Faculty Collaboration Database

MET aberrations and c-MET inhibitors in patients with gastric and esophageal cancers in a phase I unit. Oncotarget 2014 Apr 15;5(7):1837-45

Date

04/20/2014

Pubmed ID

24742823

Pubmed Central ID

PMC4039117

DOI

10.18632/oncotarget.1828

Scopus ID

2-s2.0-84899030304 (requires institutional sign-in at Scopus site)   27 Citations

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.

Author List

Jardim DL, de Melo Gagliato D, Falchook GS, Janku F, Zinner R, Wheler JJ, Subbiah V, Piha-Paul SA, Fu S, Murphy MB, Ajani J, Tang C, Hess K, Hamilton SR, Roy-Chowdhuri S, Kurzrock R, Meric-Bernstam F, Hong DS

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Adult
Aged
Aged, 80 and over
DNA Mutational Analysis
DNA, Neoplasm
Disease-Free Survival
Esophageal Neoplasms
Esophagogastric Junction
Female
Gene Amplification
Humans
Male
Middle Aged
Mutation
Protein Kinase Inhibitors
Proto-Oncogene Proteins c-met
Stomach Neoplasms
Survival Rate