Predictive Markers and Targeted Therapies in Gastroesophageal Cancer (GEC)

Abstract

For more than 15 years, several combination therapies have been used in the treatment of advanced gastroesophageal cancer (GEC) raising the median survival rate from about 3 to 4 months (best supportive care) to about 8-11 months. The most important achievement was the introduction of trastuzumab in combination with 5-FU/cisplatin or capecitabine/cisplatin as first-line therapy in HER2-positive advanced GEC. Recent ASCO/CAP guidelines recommend immunohistochemical assessment as the first diagnostic step with ISH confirmation only in IHC2+ equivocal cases. Another agent (ramucirumab) has been approved for second-line therapy directed against VEGFR2 but without any biomarker. A number of other drugs targeting transmembranous growth factor receptors and downstream signaling pathways have been evaluated but so far without final results or approvals. Most promising data have recently been shown for checkpoint inhibitors using anti PD1/PD-L1 therapies where a demonstration of mismatch repair deficiency (MMRd) or immunohistochemical demonstration of PD-L1 expression seems to be of predictive value.