Update on Gastroesophageal Adenocarcinoma Targeted Therapies

Gastroesophageal cancer (GEC) remains a major cause of cancer-related mortality worldwide. Although the incidence of distal gastric adenocarcinoma (GC) is declining in the United States, proximal esophagogastric junction adenocarcinoma (EGJ) incidence is rising. GC and EGJ, together, are treated uniformly in the metastatic setting as GEC. Overall survival in the metastatic setting remains poor, with few molecular targeted approaches having been successfully incorporated into routine care to date—only first-line anti-HER2 therapy for ERBB2 amplification and second-line anti-VEGFR2 therapy. This article reviews aberrations in epidermal growth factor receptor, MET, and ERBB2, their therapeutic implications, and future directions in targeting these pathways.

Key points

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Trastuzumab is a treatment standard for HER2 amplified/overexpressed gastroesophageal adenocarcinoma, yet benefit has not been demonstrated in second and later lines of therapy, or beyond progression in first line therapy.
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Anti-epidermal growth factor receptor therapy warrants further investigation for gene amplification/over-expression despite lack of benefit demonstrated in unselected gastroesophageal patients to date.
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Anti-MET therapy has not demonstrated benefit in ‘over-expressing’ gastroesophageal patients in any line of therapy, but evidence supports further investigation in patients with gene amplification/overexpression.