BACKGROUND: One of the hallmarks of NF2-related Schwannomatosis (NF2-related SWN) is bilateral vestibular schwannomas (VS) that can cause progressive hearing impairment in patients. This systematic review was performed to investigate the efficacy and toxicity of tested targeted agents.

METHODS: The systematic search was conducted on PubMed and EMBASE Ovid databases from inception to October 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The incidence of outcomes in studies involving bevacizumab and other targeted therapies was extracted. The bevacizumab results were pooled, and 95% confidence intervals (95% CI) were calculated.

RESULTS: Sixteen studies (8 prospective and 8 retrospective) testing 6 drugs were selected out of 721 search results. There were 10 studies concerning bevacizumab, with a total of 200 patients. The pooled radiographic response rate (RR) was 38% (95% CI: 31 - 45%) and the pooled hearing response rate (HR) was 45% (95% CI: 36 - 54%). The most frequent bevacizumab-related toxicities were hypertension and menorrhagia. Of other targeted therapies showing activity, lapatinib had a RR of 6% and a HR of 31%. A VEGFR vaccine showed RR in 29% and HR in 40% of patients. Both agents had a manageable safety profile.

CONCLUSIONS: Bevacizumab, in comparison to other targeted agents, showed the highest efficacy. Lower dosage of bevacizumab shows comparable efficacy and may reduce toxicity. Other targeted agents, administered alone or as combination therapy, have the potential to improve outcomes for VS in patients with NF2-related SWN, but future clinical studies are needed.