Gastroesophageal Cancers and Immunotherapy Updates

Although relatively uncommon in the United States, cancers of the stomach and esophagus constitute a significant global health problem with approximately 1.6 million new cases, and 1.25 million deaths, per year worldwide. There is overlap in the underlying biology, prognosis, and treatment of these diseases, however, they should be considered distinct entities. For example, squamous cell cancers of the upper esophagus share more molecular features with cancers of the head and neck than adenocarcinomas of the stomach or lower esophagus. Molecular heterogeneity also exists among esophageal and gastric adenocarcinomas, and microsatellite instability and programmed cell death ligand 1 (PD-L1) have emerged as meaningful biomarkers for response to immune checkpoint inhibitors. Despite these advancements, outcomes are still poor and there has been a concerted effort to develop new treatment strategies for patients with esophagogastric cancers. Early clinical research established the activity of nivolumab and pembrolizumab as monotherapy in later lines of therapy for advanced disease. Recent randomized trials with these agents have drastically changed the treatment landscape, demonstrating improved survival in the adjuvant setting (CheckMate 577), in combination with other immune-checkpoint inhibitors (CheckMate 649), and in combination with chemotherapy (CheckMate 648, KEYNOTE 590, KEYNOTE 811). After this activity, clinicians will be able to explain the underlying biological rationale for using immunotherapy in the management of gastroesophageal cancers and apply evidence-based strategies for incorporating such agents into the treatment plan for patients.