Systemic therapy for advanced gastroesophageal cancers: progress and pitfalls.

Advanced gastroesophageal cancer in which surgical resection is no longer appropriate is an aggressive malignancy with poor prognosis. This review provides an overview of the key trials that have led to the current standard of care, both highlighting progress with systemic cytotoxic and biological therapies, but also calling attention to pitfalls to assist practitioners in optimizing currently available treatments for their patients. This review surveys recent and ongoing trials and biomarker studies regarding the use of anti-HER2 agents, with increased recognition of molecular intratumoral heterogeneity confounding such targeted therapy strategies. We conclude with an overview of recent major trials incorporating immune checkpoint inhibitors among patients with metastatic and locally advanced gastroesophageal cancer and providing a framework for the discriminate application of these new therapies.