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.

• Authors: 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, Antonio Omuro
• Journal: Neuro-oncology (Neuro Oncol) Vol. 17 Issue 1 Pg. 116-21 (Jan 2015) ISSN: 1523-5866 [Electronic] England
• PMID: 25100872 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 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: [email protected].

Chemical References

• Antineoplastic Agents
• Indoles
• Pyrroles
• Sunitinib

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (adverse effects, therapeutic use)
• Cohort Studies
• Disease-Free Survival
• Female
• Humans
• Indoles (adverse effects, therapeutic use)
• Kaplan-Meier Estimate
• Male
• Meningeal Neoplasms (drug therapy, mortality)
• Meningioma (drug therapy, mortality)
• Middle Aged
• Pyrroles (adverse effects, therapeutic use)
• Sunitinib
• Treatment Outcome