Identification of a small and lethal subgroup of esophagogastric adenocarcinoma with evidence of responsiveness to crizotinib by MET amplification.

4130 Background: Amplification of the MET proto-oncogene in gastroesophageal cancer (GEC) may constitute a molecular marker for targeted therapy. We examined a GEC cohort with follow-up and report the response in two patients with MET-amplified tumors to the small molecule inhibitor crizotinib. Methods: From 2007-2009 patients with GEC were genetically screened as a consecutive series of 489 tumors. MET, EGFR and HER2 amplification status was assessed using fluorescent in situ hybridization with a strict definition of amplification. The clinical response of two additional patients enrolled in an expanded phase I cohort study (ClinicalTrials.gov NCT00585195) is included. Results: 10 patients out of 489 screened (2%) harbored MET amplification, 23 (4.7%) harbored EGFR amplification, 44 (8.9%) harbored HER2 amplification, and 411 (84%) were wild-type for all three genes (triple negative, TN). MET-amplified tumors were typically high-grade adenocarcinomas that presented in advanced stages. EGFR-amplified tumo...