. Based on results of phase ii trials, PD-1 inhibitors were approved in North America for use in PD-L1–positive chemorefractory gastric cancers, in hepatocellular carcinoma after sorafenib exposure, and in treatment-refractory deficient mismatch repair (dmmr) or high microsatellite instability (msi-h) tumours, regardless of tissue site. Combination use of PD-1 and ctla-4 inhibitors has been approved by the U.S. Food and Drug Administration for chemorefractory dmmr or msi-h colorectal cancer. Responses to checkpoint inhibition are durable, particularly in the dmmr or msi-h colorectal cancer cohort. As trials of combination immunotherapy, immunotherapy in combination with other systemic therapies, and immunotherapy in combination with other treatment modalities move forward in multiple tumour sites, cautious optimism is called for. The treatment landscape is continually changing, and expanded indications are likely to be just around the corner.