Phase II study of axitinib in patients with NF2-related schwannomatosis and progressive vestibular schwannomas Journal Article
| Authors: | Garcia, M. R.; Hagiwara, M.; Yaffe, A.; Mitchell, C.; Akshintala, S.; Nicolaides, T.; Phadnis, S. S.; Yohay, K.; Feng, Y.; Goldberg, J. D.; Allen, J. C.; Karajannis, M. A. |
| Article Title: | Phase II study of axitinib in patients with NF2-related schwannomatosis and progressive vestibular schwannomas |
| Abstract: | 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 ex¬ceeding 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. © 2025 The Author(s). |
| Keywords: | axitinib; vestibular schwannoma; phase 2 trial; nf2-related schwannomatosis |
| Journal Title: | Neuro-Oncology Advances |
| Volume: | 7 |
| Issue: | 1 |
| ISSN: | 2632-2498 |
| Publisher: | Oxford University Press |
| Date Published: | 2025-01-01 |
| Start Page: | vdaf083 |
| Language: | English |
| DOI: | 10.1093/noajnl/vdaf083 |
| PROVIDER: | scopus |
| PMCID: | PMC12199335 |
| PUBMED: | 40575410 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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