title: Phase II trial of sunitinib for recurrent and progressive atypical and anaplastic meningioma.
abstract: BACKGROUND
  No 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.
  
  
  METHODS
  This 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.
  
  
  RESULTS
  Thirty-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).
  
  
  CONCLUSIONS
  Sunitinib is active in recurrent atypical/malignant meningioma patients. A randomized trial should be performed.
authors.affiliation: 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.).
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kaley
authors.affiliation: 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.).
authors.forename: Patrick
authors.initials: P
authors.lastname: Wen
authors.affiliation: 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.).
authors.forename: David
authors.initials: D
authors.lastname: Schiff
authors.affiliation: 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.).
authors.forename: Keith
authors.initials: K
authors.lastname: Ligon
authors.affiliation: 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.).
authors.forename: Sam
authors.initials: S
authors.lastname: Haidar
authors.affiliation: 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.).
authors.forename: Sasan
authors.initials: S
authors.lastname: Karimi
authors.affiliation: 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.).
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Lassman
authors.affiliation: 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.).
authors.forename: Craig P
authors.initials: CP
authors.lastname: Nolan
authors.affiliation: 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.).
authors.forename: Lisa M
authors.initials: LM
authors.lastname: DeAngelis
authors.affiliation: 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.).
authors.forename: Igor
authors.initials: I
authors.lastname: Gavrilovic
authors.affiliation: 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.).
authors.forename: Andrew
authors.initials: A
authors.lastname: Norden
authors.affiliation: 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.).
authors.forename: Jan
authors.initials: J
authors.lastname: Drappatz
authors.affiliation: 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.).
authors.forename: Eudocia Quant
authors.initials: EQ
authors.lastname: Lee
authors.affiliation: 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.).
authors.forename: Benjamin
authors.initials: B
authors.lastname: Purow
authors.affiliation: 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.).
authors.forename: Scott R
authors.initials: SR
authors.lastname: Plotkin
authors.affiliation: 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.).
authors.forename: Tracy
authors.initials: T
authors.lastname: Batchelor
authors.affiliation: 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.).
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Abrey
authors.affiliation: 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.).
authors.forename: Antonio
authors.initials: A
authors.lastname: Omuro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008577:Meningeal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008579:Meningioma / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
keywords: chemotherapy; malignant meningioma; sunitinib; tyrosine kinase
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