title: Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase II Study of Onartuzumab Plus Bevacizumab Versus Placebo Plus Bevacizumab in Patients With Recurrent Glioblastoma: Efficacy, Safety, and Hepatocyte Growth Factor and O6-Methylguanine-DNA Methyltransferase Biomarker Analyses.
abstract: Purpose Bevacizumab regimens are approved for the treatment of recurrent glioblastoma in many countries. Aberrant mesenchymal-epithelial transition factor (MET) expression has been reported in glioblastoma and may contribute to bevacizumab resistance. The phase II study GO27819 investigated the monovalent MET inhibitor onartuzumab plus bevacizumab (Ona + Bev) versus placebo plus bevacizumab (Pla + Bev) in recurrent glioblastoma. Methods At first recurrence after chemoradiation, bevacizumab-naïve patients with glioblastoma were randomly assigned 1:1 to receive Ona (15 mg/kg, once every 3 weeks) + Bev (15 mg/kg, once every 3 weeks) or Pla + Bev until disease progression. The primary end point was progression-free survival by response assessment in neuro-oncology criteria. Secondary end points were overall survival, objective response rate, duration of response, and safety. Exploratory biomarker analyses correlated efficacy with expression levels of MET ligand hepatocyte growth factor, O6-methylguanine-DNA methyltransferase promoter methylation, and glioblastoma subtype. Results Among 129 patients enrolled (Ona + Bev, n = 64; Pla + Bev, n = 65), baseline characteristics were balanced. The median progression-free survival was 3.9 months for Ona + Bev versus 2.9 months for Pla + Bev (hazard ratio, 1.06; 95% CI, 0.72 to 1.56; P = .7444). The median overall survival was 8.8 months for Ona + Bev and 12.6 months for Pla + Bev (hazard ratio, 1.45; 95% CI, 0.88 to 2.37; P = .1389). Grade ≥ 3 adverse events were reported in 38.5% of patients who received Ona + Bev and 35.9% of patients who received Pla + Bev. Exploratory biomarker analyses suggested that patients with high expression of hepatocyte growth factor or unmethylated O6-methylguanine-DNA methyltransferase may benefit from Ona + Bev. Conclusion There was no evidence of further clinical benefit with the addition of onartuzumab to bevacizumab compared with bevacizumab plus placebo in unselected patients with recurrent glioblastoma in this phase II study; however, further investigation into biomarker subgroups is warranted.
authors.affiliation: Timothy Cloughesy, University of California, Los Angeles; Lawrence Recht, Stanford Cancer Center, Stanford; Carlos Bais, Thomas Sandmann, Jean-Marie Bruey, Hartmut Koeppen, Bo Liu, Wendy Verret, See-Chun Phan, and David S. Shames, Genentech, South San Francisco, CA; Tom Mikkelsen, Henry Ford Hospital, Detroit, MI; Gaetano Finocchiaro, Istituto Neurologico Carlo Besta, Milan; Alba A. Brandes, Azienda Unità Sanitaria Locale-Istituto di Ricovero e Cura a Carattere Scientifico Institute of Neurologic Sciences, Bologna, Italy; Cristóbal Belda-Iniesta, Centro Integral Oncológico Clara Campal, University Hospital HM Sanchinarro, Madrid; Estela Pineda, Hospital Clinic of Barcelona; Carmen Balana, Institut Català d'Oncologia Badalona Hospital Germans Trias I Pujol, Barcelona, Spain; Olivier L. Chinot, Aix-Marseille Université Assistance Publique-Hôpitaux de Marseille, Marseille, France; David R. Macdonald, London Health Sciences Centre, London, Ontario, Canada; Manfred Westphal, University Clinic Hamburg-Eppendorf, Hamburg, Germany; Kirsten Hopkins, Bristol Haematology and Oncology Centre, Bristol, United Kingdom; and Michael Weller, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Timothy
authors.initials: T
authors.lastname: Cloughesy
