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). CONCLUSION: Sunitinib is active in recurrent atypical/malignant meningioma patients. A randomized trial should be performed.
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). CONCLUSION:Sunitinib is active in recurrent atypical/malignant meningiomapatients. A randomized trial should be performed.
Authors: Dirk B Mendel; A Douglas Laird; Xiaohua Xin; Sharianne G Louie; James G Christensen; Guangmin Li; Randall E Schreck; Tinya J Abrams; Theresa J Ngai; Leslie B Lee; Lesley J Murray; Jeremy Carver; Emily Chan; Katherine G Moss; Joshua O Haznedar; Juthamas Sukbuntherng; Robert A Blake; Li Sun; Cho Tang; Todd Miller; Sheri Shirazian; Gerald McMahon; Julie M Cherrington Journal: Clin Cancer Res Date: 2003-01 Impact factor: 12.531
Authors: Richard G Everson; Yuuri Hashimoto; Jacob L Freeman; Tiffany R Hodges; Jason Huse; Shouhao Zhou; Joanne Xiu; David Spetzler; Nader Sanai; Lyndon Kim; Santosh Kesari; Andrew Brenner; Franco De Monte; Amy Heimberger; Shaan M Raza Journal: J Neurooncol Date: 2018-05-30 Impact factor: 4.130
Authors: Priscilla K Brastianos; Evanthia Galanis; Nicholas Butowski; Jason W Chan; Ian F Dunn; Roland Goldbrunner; Christel Herold-Mende; Franziska M Ippen; Christian Mawrin; Michael W McDermott; Andrew Sloan; James Snyder; Ghazaleh Tabatabai; Marcos Tatagiba; Joerg C Tonn; Patrick Y Wen; Kenneth Aldape; Farshad Nassiri; Gelareh Zadeh; Michael D Jenkinson; David R Raleigh Journal: Neuro Oncol Date: 2019-01-14 Impact factor: 12.300