MET aberrations and c-MET inhibitors in patients with gastric and esophageal cancers in a phase I unit
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Denis L. Fontes Jardim1, Debora de Melo Gagliato1, Gerald S. Falchook1, Filip Janku1, Ralph Zinner1, Jennifer J. Wheler1, Vivek Subbiah1, Sarina A. Piha-Paul1, Siqing Fu1, Mariela Blum Murphy2, Jaffer Ajani2, Chad Tang3, Kenneth Hess4, Stanley R. Hamilton4, Sinchita Roy-Chowdhuri4, Razelle Kurzrock5, Funda Meric-Bernstam1, David S. Hong1
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
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
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.
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