• Timothy Cloughesy, Gaetano Finocchiaro, Cristóbal Belda-Iniesta, Lawrence Recht, Alba A Brandes, Estela Pineda, Tom Mikkelsen, Olivier L Chinot, Carmen Balana, David R Macdonald, Manfred Westphal, Kirsten Hopkins, Michael Weller, Carlos Bais, Thomas Sandmann, Jean-Marie Bruey, Hartmut Koeppen, Bo Liu, Wendy Verret, See-Chun Phan, and David S Shames.
• 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.
• J. Clin. Oncol. 2017 Jan 20; 35 (3): 343-351.

AbstractPurpose 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.

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