Raising the dose of bevacizumab does not appear to add clinical benefit for adult and pediatric patients with neurofibromatosis type 2 (NF2) and progressive vestibular schwannomas. The multicenter, single-arm, phase 2 study findings were recently reported in the Journal of Clinical Oncology.1

The study (ClinicalTrials.gov identifier: NCT01767792) included 22 participants with NF2 and progressive hearing loss, of whom 15 were adults and 7 were under the age of 21. The study population include 13 females and 9 males, and the median age was 23 years (range, 12-62 years).

All study participants received bevacizumab 10 mg/kg every 2 weeks for 6 months and then bevacizumab 5 mg/kg every 3 weeks for 18 months. Hearing response defined by word recognition score at 6 months was the primary study end point.

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Overall, 41% of participants (9 of 22) had a hearing response in the target ear at 6 months, which included 8 adults and 1 child, and 32% of participants (7 of 22) had a radiographic response, all of whom were adults. In addition, 30% of participants had an improvement in NF2-related quality of life and 60% had less tinnitus-related distress.

All participants had at least 1 adverse event, with 90.9% of participants having a treatment-related grade 3 event and 13.6% having a grade 4 event. Common adverse events included hypertension (50%), fatigue (36.4%), headache (31.8%), irregular menstruation, (46.2%), and epistaxis (22.7%).

The study authors reasoned that the hearing and radiographic response rates for the study were “comparable” to those reported previously. A previous phase 2 study with a lower dose of bevacizumab showed a 36% hearing response rate and 43% radiographic response rate.

“High-dose bevacizumab seems to be no more effective than standard-dose bevacizumab for treatment of patients with NF2 with hearing loss,” the study authors wrote. “Although formal conclusions about dosing cannot be made without a randomized clinical trial, the rarity of NF2 makes such a study impractical.”


Plotkin SR, Duda DG, Muzikansky A, et al. Multicenter, prospective, phase II and biomarker study of high-dose bevacizumab as induction therapy in patients with neurofibromatosis type 2 and progressive vestibular schwannoma [published online October 18, 2019]. J Clin Oncol. doi: 10.1200/JCO.19.01367