title: Efficacy and Safety Results From a Phase II, Placebo-Controlled Study of Onartuzumab Plus First-Line Platinum-Doublet Chemotherapy for Advanced Squamous Cell Non-Small-Cell Lung Cancer.
abstract: The treatment options for squamous cell non-small-cell lung cancer (NSCLC) are limited. We assessed the efficacy and safety of onartuzumab plus platinum-doublet chemotherapy in previously untreated advanced squamous cell NSCLC.
  
  
  
  The patients were randomized to receive onartuzumab plus paclitaxel plus carboplatin/cisplatin (n = 55) or placebo plus paclitaxel plus carboplatin/cisplatin (n = 54). Randomization was stratified by MET diagnostic status: MET immunohistochemistry (IHC)-positive (MET IHC 3+/2+) or MET IHC-negative (MET IHC 1+/0). The co-primary endpoints were investigator-assessed progression-free survival in the intent-to-treat and the MET IHC+populations.
  
  
  
  The risk of disease progression or death was similar between the 2 treatment arms in both the intent-to-treat (stratified hazard ratio, 0.95; 95% confidence interval, 0.63-1.43) and MET IHC+populations (unstratified hazard ratio, 1.27; 95% confidence interval, 0.69-2.32). Comparable results were obtained for overall survival and the objective response rate. In all safety-evaluable patients, the grade 3 to 5 adverse events occurring at a > 5% greater incidence in the onartuzumab-containing versus the placebo-containing arm were neutropenia (14.8% vs. 5.8%) and pulmonary embolism (5.6% vs. 0%). Eight patients died as a result of adverse events: 1 case each of pneumonitis, pneumonia, cardiac failure, and unexplained death in the onartuzumab arm and 1 case each of hemorrhage, cardiac arrest, hemoptysis, and febrile neutropenia in the placebo arm.
  
  
  
  Studies using alternative assays of MET activation might help to clarify the role of onartuzumab. However, with the lack of clinical activity seen in the present study, the development of onartuzumab for squamous cell NSCLC will not be pursued further.
authors.affiliation: Medicine and Pathology, University of Colorado Cancer Center, Denver, CO. Electronic address: Fred.Hirsch@ucdenver.edu.
authors.forename: Fred R
authors.initials: FR
authors.lastname: Hirsch
authors.affiliation: Division of Oncology, Washington University, St. Louis, MO.
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Govindan
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: Department of Translational Oncology, Comprehensive Cancer Centers of Nevada, Henderson, NV.
authors.forename: Fadi
authors.initials: F
authors.lastname: Braiteh
authors.affiliation: Lungenfachklinik Immenhausen, Thoracic Oncology, Immenhausen, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Rittmeyer
authors.affiliation: Medical Oncology Division, Centro Integral Oncológico Clara Campal, Madrid, Spain.
authors.forename: Cristóbal
authors.initials: C
authors.lastname: Belda-Iniesta
authors.affiliation: Medical Oncology Department, Hospital Universitario Lozano Blesa, Zaragoza, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Isla
authors.affiliation: Division of Hematology-Oncology, Crescent City Research Consortium, Marrero, LA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Cosgriff
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: Oncology Biostatistics, Genentech Inc, South San Francisco, CA.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Ueda
authors.affiliation: Product Development Oncology, Genentech Inc, South San Francisco, CA.
authors.forename: See
authors.initials: S
authors.lastname: Phan
authors.affiliation: Division of Hematology-Oncology, University of California Davis Cancer Center, Sacramento, CA.
authors.forename: David R
authors.initials: DR
authors.lastname: Gandara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / 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; D011379:Prognosis; D012449:Safety; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D016190:Carboplatin; C584058:onartuzumab; D017239:Paclitaxel; D002945:Cisplatin
keywords: Immunohistochemistry; MET signaling; NSCLC; Poor prognosis; Squamous cell carcinoma