Avastin for NF2 Vestibular Schwannomas

And another thing that Avastin (bevacizumab; Genentech) may be good for:

The anti-VEGF monoclonal antibody improved hearing loss and reduced tumor volume in patients with growing vestibular schwannomas. The conclusions are based on data from a small, first-of-its-kind study of patients with neurofibromatosis (NF) type 2—data which are available in an early release article from The NEJM.

Ten consecutive patients with NF type 2 and progressive vestibular schwannomas (who were not candidates for or declined the standard treatment of surgery and radiation therapy*) received at least one dose of bevacizumab (5 mg/kg every 2 weeks). The median annual growth rate of schwannomas before treatment was 62%, and the median duration of treatment was 12 months. (The rationale for assessing bevacizumab in NF-associated schwannomas is based on the expression of VEGF in tumor cells. However, the expression of the VEGF receptor, VEGFR-2, on tumor vessels is not particularly high—which suggests that an anti-VEGF-receptor drug is less likely to be of benefit than bevacizumab.)

In a retrospective analysis, 9/10 tumors shrank (best median response, 26% reduction) after bevacizumab treatment, and 6 demonstrated an imaging response. Only 1 patient experienced an increase in tumor volume (of 32%). Tumor reduction strongly correlated with baseline vasogenic edema on MR images (ie, the mean apparent diffusion coefficent). Improvements in hearing (at <12 weeks) were observed in 5 of 7 eligible patients and were progressive and durable (up to 16 months) in most.

This pilot study was not funded by Genentech; although 1 author (Gregory Sorensen, MD) reported receiving grant support from the company.

NF2 is a dominantly inherited disorder with a prevalence of 1 in 25,000. The most common tumor type associated with the condition is vestibular (or acoustic) schwannomas, benign tumors of the 8th cranial nerve. Growth of tumors causes progressive hearing loss, as does surgical and radiation therapy. Progressive vestibular schwannomas can also produce brainstem compression.

In May, the FDA approved Avastin for the treatment of the uniformly fatal brain tumor, glioblastoma multiforme, after standard therapy.

VEGF = vascular endothelial-cell growth factor.

* Eight patients were at high risk for complete hearing loss with standard therapy.