authors.affiliation: Timothy Cloughesy, University of California, Los Angeles; Lawrence Recht, Stanford Cancer Center, Stanford; Carlos Bais, Thomas Sandmann, Jean-Marie Bruey, Hartmut Koeppen, Bo Liu, Wendy Verret, See-Chun Phan, and David S. Shames, Genentech, South San Francisco, CA; Tom Mikkelsen, Henry Ford Hospital, Detroit, MI; Gaetano Finocchiaro, Istituto Neurologico Carlo Besta, Milan; Alba A. Brandes, Azienda Unità Sanitaria Locale-Istituto di Ricovero e Cura a Carattere Scientifico Institute of Neurologic Sciences, Bologna, Italy; Cristóbal Belda-Iniesta, Centro Integral Oncológico Clara Campal, University Hospital HM Sanchinarro, Madrid; Estela Pineda, Hospital Clinic of Barcelona; Carmen Balana, Institut Català d'Oncologia Badalona Hospital Germans Trias I Pujol, Barcelona, Spain; Olivier L. Chinot, Aix-Marseille Université Assistance Publique-Hôpitaux de Marseille, Marseille, France; David R. Macdonald, London Health Sciences Centre, London, Ontario, Canada; Manfred Westphal, University Clinic Hamburg-Eppendorf, Hamburg, Germany; Kirsten Hopkins, Bristol Haematology and Oncology Centre, Bristol, United Kingdom; and Michael Weller, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Finocchiaro
authors.affiliation: Timothy Cloughesy, University of California, Los Angeles; Lawrence Recht, Stanford Cancer Center, Stanford; Carlos Bais, Thomas Sandmann, Jean-Marie Bruey, Hartmut Koeppen, Bo Liu, Wendy Verret, See-Chun Phan, and David S. Shames, Genentech, South San Francisco, CA; Tom Mikkelsen, Henry Ford Hospital, Detroit, MI; Gaetano Finocchiaro, Istituto Neurologico Carlo Besta, Milan; Alba A. Brandes, Azienda Unità Sanitaria Locale-Istituto di Ricovero e Cura a Carattere Scientifico Institute of Neurologic Sciences, Bologna, Italy; Cristóbal Belda-Iniesta, Centro Integral Oncológico Clara Campal, University Hospital HM Sanchinarro, Madrid; Estela Pineda, Hospital Clinic of Barcelona; Carmen Balana, Institut Català d'Oncologia Badalona Hospital Germans Trias I Pujol, Barcelona, Spain; Olivier L. Chinot, Aix-Marseille Université Assistance Publique-Hôpitaux de Marseille, Marseille, France; David R. Macdonald, London Health Sciences Centre, London, Ontario, Canada; Manfred Westphal, University Clinic Hamburg-Eppendorf, Hamburg, Germany; Kirsten Hopkins, Bristol Haematology and Oncology Centre, Bristol, United Kingdom; and Michael Weller, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Cristóbal
authors.initials: C
authors.lastname: Belda-Iniesta
authors.affiliation: Timothy Cloughesy, University of California, Los Angeles; Lawrence Recht, Stanford Cancer Center, Stanford; Carlos Bais, Thomas Sandmann, Jean-Marie Bruey, Hartmut Koeppen, Bo Liu, Wendy Verret, See-Chun Phan, and David S. Shames, Genentech, South San Francisco, CA; Tom Mikkelsen, Henry Ford Hospital, Detroit, MI; Gaetano Finocchiaro, Istituto Neurologico Carlo Besta, Milan; Alba A. Brandes, Azienda Unità Sanitaria Locale-Istituto di Ricovero e Cura a Carattere Scientifico Institute of Neurologic Sciences, Bologna, Italy; Cristóbal Belda-Iniesta, Centro Integral Oncológico Clara Campal, University Hospital HM Sanchinarro, Madrid; Estela Pineda, Hospital Clinic of Barcelona; Carmen Balana, Institut Català d'Oncologia Badalona Hospital Germans Trias I Pujol, Barcelona, Spain; Olivier L. Chinot, Aix-Marseille Université Assistance Publique-Hôpitaux de Marseille, Marseille, France; David R. Macdonald, London Health Sciences Centre, London, Ontario, Canada; Manfred Westphal, University Clinic Hamburg-Eppendorf, Hamburg, Germany; Kirsten Hopkins, Bristol Haematology and Oncology Centre, Bristol, United Kingdom; and Michael Weller, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Recht
