Research Papers:
MET aberrations and c-MET inhibitors in patients with gastric and esophageal cancers in a phase I unit
Metrics: PDF 2776 views | HTML 3334 views | ?
Abstract
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
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 1828