Data from Analysis of 1,115 Patients Tested for <i>MET</i> Amplification and Therapy Response in the MD Anderson Phase I Clinic

Abstract

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; This study aimed to assess &lt;i&gt;MET&lt;/i&gt; amplification among different cancers, association with clinical factors and genetic aberrations and targeted therapy response modifications.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; From May 2010 to November 2012, samples from patients with advanced tumors referred to the MD Anderson Phase I Clinic were analyzed for &lt;i&gt;MET&lt;/i&gt; gene amplification by FISH. Patient demographic, histologic characteristics, molecular characteristics, and outcomes in phase I protocols were compared per &lt;i&gt;MET&lt;/i&gt; amplification status.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Of 1,115 patients, 29 (2.6%) had &lt;i&gt;MET&lt;/i&gt; 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%). &lt;i&gt;MET&lt;/i&gt; amplification was associated with adenocarcinomas (&lt;i&gt;P&lt;/i&gt; = 0.007), high-grade tumors (&lt;i&gt;P&lt;/i&gt; = 0.003), more sites of metastasis, higher &lt;i&gt;BRAF&lt;/i&gt; mutation, and PTEN loss (all &lt;i&gt;P&lt;/i&gt; &lt; 0.05). Median overall survival was 7.23 and 8.62 months for patients with and without a &lt;i&gt;MET&lt;/i&gt; amplification, respectively (HR = 1.12; 95% confidence intervals, 0.83–1.85; &lt;i&gt;P&lt;/i&gt; = 0.29). Among the 20 patients with &lt;i&gt;MET&lt;/i&gt; 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.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusion:&lt;/b&gt;&lt;i&gt;MET&lt;/i&gt; 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 (&lt;i&gt;BRAF&lt;/i&gt; mutation and PTEN loss) and variable responses on targeted therapies, including c-MET inhibitors, suggest that further studies are needed to target this population. &lt;i&gt;Clin Cancer Res; 20(24); 6336–45. ©2014 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;