Analysis of 1,115 patients tested for MET amplification and therapy response in the MD Anderson Phase I clinic
A partir d'échantillons prélevés sur 1 115 patients atteints d'une tumeur de stade avancé et inclus dans un essai de phase I au Centre MD Anderson, cette étude évalue la prévalence des tumeurs présentant une amplification du gène MET, puis analyse, pour les patients concernés, la réponse à un inhibiteur de c-MET
Purpose: Assess MET amplification among different cancers, association with clinical factors and genetic aberrations and targeted therapy response modifications. Experimental Design: From 05/2010 to 11/2012 samples from patients with advanced tumors referred to the Phase I Clinic were analyzed for MET gene amplification by fluorescence in situ hybridization. Patient demographic, histologic, 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=0.007) and high-grade tumors (P=0.003), more sites of metastasis and 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 (hazard ratio [HR] = 1.12; 95% CI, 0.83 to 1.85; P=.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 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.