Analysis of 1,115 Patients Tested for MET Amplification and Therapy Response in the MD Anderson Phase I Clinic

作者：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^*

来源：Clinical Cancer Research, 2014, 20(24): 6336-6345.

DOI：10.1158/1078-0432.CCR-14-1293

Purpose: This study aimed to assess MET amplification among different cancers, association with clinical factors and genetic aberrations and targeted therapy response modifications. %26lt;br%26gt;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. %26lt;br%26gt;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 %26lt; 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. %26lt;br%26gt;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.

• 出版日期2014-12-15