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.

Clin Lung Cancer 2017 01 19;18(1):50-59. Epub 2016 Oct 19.

Department of Oncology, AOU San Luigi-Orbassano, University of Turin, Turin, Italy.

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+ 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.

Download full-text PDF

Source
https://linkinghub.elsevier.com/retrieve/pii/S15257304163024
Publisher Site
http://dx.doi.org/10.1016/j.cllc.2016.09.013DOI Listing
January 2017

Publication Analysis

Top Keywords

bevacizumab cohort
16
non-squamous nsclc
8
pemetrexed cohort
8
bevacizumab pemetrexed
8
non-small-cell lung
8
onartuzumab
8
lung cancer
8
cohort
7
bevacizumab
6
pemetrexed onartuzumab/placebo
4
higher incidence
4
incidence adverse
4
onartuzumab placebo
4
cohort onartuzumab
4
study progression-free
4
onartuzumab/placebo appropriate
4
cohorts higher
4
arms orr
4
orr cohorts
4
appropriate co-primary
4

Similar Publications