TY - JOUR
T1 - Analysis of 1,115 patients tested for MET amplifi cation and therapy response in the MD anderson phase I clinic
AU - Jardim, Denis L.F.
AU - Tang, Chad
AU - Gagliato, Debora De Melo
AU - Falchook, Gerald S.
AU - Hess, Kenneth R
AU - Janku, Filip
AU - Fu, Siqing
AU - Wheler, Jennifer Jane
AU - Zinner, Ralph G
AU - Naing, Aung
AU - Tsimberidou, Apostolia M.
AU - Holla, Vijay Kumar
AU - Li, Marylin M.
AU - Roy-Chowdhuri, Sinchita
AU - Luthra, Raja
AU - Salgia, Ravi
AU - Kurzrock, Razelle
AU - Meric-Bernstam, Funda
AU - Hong, David S.
N1 - Publisher Copyright:
©2014 AACR.
PY - 2014/12/15
Y1 - 2014/12/15
N2 - Results: Of 1,115 patients, 29 (2.6%) had MET amplification. The highest prevalence was in adrenal (2 of 13; 15%) and renal (4 of 28; 14%) tumors, followed by gastroesophageal (6%), breast (5%), and ovarian cancers (4%). MET amplification was associated with adenocarcinomas (P= 0.007), high-grade tumors (P = 0.003), more sites of metastasis, higher BRAF mutation, and PTEN loss (all P < 0.05). Median overall survival was 7.23 and 8.62 months for patients with and without a MET amplification, respectively (HR = 1.12;95% confidence intervals, 0.83-1.85; P = 0.29). Among the 20 patients with MET amplification treated on a phase I protocol, 4 (20%) achieved a partial response with greatest response rate on agents targeting angiogenesis (3 of 6, 50%).Nopatient treated with a c-MET inhibitor (0 of 7) achieved an objective response.Conclusion: MET amplification was detected in 2.6% of patients with solid tumors and was associated with adenocarcinomas, high-grade histology, and higher metastatic burden. Concomitant alterations in additional pathways (BRAF mutation and PTEN loss) and variable responses on targeted therapies, including c-MET inhibitors, suggest that further studies are needed to target this population.Purpose: This study aimed to assess MET amplification among different cancers, association with clinical factors and genetic aberrations and targeted therapy response modifications.Experimental Design: From May 2010 to November 2012, samples from patients with advanced tumors referred to the MD Anderson Phase I Clinic were analyzed for MET gene amplification by FISH. Patient demographic, histologic characteristics, molecular characteristics, and outcomes in phase I protocols were compared per MET amplification status.
AB - Results: Of 1,115 patients, 29 (2.6%) had MET amplification. The highest prevalence was in adrenal (2 of 13; 15%) and renal (4 of 28; 14%) tumors, followed by gastroesophageal (6%), breast (5%), and ovarian cancers (4%). MET amplification was associated with adenocarcinomas (P= 0.007), high-grade tumors (P = 0.003), more sites of metastasis, higher BRAF mutation, and PTEN loss (all P < 0.05). Median overall survival was 7.23 and 8.62 months for patients with and without a MET amplification, respectively (HR = 1.12;95% confidence intervals, 0.83-1.85; P = 0.29). Among the 20 patients with MET amplification treated on a phase I protocol, 4 (20%) achieved a partial response with greatest response rate on agents targeting angiogenesis (3 of 6, 50%).Nopatient treated with a c-MET inhibitor (0 of 7) achieved an objective response.Conclusion: MET amplification was detected in 2.6% of patients with solid tumors and was associated with adenocarcinomas, high-grade histology, and higher metastatic burden. Concomitant alterations in additional pathways (BRAF mutation and PTEN loss) and variable responses on targeted therapies, including c-MET inhibitors, suggest that further studies are needed to target this population.Purpose: This study aimed to assess MET amplification among different cancers, association with clinical factors and genetic aberrations and targeted therapy response modifications.Experimental Design: From May 2010 to November 2012, samples from patients with advanced tumors referred to the MD Anderson Phase I Clinic were analyzed for MET gene amplification by FISH. Patient demographic, histologic characteristics, molecular characteristics, and outcomes in phase I protocols were compared per MET amplification status.
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U2 - 10.1158/1078-0432.CCR-14-1293
DO - 10.1158/1078-0432.CCR-14-1293
M3 - Article
C2 - 25326232
AN - SCOPUS:84919703143
SN - 1078-0432
VL - 20
SP - 6336
EP - 6345
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 24
ER -