The effectiveness of targeted therapy in the treatment of patients with neurofibromatosis type 2-related schwannomatosis and vestibular schwannomas: A systematic review.

BACKGROUND

Neurofibromatosis type 2-related schwannomatosis (NF2-SWN) is a rare genetic tumor syndrome causing progressive neurological morbidity. This systematic review evaluates current evidence on the effectiveness, safety, and patient-reported outcomes of these treatments, primarily in vestibular schwannomas.

METHODS

This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020 guidelines. Comprehensive searches of PubMed, Cochrane Library, and Google Scholar were conducted up to November 2024 using Medical Subject Headings (MeSH) and a building-block approach. Eligible studies included patients with NF2-SWN treated with targeted systemic therapies, including vascular endothelial growth factor (VEGF) inhibitors, mammalian target of rapamycin inhibitors, tyrosine kinase inhibitors (TKIs), or immunotherapies. Data extraction captured study design, population, interventions, and outcomes across four domains: radiologic response, hearing response, adverse events, and quality of life (QoL).

RESULTS

Twelve studies (6 clinical trials, 2 systematic reviews, and 4 case reports) comprising 426 patients were included. Bevacizumab was the most extensively studied agent, demonstrating durable tumor stabilization, hearing preservation, and sustained QoL with manageable long-term toxicity. Mammalian target of rapamycin inhibitors (everolimus, vistusertib) and TKIs (brigatinib, anlotinib) primarily achieved cytostatic disease control, while an early phase VEGFR peptide vaccine showed partial radiologic responses and improved subjective well-being. Across all studies, grade ≥3 toxicities were uncommon, and no treatment-related deaths occurred.

CONCLUSIONS

Targeted systemic therapy offers a disease-modifying, function-preserving alternative to surgery or radiotherapy in NF2-SWN. Although current evidence supports safety and efficacy, larger multicenter randomized trials with standardized outcome measures are required to refine dosing strategies and confirm long-term benefit.