A multi-institutional phase II trial of bevacizumab for recurrent and refractory meningioma

Abstract

Background Systemic therapies for refractory meningiomas are limited with no FDA approved therapeutics. Vascular endothelial growth factor (VEGF) is a signaling protein associated with neovascularization, peritumoral edema, and meningioma tumorigenesis. Methods This phase II study investigates the efficacy of bevacizumab (BEV), a VEGF binding monoclonal antibody, in patients with progressive Grade I (G1M), Grade II (G2M), Grade III (G3M) meningioma, and other non-parenchymal tumors including vestibular schwannoma (n=4) and hemangiopericytoma (HPC) (n=4) with primary endpoint of PFS-6. Non-meningiomas were included with the respective meningioma grade in analysis. Secondary endpoints include median overall survival (mOS), and response rate. Results 50 patients (26 women; median age 54 years; range 23-81), 42 with of progressive meningioma) were treated: 10 G1M, 20 G2M, and 12 G3M. Prior treatments include surgical resection (41 patients), radiosurgery (24 patients), external beam radiotherapy (28 patients) and chemotherapy (14 patients). Median infusions administered was 16 (range, 2-68). Response was graded using the Macdonald criteria. PFS-6, mPFS, and mOS were 87%, 22 months, 35 months for G1M; 77%, 23 months, 41 months for G2M, and 46%, 8 months, 12 months for G3M. Best radiographic responses include stable disease (G1M: 100%; G2M: 85%; G3M: 82%); partial response (G1M: 0%; G2M: 5%; G3M: 0%) and progressive disease (G1M: 0%; G2M: 10%; G3M:18%). The most common toxicities were hypertension (n=19, 42.2%), proteinuria (n=16, 35.6%), and fatigue (n=14, 31.1%). Conclusion This study showed BEV is well tolerated and appears to be a promising systemic treatment option for patients with recurrent and refractory meningiomas.

Noncoding RNA landscape and their emerging roles as biomarkers and therapeutic targets in meningioma

“…Bevacizumab, a monoclonal anti-VEGF receptor antibody, showed promise in a phase II clinical trial for recurrent and refractory meningiomas, leading to longer PFS of meningioma patients. 143 As observed through longitudinal imaging analyses, bevacizumab has been associated with meningioma growth inhibition and reduced peritumoral edema. 144 A phase II trial of bevacizumab in combination with the mTOR inhibitor everolimus showed mild improvement in the PFS of meningioma patients.…”

The molecular biology of NF2/Merlin on tumorigenesis and development

“…The dynamic contrast enhanced‐magnetic resonance imaging (DCE‐MRI) results indicate that Bevacizumab has the potential to enhance blood circulation and oxygen delivery by reinstating the proper functioning of blood vessels in tumors, which demonstrated effective results in tumor edema decrease in a schwannoma murine model 128 . Another study has shown that postsurgery and radiosurgery treatment with Bevacizumab stabilized grade I, II, and III meningiomas with survival rates of higher than 45% 129 …”

“…128 Another study has shown that postsurgery and radiosurgery treatment with Bevacizumab stabilized grade I, II, and III meningiomas with survival rates of higher than 45%. 129 4.1.2 | PDGFRs PDGFRs' activity in VS cells is hindered through the Imatinib Mesylate treatment, resulting in an enhanced cell sustenance, depending on the dose usage. Additionally, Imatinib Mesylate can inhibit the development of both tumors and new blood vessels NF2-mediated VS disease, which makes it an appropriate prospect for additional clinical studies targeting schwannoma.…”

The role of radiation therapy and systemic treatments in meningioma: The present and the future

“… 80 Fifteen patients were treated: the best radiological response was SD, with a 6mPFS of 43.8% (95% CI: 15.7–69.1). One of the few phase II studies evaluating bevacizumab in 50 patients with meningioma was recently published by Kumthekar et al 81 The study involved 10 patients with grade I, 20 with grade II, and 12 with grade III meningiomas. The 6mPFS was 87%, 77%, and 46% for grade I, II, III meningiomas respectively.…”