title: MET aberrations and c-MET inhibitors in patients with gastric and esophageal cancers in a phase I unit.
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.
authors.affiliation: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: Denis L Fontes
authors.initials: DL
authors.lastname: Jardim
authors.forename: Debora
authors.initials: D
authors.lastname: de Melo Gagliato
authors.forename: Gerald S
authors.initials: GS
authors.lastname: Falchook
authors.forename: Filip
authors.initials: F
authors.lastname: Janku
authors.forename: Ralph
authors.initials: R
authors.lastname: Zinner
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Wheler
authors.forename: Vivek
authors.initials: V
authors.lastname: Subbiah
authors.forename: Sarina A
authors.initials: SA
authors.lastname: Piha-Paul
authors.forename: Siqing
authors.initials: S
authors.lastname: Fu
authors.forename: Mariela Blum
authors.initials: MB
authors.lastname: Murphy
authors.forename: Jaffer
authors.initials: J
authors.lastname: Ajani
authors.forename: Chad
authors.initials: C
authors.lastname: Tang
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hess
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Hamilton
authors.forename: Sinchita
authors.initials: S
authors.lastname: Roy-Chowdhuri
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
authors.forename: Funda
authors.initials: F
authors.lastname: Meric-Bernstam
authors.forename: David S
authors.initials: DS
authors.lastname: Hong
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000235:genetics*; D004943:Esophagogastric Junction; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000235:genetics*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics*; D015996:Survival Rate
chemical_list: D004273:DNA, Neoplasm; D047428:Protein Kinase Inhibitors; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
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