• Thomas J Kaley, Patrick Wen, David Schiff, Keith Ligon, Sam Haidar, Sasan Karimi, Andrew B Lassman, Craig P Nolan, Lisa M DeAngelis, Igor Gavrilovic, Andrew Norden, Jan Drappatz, Eudocia Quant Lee, Benjamin Purow, Scott R Plotkin, Tracy Batchelor, Lauren E Abrey, and Antonio Omuro.
• Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York (T.J.K., S.K., A.B.L., C.P.N., L.M.D., I.G., L.E.A., A.O.); Center for Neuro-Oncology, Dana-Farber Cancer Institute/Brigham and Women's Center, Boston, Massachusetts (P.W., K.L., S.H., A.N., J.D., E.Q.L.); Department of Neurology, University of Virginia, Charlottesville, Virginia (D.S., B.P.); Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts (S.R.P., T.B.).
• Neuro-oncology. 2015 Jan 1;17(1):116-21.

BackgroundNo proven effective medical therapy for surgery and radiation-refractory meningiomas exists. Sunitinib malate (SU011248) is a small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor, abundant in meningiomas.MethodsThis was a prospective, multicenter, investigator-initiated single-arm phase II trial. The primary cohort enrolled patients with surgery and radiation-refractory recurrent World Health Organization (WHO) grades II-III meningioma. An exploratory cohort enrolled patients with WHO grade I meningioma, hemangiopericytoma, or hemangioblastoma. Sunitinib was administered at 50 mg/d for days 1-28 of every 42-day cycle. The primary endpoint was the rate of 6-month progression-free survival (PFS6), with secondary endpoints of radiographic response rate, safety, PFS, and overall survival. Exploratory objectives include analysis of tumoral molecular markers and MR perfusion imaging.ResultsThirty-six patients with high-grade meningioma (30 atypical and 6 anaplastic) were enrolled. Patients were heavily pretreated (median number of 5 recurrences, range 2-10). PFS6 rate was 42%, meeting the primary endpoint. Median PFS was 5.2 months (95% CI: 2.8-8.3 mo), and median overall survival was 24.6 months (95% CI: 16.5-38.4 mo). Thirteen patients enrolled in the exploratory cohort. Overall toxicity included 1 grade 5 intratumoral hemorrhage, 2 grade 3 and 1 grade 4 CNS/intratumoral hemorrhages, 1 grade 3 and 1 grade 4 thrombotic microangiopathy, and 1 grade 3 gastrointestinal perforation. Expression of VEGFR2 predicted PFS of a median of 1.4 months in VEGFR2-negative patients versus 6.4 months in VEGFR2-positive patients (P = .005).ConclusionSunitinib is active in recurrent atypical/malignant meningioma patients. A randomized trial should be performed.© The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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