Transcriptomics

Dataset Information

13

Patients With Proneural Glioblastoma May Derive Overall Survival Benefit From the Addition of Bevacizumab to First-Line Radiotherapy and Temozolomide: Retrospective Analysis of the AVAglio Trial


ABSTRACT: The AVAglio 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/temozolomide. To establish whether certain patient subgroups derived 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 assessed for each patient subgroup. A multivariate 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. Retrospective analysis of AVAglio data suggests that patients with IDH1 wild-type Proneural glioblastoma may derive OS benefit from first-line bevacizumab treatment. The predictive value of the Proneural subtype observed in AVAglio should be validated in an independent dataset. A total of 349 (bevacizumab arm, n = 171; placebo arm, n = 178) pretreatment specimens 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.

ORGANISM(S): Homo sapiens  

SUBMITTER: Frank Saran   Albert Lai  Congfen Li  Josep Garcia  Richard Bourgon  Warren Mason  Samir Kharbanda  Lauren E Abrey  Thomas Sandmann  Priti Hegde  Heidi S Phillips  Nicola Moore  Wolfgang Wick  Carlos Bais  Franklin Peale  Roger Henriksson  Ryo Nishikawa  Olivier L Chinot  Timothy Cloughesy 

PROVIDER: E-GEOD-84010 | ArrayExpress | 2016-07-06

SECONDARY ACCESSION(S): GSE84010PRJNA327816

REPOSITORIES: GEO, ArrayExpress

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Publications

Patients With Proneural Glioblastoma May Derive Overall Survival Benefit From the Addition of Bevacizumab to First-Line Radiotherapy and Temozolomide: Retrospective Analysis of the AVAglio Trial.

Sandmann Thomas T   Bourgon Richard R   Garcia Josep J   Li Congfen C   Cloughesy Timothy T   Chinot Olivier L OL   Wick Wolfgang W   Nishikawa Ryo R   Mason Warren W   Henriksson Roger R   Saran Frank F   Lai Albert A   Moore Nicola N   Kharbanda Samir S   Peale Franklin F   Hegde Priti P   Abrey Lauren E LE   Phillips Heidi S HS   Bais Carlos C  

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20150629 25


The 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  ...[more]

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