Efficacy and Safety of Onartuzumab in Combination With First-Line Bevacizumab- or Pemetrexed-Based Chemotherapy Regimens in Advanced Non-Squamous Non Small-Cell Lung Cancer

Based on promising early-phase data, this large randomized phase II study (n = 259) sought to determine the efficacy of onartuzumab, a monovalent monoclonal antibody targeting MET, when added to standard chemotherapy for non-squamous non small-cell lung cancer. The findings did not indicate any additional clinical benefit from the addition of onartuzumab to standard regimens in this setting, regardless of MET status. Background: Onartuzumab is a monovalent monoclonal antibody that binds with the extracellular domain of the MET receptor. Given the role of MET in non small-cell lung cancer (NSCLC), we investigated whether onartuzumab added to first-line chemotherapy efficacy in non-squamous NSCLC. Methods: Patients with untreated stage IIIB/IV non-squamous NSCLC, stratified by MET diagnostic status, were randomized to receive onartuzumab (15 mg/kg intravenously every 3 weeks) or placebo in combination with either paclitaxel/platinum/bevacizumab (bevacizumab cohort), or in combination with platinum/pemetrexed (pemetrexed cohort) with maintenance bevacizumab or pemetrexed and onartuzumab/placebo as appropriate. Co-primary endpoints of this phase II study were progression-free survival (PFS) in all patients and in MET+ patients (2+/3+), defined by the Ventana immunohistochemistry assay; secondary endpoints included overall survival (OS), objective response rate (ORR), safety, and pharmacokinetics. Results: Efficacy data were available for 139 and 120 patients in the bevacizumab and pemetrexed cohorts, respectively. No benefit was seen in the PFS endpoint in the intent-to treat population of either cohort, but was numerically worse in the onartuzumab arm of the MET-F subgroup of the bevacizumab cohort. The onartuzumab and placebo arms had similar ORR and OS results in both cohorts. A higher incidence of some adverse events was observed with onartuzumab versus placebo, including peripheral edema (30% vs. 3%, bevacizumab cohort; 48% vs. 14%, pemetrexed cohort) and venous thromboembolic events (bevacizumab cohort only, 15% vs. 6%). Conclusion: Onartuzumab does not appear to provide any additional clinical benefit when given in combination with current first-line standard-of-care chemotherapy for non-squamous NSCLC. (C) 2016 Elsevier Inc. All rights reserved.