MET abnormalities in patients with genitourinary malignancies and outcomes with c-MET inhibitors. Clin Genitourin Cancer 2015 Feb;13(1):e19-26
Date
08/05/2014Pubmed ID
25087088Pubmed Central ID
PMC5144738DOI
10.1016/j.clgc.2014.06.017Scopus ID
2-s2.0-84920623892 (requires institutional sign-in at Scopus site) 17 CitationsAbstract
BACKGROUND: The purpose of this study was to determine the prevalence of MET amplification and mutation among GU malignancies and its association with clinical factors and responses to c-MET inhibitors.
PATIENTS AND METHODS: Patients with GU malignancies referred to our Phase I Clinical Trials Program were evaluated for MET mutation and amplification and outcomes using protocols with c-MET inhibitors.
RESULTS: MET amplification was found in 7 of 97 (7.2%) patients (4/27 renal [all clear cell], 1/18 urothelial, and 2/12 adrenocortical carcinoma), with MET mutation/variant in 3 of 54 (5.6%) (2/20 renal cell carcinoma [RCC] [1 clear cell and 1 papillary] and 1/16 prostate cancer). No demographic characteristics were associated with specific MET abnormalities, but patients who tested positive for mutation or amplification had more metastatic sites (median, 4 vs. 3 for wild type MET). Median overall survival after phase I consultation was 6.1 and 11.5 months for patients with and without a MET alteration, respectively (hazard ratio, 2.8; 95% confidence interval, 1.1 to 6.9; P = .034). Twenty-nine (25%) patients were treated according to a c-MET inhibitor protocol. Six (21%) had a partial response (prostate and RCC) and 10 (34%) had stable disease as best response. Median time to tumor progression was 2.3 months (range, 0.4-19.7) for all treated patients with no responses in patients with a MET abnormality or single-agent c-MET inhibitor treatment.
CONCLUSION: MET genetic abnormalities occur in diverse GU malignancies and are associated with a worse prognosis in a phase I setting. Efficacy of c-MET inhibitors was more pronounced in patients without MET abnormalities and when combined with other targets/drugs.
Author List
Jardim DL, de Melo Gagliato D, Falchook G, Zinner R, Wheler JJ, Janku F, Subbiah V, Piha-Paul SA, Fu S, Tannir N, Corn P, Tang C, Hess K, Roy-Chowdhuri S, Kurzrock R, Meric-Bernstam F, Hong DSAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Aged
Antineoplastic Agents
Clinical Trials, Phase I as Topic
Female
Gene Amplification
Humans
Male
Middle Aged
Mutation
Protein Kinase Inhibitors
Proto-Oncogene Proteins c-met
Retrospective Studies
Survival Analysis
Treatment Outcome
Urogenital Neoplasms
Young Adult
