Efficacy and safety of bevacizumab for vestibular schwannoma in neurofibromatosis type 2: a systematic review and meta-analysis of treatment outcomes

Background: Individual evidence suggests that the anti-angiogenic agent bevacizumab may control vestibular schwannoma (VS) growth and promote hearing preservation in patients with neurofibromatosis type 2 (NF2). However, such metadata has yet to be consolidated, as well as its side-effect profile yet to be fully understood. Our aim was to pool systematically-identified metadata in the literature and substantiate the clinical efficacy and safety of bevacizumab with respect to radiographic tumor response, hearing, and treatment outcomes. Methods: Searches of seven electronic databases from inception to March 2019 were conducted following PRISMA guidelines. Articles were screened against pre-specified criteria. The incidence of outcomes was then extracted and pooled by random-effects meta-analysis of proportions. Results: Eight articles reporting 161 NF2 patients with 196 assessable VS met satisfied all criteria. Radiographic response to bevacizumab was partial regression in 41% (95% CI 31–51%), no change in 47% (95% CI 39–55%), and tumor progression in 7% (95% CI 1–15%). In patients with assessable audiometric data, bevacizumab treatment resulted in hearing improvement in 20% (95% CI 9–33%), stability in 69% (95% CI 51–85%) and additional loss in 6% (95% CI 1–15%) Serious bevacizumab toxicity was observed in 17% (95% CI 10–26%). Subsequent surgical intervention was required in 11% (95% CI 2–20%). Conclusions: Bevacizumab may arrest both tumor progression and hearing loss in select NF2 patients presenting with VS lesions. However, a considerable proportion of patients are anticipated to experience serious adverse events; correspondingly, judicious use of bevacizumab for symptomatic management of VS in NF2 is recommended.