Systemic therapy in the treatment of recurrent or refractory intracranial meningiomas: A systematic review and individual patient data meta-analysis

Recurrent or refractory meningiomas pose major therapeutic challenges once surgical and radiotherapeutic options are exhausted. The role and comparative effectiveness of systemic pharmacologic therapies remain unclear. This study evaluated survival outcomes and toxicity profiles of systemic agents used in adults with recurrent intracranial meningiomas. A systematic search of PubMed, Embase, and Web of Science (through November 2024) followed PRISMA-IPD guidelines. Eligible studies included adults with WHO grades I-III meningiomas treated with systemic agents for recurrent disease and reporting reconstructable time-to-event data. Individual patient data and digitized Kaplan–Meier estimates were pooled. Outcomes included progression-free survival (PFS), overall survival (OS), and treatment-related toxicity. Twenty-five studies (484 patients) were included. Across systemic agents, outcomes predominantly reflected disease stabilization rather than objective tumor regression. Hydroxyurea (n = 8) was most frequently evaluated, followed by bevacizumab (5), somatostatin analogues (5), interferon-α (3), PD-1/PD-L1 inhibitors (2), and tyrosine kinase inhibitors (2). Median PFS varied widely by WHO grade, with longer PFS generally observed in grade 1 tumors. Interferon-α and somatostatin analogs demonstrated longer PFS in grade 1 compared with higher-grade tumors Median OS ranged from 8 to 32 months without grade-specific differences. Toxicity profiles differed by agent: hydroxyurea was associated with frequent hematologic adverse effects (67.4%,), while bevacizumab and somatostatin analogs were generally well tolerated with low discontinuation rates. Hydroxyurea, interferon-α, and somatostatin analogues offer modest disease stabilization, particularly in lower-grade tumors, with generally manageable toxicity. These findings provide pooled, non-comparative benchmark reference ranges for future systemic therapy trials in recurrent/refractory meningioma.