Targeted Medical Therapy for Vestibular Schwannomas: Evidence, Limits, and Future Directions—A Scoping Review

TL;DR

This review evaluates the effectiveness and safety of targeted drug therapies for vestibular schwannomas, especially in patients with neurofibromatosis 2.

Contribution

The paper provides a comprehensive scoping review of targeted therapies for VSs, highlighting bevacizumab as the most effective option.

Findings

Bevacizumab showed consistent tumor control and hearing improvement with manageable side effects.

Other targeted agents like everolimus and TKIs had limited or variable efficacy.

Stopping treatment often leads to tumor rebound, suggesting the need for long-term strategies.

Abstract

Background: Vestibular schwannomas (VSs) are benign tumors that can cause significant morbidity, particularly in neurofibromatosis 2 (NF2) patients, in whom conventional treatments have important limitations. Merlin is a tumor suppressor protein encoded by the Neurofibromin 2 (NF2) gene, and the loss of its function leads to the activation of multiple signaling pathways, providing a rationale for targeted pharmacological therapies. Agents such as bevacizumab and other receptor tyrosine kinase inhibitors (TKIs) have shown variable efficacy but remain limited by toxicity and inconsistent responses. This review aims to evaluate the efficacy and safety of targeted therapies for VSs. Methods: This study was conducted according to PRISMA 2020 guidelines, using a PICO-based search of PubMed, EMBASE, and Scopus to identify studies on pharmacological therapies for VSs published between 2000 and 2025. Eligible human studies included clinical trials and observational studies reporting efficacy, safety, neuroimaging and audiological outcomes. Results: In total, 23 studies were analyzed, predominantly involving NF2-associated VSs. Treatment with bevacizumab was the most frequently investigated medical therapy and yielded the most consistent tumor control along with occasional hearing improvement, albeit with frequent but mostly manageable adverse events. Other targeted agents, including everolimus and TKIs, demonstrated limited or variable efficacy with acceptable toxicity profiles. Conclusions: VSs, particularly in NF2 patients, can cause significant morbidity and are often poorly managed by surgery or radiotherapy. Consequently, targeted medical therapies, especially anti-angiogenic agents, have emerged as valuable alternatives. Bevacizumab shows the most consistent benefits in tumor control, hearing stabilization, and quality of life, despite heterogeneous responses and notable toxicity. Evidence suggests that treatment discontinuation may lead to rapid tumor rebound, highlighting the need for long-term or maintenance strategies and careful monitoring. Future studies are needed to evaluate medical therapy integration with conventional treatments.

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