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.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 ¼ 0.007), high-grade tumors (P ¼ 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 ¼ 1.12; 95% confidence intervals, 0.83-1.85; P ¼ 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.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. Clin Cancer Res; 20(24); 6336-45. Ó2014 AACR.

<p>Table S1 - Histologies and tumor grade by site according to MET amplification status. Table S2- Type of BRAF mutations by tumor site. Table S3 - List of phase I trials included as best trials for MET amplified patients.</p>

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

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

<p>Table S1 - Histologies and tumor grade by site according to MET amplification status. Table S2- Type of BRAF mutations by tumor site. Table S3 - List of phase I trials included as best trials for MET amplified patients.</p>