gms | German Medical Science

Objective: Neurofibromatosis type 2 is a hereditary disorder associated with multiple neoplasms of the central and peripheral nervous system. Within the last decade, bevacizumab has emerged as a treatment option for patients who are unsuitable for (radio)surgery. The aim of this PRISMA-compliant systematic review was to synthesize available data with the goal of discovering the overall effect size on radiographic disease progression, hearing preservation and quality of life, and to assess adverse drug reactions.

Methods: The review protocol was prospectively registered with PROSPERO (CRD42017059229). Key electronic databases (Ovid Medline, Embase, Web of Science, Cochrane Library), trial registries and proceedings of relevant scientific meetings were screened for studies (both completed and ongoing) in which bevacizumab was administered to patients with confirmed NF2. All studies with at least 10 subjects, regardless of design, were considered. In case of subject overlap, data were consolidated. Two investigators conducted screening and data extraction independently. Methodological and reporting quality was assessed. In case of missing data or ambiguity, authors were contacted for information.

Results: 205 studies were screened for eligibility. 12 studies were ultimately suitable for data extraction, with an aggregate total of 153 patients. These 12 studies were derived from 5 distinct patient cohorts from 4 countries. 3/5 cohorts were retrospectively evaluated, while 2/5 were prospectively evaluated. 1/5 cohorts included patients recruited across multiple centers. Hearing remained stable or was improved in 55/60 (92%) evaluated ears over the course of treatment. Radiographic response was seen in 79/213 (37%) vestibular schwannomas and in 14/48 (29%) meningiomas. Quality of life was significantly improved in 34 evaluated patients (NFTI-QOL after six months 10.7 vs. 12.0 at baseline, p=0.05). The most common adverse events were fatigue and proteinuria (respectively n=64 and n=60 in 106 patients). The reporting quality of key methodological items was poor.

Conclusion: Bevacizumab has a differential effect on tumor volume in a select group of patients. Long-term administration appears to be associated with a number of undesirable adverse drug effects, foremost fatigue and proteinuria. The available data is based on a small number of heterogeneously reported patient cohorts. The findings of this systematic review should be validated by evidence from a high-quality multi-center double-blinded RCT.