authors.affiliation: Timothy Cloughesy, University of California, Los Angeles; Lawrence Recht, Stanford Cancer Center, Stanford; Carlos Bais, Thomas Sandmann, Jean-Marie Bruey, Hartmut Koeppen, Bo Liu, Wendy Verret, See-Chun Phan, and David S. Shames, Genentech, South San Francisco, CA; Tom Mikkelsen, Henry Ford Hospital, Detroit, MI; Gaetano Finocchiaro, Istituto Neurologico Carlo Besta, Milan; Alba A. Brandes, Azienda Unità Sanitaria Locale-Istituto di Ricovero e Cura a Carattere Scientifico Institute of Neurologic Sciences, Bologna, Italy; Cristóbal Belda-Iniesta, Centro Integral Oncológico Clara Campal, University Hospital HM Sanchinarro, Madrid; Estela Pineda, Hospital Clinic of Barcelona; Carmen Balana, Institut Català d'Oncologia Badalona Hospital Germans Trias I Pujol, Barcelona, Spain; Olivier L. Chinot, Aix-Marseille Université Assistance Publique-Hôpitaux de Marseille, Marseille, France; David R. Macdonald, London Health Sciences Centre, London, Ontario, Canada; Manfred Westphal, University Clinic Hamburg-Eppendorf, Hamburg, Germany; Kirsten Hopkins, Bristol Haematology and Oncology Centre, Bristol, United Kingdom; and Michael Weller, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Alba A
authors.initials: AA
authors.lastname: Brandes
authors.affiliation: Timothy Cloughesy, University of California, Los Angeles; Lawrence Recht, Stanford Cancer Center, Stanford; Carlos Bais, Thomas Sandmann, Jean-Marie Bruey, Hartmut Koeppen, Bo Liu, Wendy Verret, See-Chun Phan, and David S. Shames, Genentech, South San Francisco, CA; Tom Mikkelsen, Henry Ford Hospital, Detroit, MI; Gaetano Finocchiaro, Istituto Neurologico Carlo Besta, Milan; Alba A. Brandes, Azienda Unità Sanitaria Locale-Istituto di Ricovero e Cura a Carattere Scientifico Institute of Neurologic Sciences, Bologna, Italy; Cristóbal Belda-Iniesta, Centro Integral Oncológico Clara Campal, University Hospital HM Sanchinarro, Madrid; Estela Pineda, Hospital Clinic of Barcelona; Carmen Balana, Institut Català d'Oncologia Badalona Hospital Germans Trias I Pujol, Barcelona, Spain; Olivier L. Chinot, Aix-Marseille Université Assistance Publique-Hôpitaux de Marseille, Marseille, France; David R. Macdonald, London Health Sciences Centre, London, Ontario, Canada; Manfred Westphal, University Clinic Hamburg-Eppendorf, Hamburg, Germany; Kirsten Hopkins, Bristol Haematology and Oncology Centre, Bristol, United Kingdom; and Michael Weller, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Estela
authors.initials: E
authors.lastname: Pineda
authors.affiliation: Timothy Cloughesy, University of California, Los Angeles; Lawrence Recht, Stanford Cancer Center, Stanford; Carlos Bais, Thomas Sandmann, Jean-Marie Bruey, Hartmut Koeppen, Bo Liu, Wendy Verret, See-Chun Phan, and David S. Shames, Genentech, South San Francisco, CA; Tom Mikkelsen, Henry Ford Hospital, Detroit, MI; Gaetano Finocchiaro, Istituto Neurologico Carlo Besta, Milan; Alba A. Brandes, Azienda Unità Sanitaria Locale-Istituto di Ricovero e Cura a Carattere Scientifico Institute of Neurologic Sciences, Bologna, Italy; Cristóbal Belda-Iniesta, Centro Integral Oncológico Clara Campal, University Hospital HM Sanchinarro, Madrid; Estela Pineda, Hospital Clinic of Barcelona; Carmen Balana, Institut Català d'Oncologia Badalona Hospital Germans Trias I Pujol, Barcelona, Spain; Olivier L. Chinot, Aix-Marseille Université Assistance Publique-Hôpitaux de Marseille, Marseille, France; David R. Macdonald, London Health Sciences Centre, London, Ontario, Canada; Manfred Westphal, University Clinic Hamburg-Eppendorf, Hamburg, Germany; Kirsten Hopkins, Bristol Haematology and Oncology Centre, Bristol, United Kingdom; and Michael Weller, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Tom
authors.initials: T
authors.lastname: Mikkelsen
