Treatment of progressive neurofibromatosis type 2-related vestibular schwannoma with erlotinib

Abstract

2045 Background: Neurofibromatosis type 2 (NF2) is a tumor-suppressor syndrome characterized by the presence of bilateral vestibular schwannomas (VS), which cause hearing loss, tinnitus, and imbalance. Hearing preservation rates after surgery and radiation are low (<40%). New alternatives are needed for NF2 patients with progressive tumors. Preclinical data suggests that EGFR inhibitors restore contact-dependent inhibition of growth in NF2-deficient cell lines. Methods: We performed a retrospective IRB-approved analysis on 8 NF2 patients with progressive VS who were treated with erlotinib150 mg daily. Volumetric MRI analysis was used to measure the annualized growth rate before and after erlotinib therapy and was correlated with changes in pure tone audiometry. Results: There were 5 women and 3 men with a median age of 24.5 years (range, 16 to 63 years). At baseline, 6 of 8 patients had unilateral anacusis with progressive hearing loss in the contralateral (hearing) ear due to tumor growth. Two patients with bilateral anacusis who refused surgery had progressive tumor growth causing severe brainstem. The median tumor size on the affected side was 11 cm3. Six patients were evaluable radiographically and six audiometrically with a median follow-up was 7.1 months (range, 0.5–13.6 months). The median annualized tumor growth decreased from 47% to 35.5%, and the median change in annualized tumor growth was -13.5% (range, -33% to 21%). Hearing improved in 1 patient by pure-tone thresholds and word recognition, was stable for ≥ 6months in 3 patients, and declined in 2 patients. Erlotinib was well tolerated. Rash and diarrhea (grade 1/2) developed in 7 and 5 patients, respectively, and one developed grade 2 keratitis. Conclusions: This case series suggests that erlotinib is safe and well-tolerated in NF2 patients and is associated with radiographic and audiologic responses. A phase II trial of erlotinib is planned for NF2 patients with progressive VS who are not candidates for surgery or radiation. No significant financial relationships to disclose.