Emerging systemic treatment options in meningioma

Abstract

Purpose Meningiomas are the most frequently diagnosed intracranial neoplasms. Usually, they are treated by surgical resection in curative intent. Radiotherapy and stereotactic radiosurgery are commonly applied in the adjuvant setting in newly diagnosed atypical (CNS WHO grade 2), and anaplastic (CNS WHO grade 3) meningioma, especially if gross total resection is not feasible, and in recurrent cases. Conversely, the evidence for pharmacotherapy in meningioma is scarce. Methods The available literature of systemic treatment in meningioma was screened using PubMed, and ongoing clinical trials were explored using ClinicalTrials.gov. Results Classical cytotoxic agents, somatostatin analogs, and antihormone treatments have shown only limited efficacy. In contrast, tyrosine kinase inhibitors and monoclonal antibodies, especially those targeting angiogenic signaling such as sunitinib and bevacizumab, have shown promising antitumoral activity in small phase 2 trials. Moreover, results of recent landmark studies on (epi-)genetic alterations in meningioma revealed potential therapeutic targets which are currently under investigation. These include inhibitors of mammalian target of rapamycin (mTOR), focal adhesion kinase (FAK), cyclin-dependent kinases (CDK), phosphoinositide-3-kinase (PI3K), sonic hedgehog signaling, and histone deacetylases. In addition, clinical trials evaluating immune checkpoint inhibitors such as ipilimumab, nivolumab, pembrolizumab and avelumab are currently being conducted and early results suggest clinically meaningful responses in a subset of patients. Conclusions There is a paucity of high-level evidence on systemic treatment options in meningioma. However, interesting novel treatment targets have been identified in the last decade. Positive signals of anti-angiogenic agents, genomically targeted agents and immunotherapy in early phase trials should be confirmed in large prospective controlled trials.

Advances and trends in meningioma research over the last decade: A scientometric and visual analysis

“…Secondly, radiation therapy and stereotactic radiosurgery are the other two primary management modalities after surgical meningioma resection. Related studies have included adjuvant therapy for specific types of meningiomas (e.g., atypical meningioma and mesenchymal meningioma) and their outcomes ( 5 ). In addition, we identified many studies on novel drug treatments for meningiomas in our artificial screening and statistical analysis of keywords.…”

“…Until the last decade, there has been a growing interest in the study of meningiomas, as evidenced by many studies and review articles on the subject. For instance, many attractive new therapeutic targets have been identified in the last decade ( 5 ). Various anti-angiogenic drugs, genomic-targeted drugs, and immunotherapies have performed exceptionally well in early trials ( 6 , 7 ).…”

Recurrent meningioma: When to intervene

“…Molecular mechanisms, such as cellular differentiation, cell proliferation, angiogenesis, and apoptosis, are targeted by chemotherapeutic agents (70). Unfortunately, chemotherapy treatment for recurrent meningiomas is constrained by a lack of tumor models and pre-clinical research, as well as a lack of knowledge regarding the molecular pathogenesis of meningiomas (71). For the treatment of meningiomas, numerous conventional cytotoxic agents, such as temozolomide, hydroxyurea, imatinib, trabectedin, and irinotecan, have been investigated over time (71).…”

“…Unfortunately, chemotherapy treatment for recurrent meningiomas is constrained by a lack of tumor models and pre-clinical research, as well as a lack of knowledge regarding the molecular pathogenesis of meningiomas (71). For the treatment of meningiomas, numerous conventional cytotoxic agents, such as temozolomide, hydroxyurea, imatinib, trabectedin, and irinotecan, have been investigated over time (71). However, clinical trial outcomes have typically been disappointing.…”

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

“…Following confirmation of the growth inhibition of meningioma cells in vitro, 84 a prospective study 85 treated 35 grade I meningioma patients with interferon‐α, resulting in a median time to progression of 7‐month, even though none of the patients have achieved partial or complete response to treatment. The expression of PD‐L1 (programmed death‐ligand 1) used as possible biomarkers of response to immunotherapy with immune checkpoint inhibitors as found to be present in a variable percentage of meningiomas (5%–80%), with levels of expression directly proportional to histological grading 86 . Immune checkpoint inhibitors have been tested in meningioma patients: a phase II study 87 used pembrolizumab (an anti‐PD‐1 immune checkpoint inhibitor) in 26 patients with grade II and III meningiomas and achieved a 6mPFS of 48% (90% CI: 31–66) and mOS of 20.2 months (90% CI:14.8–25.8).…”