authors.affiliation: Timothy Cloughesy, University of California, Los Angeles; Lawrence Recht, Stanford Cancer Center, Stanford; Carlos Bais, Thomas Sandmann, Jean-Marie Bruey, Hartmut Koeppen, Bo Liu, Wendy Verret, See-Chun Phan, and David S. Shames, Genentech, South San Francisco, CA; Tom Mikkelsen, Henry Ford Hospital, Detroit, MI; Gaetano Finocchiaro, Istituto Neurologico Carlo Besta, Milan; Alba A. Brandes, Azienda Unità Sanitaria Locale-Istituto di Ricovero e Cura a Carattere Scientifico Institute of Neurologic Sciences, Bologna, Italy; Cristóbal Belda-Iniesta, Centro Integral Oncológico Clara Campal, University Hospital HM Sanchinarro, Madrid; Estela Pineda, Hospital Clinic of Barcelona; Carmen Balana, Institut Català d'Oncologia Badalona Hospital Germans Trias I Pujol, Barcelona, Spain; Olivier L. Chinot, Aix-Marseille Université Assistance Publique-Hôpitaux de Marseille, Marseille, France; David R. Macdonald, London Health Sciences Centre, London, Ontario, Canada; Manfred Westphal, University Clinic Hamburg-Eppendorf, Hamburg, Germany; Kirsten Hopkins, Bristol Haematology and Oncology Centre, Bristol, United Kingdom; and Michael Weller, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Olivier L
authors.initials: OL
authors.lastname: Chinot
authors.affiliation: Timothy Cloughesy, University of California, Los Angeles; Lawrence Recht, Stanford Cancer Center, Stanford; Carlos Bais, Thomas Sandmann, Jean-Marie Bruey, Hartmut Koeppen, Bo Liu, Wendy Verret, See-Chun Phan, and David S. Shames, Genentech, South San Francisco, CA; Tom Mikkelsen, Henry Ford Hospital, Detroit, MI; Gaetano Finocchiaro, Istituto Neurologico Carlo Besta, Milan; Alba A. Brandes, Azienda Unità Sanitaria Locale-Istituto di Ricovero e Cura a Carattere Scientifico Institute of Neurologic Sciences, Bologna, Italy; Cristóbal Belda-Iniesta, Centro Integral Oncológico Clara Campal, University Hospital HM Sanchinarro, Madrid; Estela Pineda, Hospital Clinic of Barcelona; Carmen Balana, Institut Català d'Oncologia Badalona Hospital Germans Trias I Pujol, Barcelona, Spain; Olivier L. Chinot, Aix-Marseille Université Assistance Publique-Hôpitaux de Marseille, Marseille, France; David R. Macdonald, London Health Sciences Centre, London, Ontario, Canada; Manfred Westphal, University Clinic Hamburg-Eppendorf, Hamburg, Germany; Kirsten Hopkins, Bristol Haematology and Oncology Centre, Bristol, United Kingdom; and Michael Weller, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Carmen
authors.initials: C
authors.lastname: Balana
authors.affiliation: Timothy Cloughesy, University of California, Los Angeles; Lawrence Recht, Stanford Cancer Center, Stanford; Carlos Bais, Thomas Sandmann, Jean-Marie Bruey, Hartmut Koeppen, Bo Liu, Wendy Verret, See-Chun Phan, and David S. Shames, Genentech, South San Francisco, CA; Tom Mikkelsen, Henry Ford Hospital, Detroit, MI; Gaetano Finocchiaro, Istituto Neurologico Carlo Besta, Milan; Alba A. Brandes, Azienda Unità Sanitaria Locale-Istituto di Ricovero e Cura a Carattere Scientifico Institute of Neurologic Sciences, Bologna, Italy; Cristóbal Belda-Iniesta, Centro Integral Oncológico Clara Campal, University Hospital HM Sanchinarro, Madrid; Estela Pineda, Hospital Clinic of Barcelona; Carmen Balana, Institut Català d'Oncologia Badalona Hospital Germans Trias I Pujol, Barcelona, Spain; Olivier L. Chinot, Aix-Marseille Université Assistance Publique-Hôpitaux de Marseille, Marseille, France; David R. Macdonald, London Health Sciences Centre, London, Ontario, Canada; Manfred Westphal, University Clinic Hamburg-Eppendorf, Hamburg, Germany; Kirsten Hopkins, Bristol Haematology and Oncology Centre, Bristol, United Kingdom; and Michael Weller, University Hospital Zurich, Zurich, Switzerland.
