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E-GEOD-84010 - 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

Status
Released on 6 July 2016, last updated on 9 July 2016
Organism
Homo sapiens
Samples (349)
Array (1)
Protocols (7)
Description
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.
Experiment type
transcription profiling by array 
Contacts
Albert Lai, Carlos Bais, Congfen Li, Frank Saran, Franklin Peale, Heidi S Phillips, Josep Garcia, Lauren E Abrey, Nicola Moore, Olivier L Chinot, Priti Hegde, Richard Bourgon, Roger Henriksson, Ryo Nishikawa, Samir Kharbanda, Thomas Sandmann, Timothy Cloughesy, Warren Mason, Wolfgang Wick
Citation
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 T, Bourgon R, Garcia J, Li C, Cloughesy T, Chinot OL, Wick W, Nishikawa R, Mason W, Henriksson R, Saran F, Lai A, Moore N, Kharbanda S, Peale F, Hegde P, Abrey LE, Phillips HS, Bais C. , PMID:26124478
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-84010.idf.txt
Sample and data relationshipE-GEOD-84010.sdrf.txt
Raw data (1)E-GEOD-84010.raw.1.zip
Processed data (1)E-GEOD-84010.processed.1.zip
Array designA-GEOD-22111.adf.txt
Links