Chinot, Olivier

Cloughesy, Timothy

Gilbert, Mark

Gorlia, Thierry

Happold, Caroline

Hegi, Monika

Mehta, Minesh

Nabors, Burt

Perry, James R.

Pugh, Stephanie L.

Reardon, David

Roth, Patrick

Stupp, Roger

Weller, Michael

Wick, Wolfgang

English

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N E U RO - O N CO LO G YAbstractsATNT-10. DOES VALPROIC ACID IMPROVE SURVIVAL INGLIOBLASTOMA? A META-ANALYSIS OF RANDOMIZEDTRIALS IN NEWLY DIAGNOSED GLIOBLASTOMACaroline Happold1, Thierry Gorlia2, Olivier Chinot3, Mark Gilbert4,Burt Nabors5, Wolfgang Wick6, Stephanie L. Pugh7, Monika Hegi8,Timothy Cloughesy9, Patrick Roth1, David Reardon10, James R. Perry11,Minesh Mehta12, Roger Stupp13, and Michael Weller1; 1Department ofNeurology, University Hospital Zurich, Zurich, Switzerland; 2EORTC DataCentre, Brussels, Belgium; 3Aix-Marseille University, Assistance Publique–Hopitaux de Marseille, Service de Neuro-Oncologie, Centre HospitalierUniversitaire Timone, Marseille, France; 4University of Texas M.D. AndersonCancer Center, Houston, TX, USA; 5University of Alabama at Birmingham,Birmingham, AL, USA; 6Neurology Clinic, University of Heidelberg &German Cancer Research Center, Heidelberg, Germany; 7NRG OncologyStatistics and Data Management Center, Philadelphia, PA, USA; 8Departmentof Clinical Neurosciences, University Hospital Lausanne, Lausanne,Switzerland; 9UCLA Neuro-Oncology Program, Los Angeles, CA, USA;10Dana-Farber Cancer Institute - Center for Neuro-Oncology, Boston, MA,USA; 11Division of Neurology, Sunnybrook Health Sciences Centre,University of Toronto, Toronto, ON, Canada; 12University of MarylandSchool of Medicine, Baltimore, MD, USA; 13Department of Oncology,University Hospital Zurich, Zurich, SwitzerlandSeveral small uncontrolled retrospective case series as well as a post-hocanalysis of the registration trial for temozolomide in newly diagnosed glioblas-toma (Weller et al., 2011) have indicated an association between valproic acid(VPA) use and improved outcome in patients with newly diagnosed glioblasto-ma. To confirm the hypothesis generated based on the analysis of the temozo-lomide registration trial, we performed a combined analysis of a survivalassociation of AED use at the start of chemoradiotherapy with temozolomidein the pooled patient cohort (n ¼ 1869) of four contemporary randomizedclinical trials in newly diagnosed glioblastoma: AVAGlio (NCT00943826),RTOG-0825 (NCT00884741), CENTRIC (NCT00689221) and CORE(NCT00813943). Progression-free (PFS) and overall survival (OS) were com-pared between (i) VPA versus no AED, (ii) VPA versus enzyme-inducing(EI)-AED, or (iii) VPA versus other non-EI-AED (without VPA). Results ofCox regression models stratified by trial and adjusted baseline prognosticfactors including O6-methylguanine DNA methyltransferase (MGMT) pro-moter methylation status were interpreted. The same analyses were performedwith levetiracetam (LEV). VPA use at the start of chemoradiotherapy was notassociated with improved PFS or OS compared with patients receiving no AED(PFS: hazard ratio (HR) ¼ 0.92, 95% confidence interval (CI) 0.75-1.13, p ¼0.41; OS: HR ¼ 1.00, 95% CI 0.80-1.25, p ¼ 0.95), EI-AED (PFS: HR ¼0.95, 95% CI 0.74-1.21, p ¼ 0.62; OS: HR ¼ 1.02, 95% CI 0.0.77-1.33,p ¼ 0.93) or non-EI-AED (PFS: HR ¼ 1.02, 95% CI 0.80-1.3, p ¼ 0.92;OS: HR ¼ 1.06, 95% CI 0.83-1.35, p ¼ 0.67). Similarly, no associationwith outcome was seen for LEV use. This pooled analysis did not validate anassociation of VPA or LEV use with improved survival, challenging the needfor a full phase III trial exploring the repurposing of VPA or LEV as add-onto the standard of care treatment of newly diagnosed glioblastoma.Neuro-Oncology 17:v10–v17, 2015.doi:10.1093/neuonc/nov205.10Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2015.

ATNT-10DOES VALPROIC ACID IMPROVE SURVIVAL IN GLIOBLASTOMA? A META-ANALYSIS OF RANDOMIZED TRIALS IN NEWLY DIAGNOSED GLIOBLASTOMA

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ATNT-10DOES VALPROIC ACID IMPROVE SURVIVAL IN GLIOBLASTOMA? A META-ANALYSIS OF RANDOMIZED TRIALS IN NEWLY DIAGNOSED GLIOBLASTOMA

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