TY - JOUR
T1 - MET abnormalities in patients with genitourinary malignancies and outcomes with c-MET inhibitors
AU - Jardim, Denis L.F.
AU - De Melo Gagliato, Débora
AU - Falchook, Gerald
AU - Zinner, Ralph G
AU - Wheler, Jennifer Jane
AU - Janku, Filip
AU - Subbiah, Vivek
AU - Piha-Paul, Sarina A.
AU - Fu, Siqing
AU - Tannir, Nizar
AU - Corn, Paul
AU - Tang, Chad
AU - Hess, Kenneth R
AU - Roy-Chowdhuri, Sinchita
AU - Kurzrock, Razelle
AU - Meric-Bernstam, Funda
AU - Hong, David S.
N1 - Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/2/1
Y1 - 2015/2/1
N2 - 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.
AB - 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.
KW - Bladder cancer
KW - MET amplification
KW - MET mutation
KW - Prostate cancer
KW - Renal cell cancer
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U2 - 10.1016/j.clgc.2014.06.017
DO - 10.1016/j.clgc.2014.06.017
M3 - Article
C2 - 25087088
AN - SCOPUS:84920623892
SN - 1558-7673
VL - 13
SP - e19-e26
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
IS - 1
ER -