• Thomas Sandmann, Richard Bourgon, Josep Garcia, Congfen Li, Timothy Cloughesy, Olivier L Chinot, Wolfgang Wick, Ryo Nishikawa, Warren Mason, Roger Henriksson, Frank Saran, Albert Lai, Nicola Moore, Samir Kharbanda, Franklin Peale, Priti Hegde, Lauren E Abrey, Heidi S Phillips, and Carlos Bais.
• Thomas Sandmann, Richard Bourgon, Congfen Li, Samir Kharbanda, Franklin Peale, Priti Hegde, Heidi S. Phillips, and Carlos Bais, Genentech, South San Francisco; Timothy Cloughesy and Albert Lai, University of California Los Angeles, Los Angeles, CA; Josep Garcia, Nicola Moore, and Lauren E. Abrey F. Hoffmann-La Roche, Basel, Switzerland; Olivier L. Chinot, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille, Centre Hospitalier Universitaire Timone, Marseille, France; Wolfgang Wick, University Medical Center, Heidelberg, Germany; Ryo Nishikawa, Saitama Medical University, Saitama, Japan; Warren Mason, Princess Margaret Hospital, Toronto, Ontario, Canada; Roger Henriksson, Regional Cancer Center Stockholm, Stockholm; and Umeå University, Umeå, Sweden; and Frank Saran, Royal Marsden National Health Service Foundation Trust, Surrey, United Kingdom.
• J. Clin. Oncol. 2015 Sep 1; 33 (25): 2735-44.

PurposeThe AVAglio (Avastin in Glioblastoma) and RTOG-0825 randomized, placebo-controlled phase III trials in newly diagnosed glioblastoma reported prolonged progression-free survival (PFS), but not overall survival (OS), with the addition of bevacizumab to radiotherapy plus temozolomide. To establish whether certain patient subgroups derived an OS benefit from the addition of bevacizumab to first-line standard-of-care therapy, AVAglio patients were retrospectively evaluated for molecular subtype, and bevacizumab efficacy was assessed for each patient subgroup.Patients And MethodsA total of 349 pretreatment specimens (bevacizumab arm, n = 171; placebo arm, n = 178) from AVAglio patients (total, N = 921) were available for biomarker analysis. Samples were profiled for gene expression and isocitrate dehydrogenase 1 (IDH1) mutation status and classified into previously identified molecular subtypes. PFS and OS were assessed within each subtype.ResultsA multivariable analysis accounting for prognostic covariates revealed that bevacizumab conferred a significant OS advantage versus placebo for patients with proneural IDH1 wild-type tumors (17.1 v 12.8 months, respectively; hazard ratio, 0.43; 95% CI, 0.26 to 0.73; P = .002). This analysis also revealed an interaction between the proneural subtype biomarker and treatment arm (P = .023). The group of patients with mesenchymal and proneural tumors derived a PFS benefit from bevacizumab compared with placebo; however, this translated to an OS benefit in the proneural subset only.ConclusionRetrospective analysis of AVAglio data suggests that patients with IDH1 wild-type proneural glioblastoma may derive an OS benefit from first-line bevacizumab treatment. The predictive value of the proneural subtype observed in AVAglio should be validated in an independent data set.© 2015 by American Society of Clinical Oncology.

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