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- Title
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.
- Authors
Wakelee, Heather; Zvirbule, Zanete; De Braud, Filippo; Kingsley, C. Daniel; Mekhail, Tarek; Lowe, Thomas; Schiitte, Wolfgang; Lena, Herve; Lawler, William; Braiteh, Fadi; Cosgriff, Thomas; Kaen, Diego; Boyer, Michelle; Jessie Hsu; Phan, See; Novello, Silvia; Schütte, Wolfgang; Lena, Hervé; Hsu, Jessie
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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%).<bold>Conclusion: </bold>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.
- Subjects
ANTINEOPLASTIC agents; ADENOCARCINOMA; CISPLATIN; COMPARATIVE studies; LONGITUDINAL method; LUNG cancer; LUNG tumors; RESEARCH methodology; MEDICAL cooperation; MONOCLONAL antibodies; PACLITAXEL; PROGNOSIS; RESEARCH; SAFETY; SURVIVAL; TUMOR classification; EVALUATION research; RANDOMIZED controlled trials; BLIND experiment; CARBOPLATIN
- Publication
Clinical Lung Cancer, 2017, Vol 18, Issue 1, p50
- ISSN
1525-7304
- Publication type
journal article
- DOI
10.1016/j.cllc.2016.09.013