authors.forename: David R
authors.initials: DR
authors.lastname: Macdonald
authors.affiliation: Timothy Cloughesy, University of California, Los Angeles; Lawrence Recht, Stanford Cancer Center, Stanford; Carlos Bais, Thomas Sandmann, Jean-Marie Bruey, Hartmut Koeppen, Bo Liu, Wendy Verret, See-Chun Phan, and David S. Shames, Genentech, South San Francisco, CA; Tom Mikkelsen, Henry Ford Hospital, Detroit, MI; Gaetano Finocchiaro, Istituto Neurologico Carlo Besta, Milan; Alba A. Brandes, Azienda Unità Sanitaria Locale-Istituto di Ricovero e Cura a Carattere Scientifico Institute of Neurologic Sciences, Bologna, Italy; Cristóbal Belda-Iniesta, Centro Integral Oncológico Clara Campal, University Hospital HM Sanchinarro, Madrid; Estela Pineda, Hospital Clinic of Barcelona; Carmen Balana, Institut Català d'Oncologia Badalona Hospital Germans Trias I Pujol, Barcelona, Spain; Olivier L. Chinot, Aix-Marseille Université Assistance Publique-Hôpitaux de Marseille, Marseille, France; David R. Macdonald, London Health Sciences Centre, London, Ontario, Canada; Manfred Westphal, University Clinic Hamburg-Eppendorf, Hamburg, Germany; Kirsten Hopkins, Bristol Haematology and Oncology Centre, Bristol, United Kingdom; and Michael Weller, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Manfred
authors.initials: M
authors.lastname: Westphal
authors.affiliation: Timothy Cloughesy, University of California, Los Angeles; Lawrence Recht, Stanford Cancer Center, Stanford; Carlos Bais, Thomas Sandmann, Jean-Marie Bruey, Hartmut Koeppen, Bo Liu, Wendy Verret, See-Chun Phan, and David S. Shames, Genentech, South San Francisco, CA; Tom Mikkelsen, Henry Ford Hospital, Detroit, MI; Gaetano Finocchiaro, Istituto Neurologico Carlo Besta, Milan; Alba A. Brandes, Azienda Unità Sanitaria Locale-Istituto di Ricovero e Cura a Carattere Scientifico Institute of Neurologic Sciences, Bologna, Italy; Cristóbal Belda-Iniesta, Centro Integral Oncológico Clara Campal, University Hospital HM Sanchinarro, Madrid; Estela Pineda, Hospital Clinic of Barcelona; Carmen Balana, Institut Català d'Oncologia Badalona Hospital Germans Trias I Pujol, Barcelona, Spain; Olivier L. Chinot, Aix-Marseille Université Assistance Publique-Hôpitaux de Marseille, Marseille, France; David R. Macdonald, London Health Sciences Centre, London, Ontario, Canada; Manfred Westphal, University Clinic Hamburg-Eppendorf, Hamburg, Germany; Kirsten Hopkins, Bristol Haematology and Oncology Centre, Bristol, United Kingdom; and Michael Weller, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Hopkins
authors.affiliation: Timothy Cloughesy, University of California, Los Angeles; Lawrence Recht, Stanford Cancer Center, Stanford; Carlos Bais, Thomas Sandmann, Jean-Marie Bruey, Hartmut Koeppen, Bo Liu, Wendy Verret, See-Chun Phan, and David S. Shames, Genentech, South San Francisco, CA; Tom Mikkelsen, Henry Ford Hospital, Detroit, MI; Gaetano Finocchiaro, Istituto Neurologico Carlo Besta, Milan; Alba A. Brandes, Azienda Unità Sanitaria Locale-Istituto di Ricovero e Cura a Carattere Scientifico Institute of Neurologic Sciences, Bologna, Italy; Cristóbal Belda-Iniesta, Centro Integral Oncológico Clara Campal, University Hospital HM Sanchinarro, Madrid; Estela Pineda, Hospital Clinic of Barcelona; Carmen Balana, Institut Català d'Oncologia Badalona Hospital Germans Trias I Pujol, Barcelona, Spain; Olivier L. Chinot, Aix-Marseille Université Assistance Publique-Hôpitaux de Marseille, Marseille, France; David R. Macdonald, London Health Sciences Centre, London, Ontario, Canada; Manfred Westphal, University Clinic Hamburg-Eppendorf, Hamburg, Germany; Kirsten Hopkins, Bristol Haematology and Oncology Centre, Bristol, United Kingdom; and Michael Weller, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
