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.
abstract: 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.
  
  
  
  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.
  
  
  
  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%).
  
  
  
  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.
authors.affiliation: Division of Oncology, Department of Medicine, Stanford University, Stanford, CA. Electronic address: hwakelee@stanford.edu.
authors.forename: Heather
authors.initials: H
authors.lastname: Wakelee
authors.affiliation: Medical Oncology Department, Riga Eastern Clinical University Hospital, Latvian Oncology Center, Riga, Latvia.
authors.forename: Zanete
authors.initials: Z
authors.lastname: Zvirbule
authors.affiliation: Medical Oncology Department, National Cancer Institute of Milan, Milan, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: De Braud
authors.affiliation: Clearview Cancer Institute, Huntsville, AL.
authors.forename: C Daniel
authors.initials: CD
authors.lastname: Kingsley
authors.affiliation: Department of Hematology/Oncology, Florida Hospital, Orlando, FL.
authors.forename: Tarek
authors.initials: T
authors.lastname: Mekhail
authors.affiliation: Department of Medical Oncology, Cancer Care Associates Medical Group, Inc, Redondo Beach, CA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lowe
authors.affiliation: Department of Internal Medicine II, Martha-Maria Krankenhaus Halle-Dölau gGmbH, Halle, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schütte
authors.affiliation: Pneumology Service, Hôpital Pontchaillou, Rennes, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Lena
authors.affiliation: St Jude Heritage Medical Group, Fullerton, CA.
authors.forename: William
authors.initials: W
authors.lastname: Lawler
authors.affiliation: Department of Medical Oncology, Comprehensive Cancer Centers of Nevada, Henderson, NV.
authors.forename: Fadi
authors.initials: F
authors.lastname: Braiteh
authors.affiliation: Division of Hematology/Oncology, Crescent City Research Consortium, Marrero, LA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Cosgriff
authors.affiliation: Centro Oncologico Riojano Integral (CORI), La Rioja, Argentina.
authors.forename: Diego
authors.initials: D
authors.lastname: Kaen
authors.affiliation: Department of Clinical Science, F. Hoffmann-La Roche Ltd, Welwyn Garden City, UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: Boyer
authors.affiliation: Biostatistics Department, Product Development Oncology, Genentech Inc., San Francisco, CA.
authors.forename: Jessie
authors.initials: J
authors.lastname: Hsu
authors.affiliation: Biostatistics Department, Product Development Oncology, Genentech Inc., San Francisco, CA.
authors.forename: See
authors.initials: S
authors.lastname: Phan
authors.affiliation: Department of Oncology, AOU San Luigi-Orbassano, University of Turin, Turin, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Novello
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D000068437:Pemetrexed / Q000008:administration & dosage; D011379:Prognosis; D012449:Safety; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D000068437:Pemetrexed; D000068258:Bevacizumab; D016190:Carboplatin; C584058:onartuzumab; D017239:Paclitaxel; D002945:Cisplatin
keywords: Biomarkers; Combination therapy; MET; Phase II clinical trial; Progression-free survival