A phase II trial of PTK787/ZK 222584 (PTK787) in recurrent high-grade meningioma.

Abstract

2046 Background: Systemic treatment options are limited for patients with recurrent meningioma. VEGF and PDGF promote angiogenesis and cellular proliferation. PTK-787 is an oral inhibitor of VEGF and PDGF receptors. The primary endpoint was to determine overall response rate. Secondary endpoints were 6-month progression-free survival (PFS-6) and overall survival. Methods: Patients (pts) with histologically confirmed recurrent WHO Grade 2 or 3 meningioma were eligible. Pts had no limit on prior therapies though must have included surgery and radiotherapy, a KPS ≥60, and were not taking enzyme inducing anticonvulsants. PTK-787 administration began at 250 mg BID and increased by 250 mg/day weekly to a dose of 500 mg BID. Clinical examinations were performed after each 4-week cycle and imaging every 8 weeks. Responses were graded using modified Macdonald criteria. Results: 21 pts were treated: 14 grade 2 and 7 grade 3 meningiomas (11 men; 10 women). Median age was 59 (29-88) years. Median KPS was 80 (60-100). Median number of cycles was 2 (range < 1-14) with one patient remaining on treatment. Main toxicities were transaminase elevation grade 4 (n=1) and 3 (n=3), fatigue grade 3 (n=4) and rash grade 3 (n=2). 3 pts were withdrawn early due to toxicity and were not evaluable for response. Best response in the remaining 17 pts was PR (n=1; 5.8%), SD (n= 12; 70.6%) and PD (n = 5; 29.4%). Overall PFS-6 and 12 was 37.5% and 12.5%; median time to progression was 3.7 m grade 2 and 3.6 m grade 3 months among the 21 pts (intent to treat). Median overall survival was 22.9 m for grade 2 and 19.6 m for grade 3. Conclusions: The combination VEGF/PDGF inhibition in pts with recurrent or progressive high-grade meningiomas can lead to disease stabilization. Targeted therapy may have a better role than cytotoxic therapies given the limited activity of available agents and suggest further studies with VEGF signaling pathway inhibition are warranted.