authors.affiliation: Timothy Cloughesy, University of California, Los Angeles; Lawrence Recht, Stanford Cancer Center, Stanford; Carlos Bais, Thomas Sandmann, Jean-Marie Bruey, Hartmut Koeppen, Bo Liu, Wendy Verret, See-Chun Phan, and David S. Shames, Genentech, South San Francisco, CA; Tom Mikkelsen, Henry Ford Hospital, Detroit, MI; Gaetano Finocchiaro, Istituto Neurologico Carlo Besta, Milan; Alba A. Brandes, Azienda Unità Sanitaria Locale-Istituto di Ricovero e Cura a Carattere Scientifico Institute of Neurologic Sciences, Bologna, Italy; Cristóbal Belda-Iniesta, Centro Integral Oncológico Clara Campal, University Hospital HM Sanchinarro, Madrid; Estela Pineda, Hospital Clinic of Barcelona; Carmen Balana, Institut Català d'Oncologia Badalona Hospital Germans Trias I Pujol, Barcelona, Spain; Olivier L. Chinot, Aix-Marseille Université Assistance Publique-Hôpitaux de Marseille, Marseille, France; David R. Macdonald, London Health Sciences Centre, London, Ontario, Canada; Manfred Westphal, University Clinic Hamburg-Eppendorf, Hamburg, Germany; Kirsten Hopkins, Bristol Haematology and Oncology Centre, Bristol, United Kingdom; and Michael Weller, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Carlos
authors.initials: C
authors.lastname: Bais
authors.affiliation: Timothy Cloughesy, University of California, Los Angeles; Lawrence Recht, Stanford Cancer Center, Stanford; Carlos Bais, Thomas Sandmann, Jean-Marie Bruey, Hartmut Koeppen, Bo Liu, Wendy Verret, See-Chun Phan, and David S. Shames, Genentech, South San Francisco, CA; Tom Mikkelsen, Henry Ford Hospital, Detroit, MI; Gaetano Finocchiaro, Istituto Neurologico Carlo Besta, Milan; Alba A. Brandes, Azienda Unità Sanitaria Locale-Istituto di Ricovero e Cura a Carattere Scientifico Institute of Neurologic Sciences, Bologna, Italy; Cristóbal Belda-Iniesta, Centro Integral Oncológico Clara Campal, University Hospital HM Sanchinarro, Madrid; Estela Pineda, Hospital Clinic of Barcelona; Carmen Balana, Institut Català d'Oncologia Badalona Hospital Germans Trias I Pujol, Barcelona, Spain; Olivier L. Chinot, Aix-Marseille Université Assistance Publique-Hôpitaux de Marseille, Marseille, France; David R. Macdonald, London Health Sciences Centre, London, Ontario, Canada; Manfred Westphal, University Clinic Hamburg-Eppendorf, Hamburg, Germany; Kirsten Hopkins, Bristol Haematology and Oncology Centre, Bristol, United Kingdom; and Michael Weller, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Sandmann
authors.affiliation: Timothy Cloughesy, University of California, Los Angeles; Lawrence Recht, Stanford Cancer Center, Stanford; Carlos Bais, Thomas Sandmann, Jean-Marie Bruey, Hartmut Koeppen, Bo Liu, Wendy Verret, See-Chun Phan, and David S. Shames, Genentech, South San Francisco, CA; Tom Mikkelsen, Henry Ford Hospital, Detroit, MI; Gaetano Finocchiaro, Istituto Neurologico Carlo Besta, Milan; Alba A. Brandes, Azienda Unità Sanitaria Locale-Istituto di Ricovero e Cura a Carattere Scientifico Institute of Neurologic Sciences, Bologna, Italy; Cristóbal Belda-Iniesta, Centro Integral Oncológico Clara Campal, University Hospital HM Sanchinarro, Madrid; Estela Pineda, Hospital Clinic of Barcelona; Carmen Balana, Institut Català d'Oncologia Badalona Hospital Germans Trias I Pujol, Barcelona, Spain; Olivier L. Chinot, Aix-Marseille Université Assistance Publique-Hôpitaux de Marseille, Marseille, France; David R. Macdonald, London Health Sciences Centre, London, Ontario, Canada; Manfred Westphal, University Clinic Hamburg-Eppendorf, Hamburg, Germany; Kirsten Hopkins, Bristol Haematology and Oncology Centre, Bristol, United Kingdom; and Michael Weller, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Bruey
