Analysis of 1,115 patients tested for MET amplification and therapy response in the MD Anderson Phase I Clinic

• Published in: Clinical cancer research 2014-12, Vol.20 (24), p.6336-6345
• Main Authors: Jardim, Denis L F, Tang, Chad, Gagliato, Debora De Melo, Falchook, Gerald S, Hess, Kenneth, Janku, Filip, Fu, Siqing, Wheler, Jennifer J, Zinner, Ralph G, Naing, Aung, Tsimberidou, Apostolia M, Holla, Vijaykumar, Li, Marylin M, Roy-Chowdhuri, Sinchita, Luthra, Raja, Salgia, Ravi, Kurzrock, Razelle, Meric-Bernstam, Funda, Hong, David S
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Clinical Trials, Phase I as Topic; Female; Gene Amplification; Humans; Male; Middle Aged; Molecular Targeted Therapy; Mutation; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging; Neoplasms - genetics; Neoplasms - mortality; Neoplasms - pathology; Neoplasms - therapy; Prognosis; Proto-Oncogene Proteins c-met - genetics; Texas; Treatment Outcome; Young Adult
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.ccr-14-1293

This study aimed to assess MET amplification among different cancers, association with clinical factors and genetic aberrations and targeted therapy response modifications. 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. 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%). No patient treated with a c-MET inhibitor (0 of 7) achieved an objective response. 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.