Systemic therapy and targeted agents in advanced esophageal cancer

This chapter summarizes recent progress in the treatment of patients with advanced adenocarcinoma of the esophageal and gastroesophageal junction, with a focus on the clinical development of systemic targeted agents. To date, monoclonal antibodies targeting the human epidermal growth factor receptor (HER) 2 (trastuzumab) and tumor-related angiogenesis (ramucirumab) have been shown to improve overall survival in Phase 3 trials of esophagogastric adenocarcinoma, whereas a lack of meaningful efficacy has been demonstrated by epidermal growth factor receptor (EGFR)-targeted monoclonal antibodies (cetuximab, panitumumab) and small molecule inhibitors (gefitinib). Benefit from the dual EGFR/HER2-targeted tyrosine kinase inhibitor, lapatinib, appears to be limited, although responsive subpopulations may be identified. Success in further development of anti-cancer therapies in advanced disease will likely rely on focusing patient enrollment on those with actionable molecular targets.