authors.affiliation: Timothy Cloughesy, University of California, Los Angeles; Lawrence Recht, Stanford Cancer Center, Stanford; Carlos Bais, Thomas Sandmann, Jean-Marie Bruey, Hartmut Koeppen, Bo Liu, Wendy Verret, See-Chun Phan, and David S. Shames, Genentech, South San Francisco, CA; Tom Mikkelsen, Henry Ford Hospital, Detroit, MI; Gaetano Finocchiaro, Istituto Neurologico Carlo Besta, Milan; Alba A. Brandes, Azienda Unità Sanitaria Locale-Istituto di Ricovero e Cura a Carattere Scientifico Institute of Neurologic Sciences, Bologna, Italy; Cristóbal Belda-Iniesta, Centro Integral Oncológico Clara Campal, University Hospital HM Sanchinarro, Madrid; Estela Pineda, Hospital Clinic of Barcelona; Carmen Balana, Institut Català d'Oncologia Badalona Hospital Germans Trias I Pujol, Barcelona, Spain; Olivier L. Chinot, Aix-Marseille Université Assistance Publique-Hôpitaux de Marseille, Marseille, France; David R. Macdonald, London Health Sciences Centre, London, Ontario, Canada; Manfred Westphal, University Clinic Hamburg-Eppendorf, Hamburg, Germany; Kirsten Hopkins, Bristol Haematology and Oncology Centre, Bristol, United Kingdom; and Michael Weller, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Koeppen
authors.affiliation: Timothy Cloughesy, University of California, Los Angeles; Lawrence Recht, Stanford Cancer Center, Stanford; Carlos Bais, Thomas Sandmann, Jean-Marie Bruey, Hartmut Koeppen, Bo Liu, Wendy Verret, See-Chun Phan, and David S. Shames, Genentech, South San Francisco, CA; Tom Mikkelsen, Henry Ford Hospital, Detroit, MI; Gaetano Finocchiaro, Istituto Neurologico Carlo Besta, Milan; Alba A. Brandes, Azienda Unità Sanitaria Locale-Istituto di Ricovero e Cura a Carattere Scientifico Institute of Neurologic Sciences, Bologna, Italy; Cristóbal Belda-Iniesta, Centro Integral Oncológico Clara Campal, University Hospital HM Sanchinarro, Madrid; Estela Pineda, Hospital Clinic of Barcelona; Carmen Balana, Institut Català d'Oncologia Badalona Hospital Germans Trias I Pujol, Barcelona, Spain; Olivier L. Chinot, Aix-Marseille Université Assistance Publique-Hôpitaux de Marseille, Marseille, France; David R. Macdonald, London Health Sciences Centre, London, Ontario, Canada; Manfred Westphal, University Clinic Hamburg-Eppendorf, Hamburg, Germany; Kirsten Hopkins, Bristol Haematology and Oncology Centre, Bristol, United Kingdom; and Michael Weller, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Timothy Cloughesy, University of California, Los Angeles; Lawrence Recht, Stanford Cancer Center, Stanford; Carlos Bais, Thomas Sandmann, Jean-Marie Bruey, Hartmut Koeppen, Bo Liu, Wendy Verret, See-Chun Phan, and David S. Shames, Genentech, South San Francisco, CA; Tom Mikkelsen, Henry Ford Hospital, Detroit, MI; Gaetano Finocchiaro, Istituto Neurologico Carlo Besta, Milan; Alba A. Brandes, Azienda Unità Sanitaria Locale-Istituto di Ricovero e Cura a Carattere Scientifico Institute of Neurologic Sciences, Bologna, Italy; Cristóbal Belda-Iniesta, Centro Integral Oncológico Clara Campal, University Hospital HM Sanchinarro, Madrid; Estela Pineda, Hospital Clinic of Barcelona; Carmen Balana, Institut Català d'Oncologia Badalona Hospital Germans Trias I Pujol, Barcelona, Spain; Olivier L. Chinot, Aix-Marseille Université Assistance Publique-Hôpitaux de Marseille, Marseille, France; David R. Macdonald, London Health Sciences Centre, London, Ontario, Canada; Manfred Westphal, University Clinic Hamburg-Eppendorf, Hamburg, Germany; Kirsten Hopkins, Bristol Haematology and Oncology Centre, Bristol, United Kingdom; and Michael Weller, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Wendy
