Erlotinib for Progressive Vestibular Schwannoma in Neurofibromatosis 2 Patients

Abstract

In vitro treatment of Nf2-deficient cells with epidermal growth factor receptor (EGFR) inhibitors can inhibit cellular proliferation. We retrospectively assessed the effect of erlotinib (150 mg daily) on eleven consecutive NF2 patients with progressive VS who were poor candidates for standard therapy. A radiographic response was defined as ≥ 20% decrease in tumor volume compared to baseline. A hearing response was defined as a statistically significant increase in word recognition score (WRS) compared to baseline; a minor hearing response was defined as a 10 dB improvement in pure-tone average with stable WRS. Before treatment, the median and mean annual volumetric growth rate for eleven index VS were 26% and 46%, respectively. Among 10 evaluable patients, the median time-to-tumor progression was 9.2 months. Three patients with stable disease experienced maximum tumor shrinkage of 4%, 13%, and 14%. Nine patients underwent audiologic evaluations. One experienced a transient hearing response, two experienced minor hearing responses, three remained stable, and two developed progressive hearing loss. The median time-to-progressive hearing loss was 9.2 months and to either tumor growth or progressive hearing loss was 7.1 months. Adverse treatment effects included mild-to-moderate rash, diarrhea, and hair thinning, with 2 episodes of grade 3 toxicity. Erlotinib treatment was not associated with radiographic or hearing responses in NF2 patients with progressive VS. Because a subset of patients experienced prolonged stable disease, time-to-progression may be more appropriate than radiographic or hearing response for anti-EGFR agents in NF2-associated VS.