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

Abstract Background 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). Methods 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). Results Twelve patients were enrolled and 8 completed 12 cycles, including 2 pediatric patients. Ten patients were evaluated for the primary endpoint, defined as ≥ 20% decrease in VS volume, with 2 volumetric responses observed; both were reached after 3 cycles and sustained during treatment. The best volumetric response was −53.9% after 9 cycles. Three hearing responses were 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. Conclusions 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.