Format

Send to

Choose Destination
Clin Genitourin Cancer. 2015 Feb;13(1):e19-26. doi: 10.1016/j.clgc.2014.06.017. Epub 2014 Jul 3.

MET abnormalities in patients with genitourinary malignancies and outcomes with c-MET inhibitors.

Author information

1
Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas M.D. Anderson Cancer Center, Houston, TX. Electronic address: denis.ljardim@hsl.org.br.
2
Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas M.D. Anderson Cancer Center, Houston, TX.
3
Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
4
Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
5
Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
6
Department of Pathology and Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
7
Department of Medicine, University of California, San Diego, La Jolla, CA.

Abstract

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.

KEYWORDS:

Bladder cancer; MET amplification; MET mutation; Prostate cancer; Renal cell cancer

PMID:
25087088
PMCID:
PMC5144738
DOI:
10.1016/j.clgc.2014.06.017
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center