authors.initials: W
authors.lastname: Verret
authors.affiliation: Timothy Cloughesy, University of California, Los Angeles; Lawrence Recht, Stanford Cancer Center, Stanford; Carlos Bais, Thomas Sandmann, Jean-Marie Bruey, Hartmut Koeppen, Bo Liu, Wendy Verret, See-Chun Phan, and David S. Shames, Genentech, South San Francisco, CA; Tom Mikkelsen, Henry Ford Hospital, Detroit, MI; Gaetano Finocchiaro, Istituto Neurologico Carlo Besta, Milan; Alba A. Brandes, Azienda Unità Sanitaria Locale-Istituto di Ricovero e Cura a Carattere Scientifico Institute of Neurologic Sciences, Bologna, Italy; Cristóbal Belda-Iniesta, Centro Integral Oncológico Clara Campal, University Hospital HM Sanchinarro, Madrid; Estela Pineda, Hospital Clinic of Barcelona; Carmen Balana, Institut Català d'Oncologia Badalona Hospital Germans Trias I Pujol, Barcelona, Spain; Olivier L. Chinot, Aix-Marseille Université Assistance Publique-Hôpitaux de Marseille, Marseille, France; David R. Macdonald, London Health Sciences Centre, London, Ontario, Canada; Manfred Westphal, University Clinic Hamburg-Eppendorf, Hamburg, Germany; Kirsten Hopkins, Bristol Haematology and Oncology Centre, Bristol, United Kingdom; and Michael Weller, University Hospital Zurich, Zurich, Switzerland.
authors.forename: See-Chun
authors.initials: SC
authors.lastname: Phan
authors.affiliation: Timothy Cloughesy, University of California, Los Angeles; Lawrence Recht, Stanford Cancer Center, Stanford; Carlos Bais, Thomas Sandmann, Jean-Marie Bruey, Hartmut Koeppen, Bo Liu, Wendy Verret, See-Chun Phan, and David S. Shames, Genentech, South San Francisco, CA; Tom Mikkelsen, Henry Ford Hospital, Detroit, MI; Gaetano Finocchiaro, Istituto Neurologico Carlo Besta, Milan; Alba A. Brandes, Azienda Unità Sanitaria Locale-Istituto di Ricovero e Cura a Carattere Scientifico Institute of Neurologic Sciences, Bologna, Italy; Cristóbal Belda-Iniesta, Centro Integral Oncológico Clara Campal, University Hospital HM Sanchinarro, Madrid; Estela Pineda, Hospital Clinic of Barcelona; Carmen Balana, Institut Català d'Oncologia Badalona Hospital Germans Trias I Pujol, Barcelona, Spain; Olivier L. Chinot, Aix-Marseille Université Assistance Publique-Hôpitaux de Marseille, Marseille, France; David R. Macdonald, London Health Sciences Centre, London, Ontario, Canada; Manfred Westphal, University Clinic Hamburg-Eppendorf, Hamburg, Germany; Kirsten Hopkins, Bristol Haematology and Oncology Centre, Bristol, United Kingdom; and Michael Weller, University Hospital Zurich, Zurich, Switzerland.
authors.forename: David S
authors.initials: DS
authors.lastname: Shames
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality; D059248:Chemoradiotherapy; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality; D017228:Hepatocyte Growth Factor / Q000032:analysis*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; C066855:HGF protein, human; D025521:Tumor Suppressor Proteins; D000068258:Bevacizumab; D017228:Hepatocyte Growth Factor; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; C584058:onartuzumab