TY - JOUR
T1 - MET nucleotide variations and amplification in advanced ovarian cancer
T2 - Characteristics and outcomes with c-Met inhibitors
AU - Tang, Chad
AU - Jardim, Denis L.Fontes
AU - Falchook, Gerald S.
AU - Hess, Kenneth R
AU - Fu, Siqing
AU - Wheler, Jennifer Jane
AU - Zinner, Ralph G
AU - Naing, Aung
AU - Tsimberidou, Apostolia M.
AU - Galgiato, Debora De Melo
AU - Westin, Shannon N.
AU - Meric-Bernstam, Funda
AU - Kurzrock, Razelle
AU - Hong, David S.
PY - 2014
Y1 - 2014
N2 - Purpose: MET alterations including amplifications and nucleotide variations have been associated with resistance to therapy and aggressive clinical behavior. Experimental Design: The medical records of patients presenting to the University of Texas MD Anderson Cancer Center Phase I Clinic with relapsed or metastatic ovarian cancers and known MET nucleotide variation or amplification status were reviewed retrospectively (n=178). Categorical and continuous clinical and molecular characteristics were compared using Fisher's exact and Wilcoxon rank-sum tests, respectively. Univariate and multivariate survival were assessed via Kaplan- Meier and Cox regression analysis, respectively. Results: MET amplification occurred in 4 (3.5%) of 113 patients, whereas nonsynonomous nucleotide variations were present in 9 (7.4%) of 122 patients. No patients exhibited concomitant amplification and variation. MET variations were observed only in white women with high-grade ovarian tumors, whereas amplifications were observed in both black and white women with high-grade serous ovarian primary tumors. No patients (n=4) exhibiting a MET alteration achieved an objective response when treated on a c-Met inhibitor phase I trial. In addition, ovarian cancer patients treated with a c-Met inhibitor with multikinase activity trended towards a longer time-to-failure compared with those treated with a c-Met-specific inhibitor (median: 1.5 vs. 4.5 months, p=0.07). Conclusions: MET alterations occur in a minority of patients with ovarian cancer. c-Met inhibitors with multikinase activity may exhibit greater activity in ovarian cancer than c-Met specific drugs. These findings warrant further investigation.
AB - Purpose: MET alterations including amplifications and nucleotide variations have been associated with resistance to therapy and aggressive clinical behavior. Experimental Design: The medical records of patients presenting to the University of Texas MD Anderson Cancer Center Phase I Clinic with relapsed or metastatic ovarian cancers and known MET nucleotide variation or amplification status were reviewed retrospectively (n=178). Categorical and continuous clinical and molecular characteristics were compared using Fisher's exact and Wilcoxon rank-sum tests, respectively. Univariate and multivariate survival were assessed via Kaplan- Meier and Cox regression analysis, respectively. Results: MET amplification occurred in 4 (3.5%) of 113 patients, whereas nonsynonomous nucleotide variations were present in 9 (7.4%) of 122 patients. No patients exhibited concomitant amplification and variation. MET variations were observed only in white women with high-grade ovarian tumors, whereas amplifications were observed in both black and white women with high-grade serous ovarian primary tumors. No patients (n=4) exhibiting a MET alteration achieved an objective response when treated on a c-Met inhibitor phase I trial. In addition, ovarian cancer patients treated with a c-Met inhibitor with multikinase activity trended towards a longer time-to-failure compared with those treated with a c-Met-specific inhibitor (median: 1.5 vs. 4.5 months, p=0.07). Conclusions: MET alterations occur in a minority of patients with ovarian cancer. c-Met inhibitors with multikinase activity may exhibit greater activity in ovarian cancer than c-Met specific drugs. These findings warrant further investigation.
KW - C-Met inhibitor
KW - MET amplification
KW - MET nucleotide variations
KW - Ovarian cancer
UR - http://www.scopus.com/inward/record.url?scp=84898629248&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84898629248&partnerID=8YFLogxK
U2 - 10.18632/oncoscience.3
DO - 10.18632/oncoscience.3
M3 - Article
C2 - 25593979
AN - SCOPUS:84898629248
SN - 2331-4737
VL - 1
SP - 5
EP - 13
JO - Oncoscience
JF - Oncoscience
IS - 1
ER -