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

Authors: Kaley, T. J.; Wen, P.; Schiff, D.; Ligon, K.; Haidar, S.; Karimi, S.; Lassman, A. B.; Nolan, C. P.; De Angelis, L. M.; Gavrilovic, I.; Norden, A.; Drappatz, J.; Lee, E. Q.; Purow, B.; Plotkin, S. R.; Batchelor, T.; Abrey, L. E.; Omuro, A.
Article 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). Conclusion Sunitinib is active in recurrent atypical/malignant meningioma patients. A randomized trial should be performed.
Keywords: adult; cancer chemotherapy; cancer survival; clinical article; protein expression; treatment outcome; treatment response; aged; middle aged; cancer surgery; survival rate; overall survival; neutropenia; sunitinib; diarrhea; drug dose reduction; drug safety; drug withdrawal; hypertension; hypophosphatemia; multimodality cancer therapy; cancer patient; cancer radiotherapy; chemotherapy; neuroimaging; recurrence risk; brain tumor; cancer grading; prospective study; progression free survival; drug eruption; multiple cycle treatment; phase 2 clinical trial; leukopenia; stomatitis; thrombocytopenia; dehydration; qt prolongation; tumor differentiation; cohort analysis; creatinine; creatinine blood level; vasculotropin receptor 2; tumor marker; abdominal pain; alanine aminotransferase blood level; aspartate aminotransferase blood level; hyperglycemia; hyperuricemia; hypomagnesemia; lymphocytopenia; alanine aminotransferase; aspartate aminotransferase; confusion; drug induced headache; hypoalbuminemia; survival time; cerebrovascular disease; multicenter study; tumor recurrence; pancreatitis; cancer fatigue; world health organization; hemangiopericytoma; hand foot syndrome; tyrosine kinase; digestive system perforation; thrombotic thrombocytopenic purpura; tumor bleeding; tumor embolism; hemangioblastoma; dysgeusia; hypocalcemia; tumor thrombus; molecularly targeted therapy; exploratory research; malignant meningioma; brain scintiscanning; chemotherapy induced nausea and vomiting; human; male; female; article; heart right ventricle hypertrophy
Journal Title: Neuro-Oncology
Volume: 17
Issue: 1
ISSN: 1522-8517
Publisher: Oxford University Press  
Date Published: 2014-01-01
Start Page: 116
End Page: 121
Language: English
DOI: 10.1093/neuonc/nou148
PROVIDER: scopus
PUBMED: 25100872
PMCID: PMC4483051
Notes: Export Date: 2 March 2015 -- Source: Scopus
Citation Impact
MSK Authors
  1. Andrew Lassman
    111 Lassman
  2. Antonio Marcilio Padula Omuro
    202 Omuro
  3. Sasan Karimi
    108 Karimi
  4. Thomas Kaley
    134 Kaley
  5. Lauren E Abrey
    276 Abrey
  6. Craig Nolan
    55 Nolan