MET aberrations and c-MET inhibitors in patients with gastric and esophageal cancers in a phase I unit

We sought to investigate the demographics and tumor-associated features in patients with gastroesophageal (GE) malignancies referred to our Phase I Program who had formalin-fixed, paraffin-embedded tissue from archival or new biopsies tested for MET mutation and/or amplification. MET amplification was found in 5 of 76 (6.6%) patients (3/34 [8.8%] esophageal, 2/26 [7.7%] gastric and none in 22 gastroesophageal junction cancers). The only MET mutation detected in 3 of 41 (7.3%) patients was N375S. No demographic and histologic characteristics were associated with specific MET abnormalities. Median overall survival was 3 and 5 months for patients with and without a MET alteration, respectively (hazard ratio [HR] = 2.1; 95% CI, 0.8 to 5.5; P=.14). Sixteen of 81 (20%) patients were enrolled in a c-MET inhibitor trial. Best responses were stable disease in 3 patients (19%), including a patient with esophageal adenocarcinoma that remained on the trial for 9.9 months (wild-type for MET abnormality). All tumors with MET abnormality (n=3) progressed on a c-MET inhibitor in fewer than 2 months. In conclusion, MET abnormalities can be found in a small group of patients with GE adenocarcinoma and further studies are necessary to better characterize the prognostic and predictive impact of MET alterations.