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).

Conclusion: Sunitinib is active in recurrent atypical/malignant meningioma patients. A randomized trial should be performed.

Keywords: chemotherapy; malignant meningioma; sunitinib; tyrosine kinase.

© 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.

Figures

Fig. 1.

Kaplan–Meier curves for PFS and OS: PFS6 = 44% (95% CI: 27.0–59.7); median PFS = 5.2 mo (95% CI: 2.8–8.3 mo); median OS = 24.6 mo (95% CI: 16.5–38.4 mo); 1-year OS = 79.2% (95% CI: 61.1–89.7); 2-year OS = 51.7% (95% CI: 29.4–70.4).

Fig. 2.

Kaplan–Meier curves for PFS comparing meningiomas (n = 28) with no VEGFR2 expression versus those with positive VEGFR2 expression.