Advances in the systemic therapy for recurrent meningiomas and the challenges ahead

ABSTRACTIntroduction Meningiomas represent the most common primary neoplasms of the central nervous system (CNS). 20% present with atypical (WHO grade II) or malignant (grade III) meningiomas, which show aggressive biologic behavior and high recurrence. Although surgical resection and radiation therapy are the primary treatment options for these tumors, there is a subgroup of patients who do not respond well to or are poor candidates for these approaches, leading to the exploration of systemic therapies as an alternative.Areas covered The literature on different therapeutic groups of systemic drugs for recurrent meningiomas is reviewed, with a focus on the different molecular targets. Past and current ongoing clinical trials are also discussed.Expert opinion To date, there is no recognized treatment that has demonstrated a substantial increase in progression-free or overall survival rates. Nonetheless, therapies targeting anti-VEGF have exhibited more encouraging results in general. The examination of genomic and epigenomic traits of meningiomas, along with the integration of molecular markers into the latest WHO tumor grading system, has provided valuable insights. This has opened avenues for exploring numerous intracellular and extracellular pathways, as well as mutations, that have been targeted in ongoing clinical trials.KEYWORDS: Atypical meningiomachemotherapyhormone-directed therapymalignant meningiomarecurrent meningiomatargeted therapy Article highlights While the majority of meningiomas are benign, approximately 20% of tumors exhibit atypical characteristics and display aggressive biological behavior, making them more resistant to surgery and radiation and prone to high recurrence rates.More aggressive biological tumors have been linked to specific molecular markers, such as TERT mutations and CDKN2A/B alterations.At present, there is no well-established role for systemic therapy in the treatment of recurrent meningiomas that are not suitable for re-irradiation and for patients who are not suitable candidates for surgery.Nonetheless, anti-VEGF drugs, somatostatin analogs, and mTOR inhibitors, either alone or in combination, have the highest probability of treatment success.Molecular profiling holds significant potential for guiding the development of novel treatment strategies.Declaration of interestJ Drappatz receives royalties from Wolters Kluwer Health and Elsevier. He is also a paid consultant to Servier and receives research support from Servier and Novartis. He owns stock in Pfizer and Gilead Sciences. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Reviewer DisclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Additional informationFundingThis manuscript has not been funded.