Randomized Phase II Trial of Onartuzumab in Combination With Erlotinib in Patients With Advanced Non–Small-Cell Lung Cancer

作者：David Robert Spigel, Thomas J. Ervin, Rodryg Ramlau, Davey B. Daniel, Jerome H. Goldschmidt, George R. Blumenschein, Maciej Jerzy Krzakowski, G. Robinet, B. Godbert, Fabrice Barlési, Ramaswamy Govindan, Taral Patel, С. В. Орлов, Michael S. Wertheim, Wei Yu, Jiping Zha, Robert L. Yauch, Premal H. Patel, See-Chun Phan, Amy Peterson · 发表于：Journal of Clinical Oncology · 年份：2013 · DOI：10.1200/jco.2012.47.4189 · 被引用次数：482 · 研究领域：Lung Cancer Treatments and Mutations、Liver physiology and pathology、Fibroblast Growth Factor Research

PURPOSE: Increased hepatocyte growth factor/MET signaling is associated with poor prognosis and acquired resistance to epidermal growth factor receptor (EGFR) -targeted drugs in patients with non-small-cell lung cancer (NSCLC). We investigated whether dual inhibition of MET/EGFR results in clinical benefit in patients with NSCLC. PATIENTS AND METHODS: Patients with recurrent NSCLC were randomly assigned at a ratio of one to one to receive onartuzumab plus erlotinib or placebo plus erlotinib; crossover was allowed at progression. Tumor tissue was required to assess MET status by immunohistochemistry (IHC). Coprimary end points were progression-free survival (PFS) in the intent-to-treat (ITT) and MET-positive (MET IHC diagnostic positive) populations; additional end points included overall survival (OS), objective response rate, and safety. RESULTS: There was no improvement in PFS or OS in the ITT population (n = 137; PFS hazard ratio [HR], 1.09; P = .69; OS HR, 0.80; P = .34). MET-positive patients (n = 66) treated with erlotinib plus onartuzumab showed improvement in both PFS (HR, .53; P = .04) and OS (HR, .37; P = .002). Conversely, clinical outcomes were worse in MET-negative patients treated with onartuzumab plus erlotinib (n = 62; PFS HR, 1.82; P = .05; OS HR, 1.78; P = .16). MET-positive control patients had worse outcomes versus MET-negative control patients (n = 62; PFS HR, 1.71; P = .06; OS HR, 2.61; P = .004). Incidence of peripheral edema was increased in onartuzuma...