Phase II study of axitinib in patients with NF2-related schwannomatosis and progressive vestibular schwannomas

Axitinib is an oral multi-receptor tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor receptor (PDGFR), and c-KIT. These represent a clinically and/or preclinically validated molecular targets in vestibular schwannoma (VS).

Eligible patients were age >5 years with a clinical diagnosis of NF2-related schwannomatosis (NF2-SWN) and at least one volumetrically measurable, progressive VS. Axitinib was given continuously in 28-day cycles for up to of 12 cycles. Primary endpoint was objective volumetric response rate to axitinib, hearing response was a secondary endpoint, along with validated quality of life assessments (NFTI-QOL).

Twelve patients were enrolled and eight completed 12 cycles, including two pediatric patients. Ten patients were evaluable for the primary endpoint, defined as ≥20% decrease in VS volume, with two volumetric responses observed; both were reached after three cycles and sustained during treatment. Best volumetric response was −53.9% after nine cycles. Three hearing responses observed, one of which was sustained during treatment. All patients experienced drug-related toxicities, the most common were diarrhea, hematuria and skin toxicity, not exceeding grade 2, as well as hypertension, not exceeding grade 3. NFTI-QOL scores remained stable or improved during treatment.

Axitinib therapy targeting VEGFR, PDGFR and c-KIT is feasible in this population and associated with volumetric and hearing responses in a subset of patients. However, convenience of oral administration should be balanced with respect to efficacy and safety of axitinib in comparison with other molecular targeted therapies, including intravenous bevacizumab.