Phase II trial of sunitinib for recurrent and progressive atypical and anaplastic meningioma

被引:209
作者
Kaley, Thomas J. [1 ]
Wen, Patrick [2 ]
Schiff, David [3 ]
Ligon, Keith [2 ]
Haider, Sam [2 ]
Karimi, Sasan [1 ]
Lassman, Andrew B. [1 ]
Nolan, Craig P. [1 ]
DeAngelis, Lisa M. [1 ]
Gavrilovic, Igor [1 ]
Norden, Andrew [2 ]
Drappatz, Jan [2 ]
Lee, Eudocia Quant [2 ]
Purow, Benjamin [3 ]
Plotkin, Scott R. [4 ]
Batchelor, Tracy [4 ]
Abrey, Lauren E. [1 ]
Omura, Antonio [1 ]
机构
[1] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10065 USA
[2] Brigham & Womens Ctr, Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA USA
[3] Univ Virginia, Dept Neurol, Charlottesville, VA USA
[4] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA
关键词
chemotherapy; malignant meningioma; sunitinib; tyrosine kinase; GROWTH-FACTOR; THERAPY; PDGF; BEVACIZUMAB; EXPRESSION; RECEPTORS; ADULTS; TUMORS; BRAIN; CELLS;
D O I
10.1093/neuonc/nou148
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 pre-treated (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.
引用
收藏
页码:116 / 121
页数:6
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