Reliability and toxicity of bevacizumab for neurofibromatosis type 2-related vestibular schwannomas: A systematic review and meta-analysis

Am J Otolaryngol. 2021 Nov-Dec;42(6):103148. doi: 10.1016/j.amjoto.2021.103148. Epub 2021 Jun 26.

Abstract

Background: The anti-angiogenic agent bevacizumab is currently the only drug used clinically for neurofibromatosis type 2-related vestibular schwannomas (NF2-VS). Though benefits have been demonstrated in several cases, the standardized dosage remains unclear.

Objective: Our meta-analysis was performed to systematically and comprehensively investigate the reliability and toxicity of bevacizumab in the treatment of NF2-VS, with particular emphasis on the impact of dosage.

Methods: The literature search was conducted for studies providing data on patients treated with bevacizumab for NF2-VS across PubMed, Embase, and Cochrane Library until December 31, 2020. Two reviewers extracted the incidence rate of results independently. Then we calculated and pooled unadjusted incidence rate with 95% CIs for each study. The subgroups analyzed were conducted.

Results: Fourteen citations (prospective or retrospective observational cohort studies) were eligible based on data from a total of 247 patients with NF2 and 332 related VSs. The pooled results showed that the radiographic response rate (RRR) was 30% [95% CI (20%-42%)], the hearing response rate (HRR) was 32% [95% CI (21%-45%)]. The incidence of major complications was: hypertension 29% [95% CI (23%-35%)], proteinuria 30% [95% CI (18%-44%)], menstrual disorders 44% [95% CI (16%-73%)], hemorrhage 14% [95% CI (4%-26%)], grade3/4 events 12% [95% CI (4%-22%)].

Conclusions: Nearly one-third of NF2-VS patients may benefit significantly from bevacizumab due to hearing improvement and tumor reduction. Menstrual disorders were the most common adverse events. The high-dose regimen didn't show better efficacy, but results varied considerably according to age.

Keywords: Bevacizumab; Dosage; Meta-analysis; Neurofibromatosis type 2-related vestibular schwannomas.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adult
  • Age Factors
  • Bevacizumab / administration & dosage*
  • Bevacizumab / adverse effects
  • Bevacizumab / toxicity*
  • Dose-Response Relationship, Drug
  • Female
  • Hearing
  • Hemorrhage / chemically induced
  • Hemorrhage / epidemiology
  • Humans
  • Hypertension / chemically induced
  • Hypertension / epidemiology
  • Male
  • Menstruation Disturbances / chemically induced
  • Menstruation Disturbances / epidemiology
  • Neurofibromatosis 2 / diagnostic imaging
  • Neurofibromatosis 2 / drug therapy*
  • Neurofibromatosis 2 / physiopathology
  • Neuroma, Acoustic / diagnostic imaging
  • Neuroma, Acoustic / drug therapy*
  • Neuroma, Acoustic / physiopathology
  • Prospective Studies
  • Proteinuria / chemically induced
  • Proteinuria / epidemiology
  • Retrospective Studies
  • Vestibulocochlear Nerve*
  • Young Adult

Substances

  • Bevacizumab