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

// Denis L. Fontes Jardim 1 , Debora de Melo Gagliato 1 , Gerald S. Falchook 1 , Filip Janku 1 , Ralph Zinner 1 , Jennifer J. Wheler 1 , Vivek Subbiah 1 , Sarina A. Piha-Paul 1 , Siqing Fu 1 , Mariela Blum Murphy 2 , Jaffer Ajani 2 , Chad Tang 3 , Kenneth Hess 4 , Stanley R. Hamilton 4 , Sinchita Roy-Chowdhuri 4 , Razelle Kurzrock 5 , Funda Meric-Bernstam 1 , David S. Hong 1 1 Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, USA 2 Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA 3 Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA 3 Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, USA 4 Department of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA 5 Department of Medicine, University of California, San Diego, USA Correspondence: David S. Hong, email: // Keywords : MET mutation, MET amplification, esophageal cancer, gastric cancer, c-MET inhibitor Received : January 28, 2014 Accepted : March 14 , 2014 Published : March 16, 2014 Abstract 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.