Vemurafenib achieved objective responses and durable disease control in patients with high-grade glioma.
Major finding: Vemurafenib achieved objective responses and durable disease control in patients with high-grade glioma.
Concept BRAFV600 mutations may be actionable drivers in a subset of gliomas.
Impact: Vemurafenib treatment is safe and may be effective in a subset of patients with BRAFV600-mutant glioma.
BRAFV600 mutations drive tumorigenesis in a variety of tumors including melanoma and several types of IDH1/2–wild-type glioma, making it an attractive therapeutic target. The selective BRAF inhibitor vemurafenib is approved for the treatment of BRAFV600-mutant melanoma, but it has not yet been prospectively studied for the treatment BRAFV600-mutant glioma. As part of the open-label phase II VE-BASKET study, Kaley and colleagues evaluated the safety and efficacy of vemurafenib in 24 patients with BRAFV600-mutant glioma, including 6 with glioblastoma, 5 with anaplastic astrocytoma, 7 with pleomorphic xanthoastrocytoma (PXA), 3 with anaplastic ganglioglioma, 2 with high-grade glioma, and 1 with glioma not otherwise specified. The endpoints included objective response rate, progression-free and overall survival, and toxicity. Confirmed objective responses occurred in 6 of 24 (25%) patients, with 1 complete and 2 partial responses in patients with PXA, 1 partial response in a patient with anaplastic astrocytoma, 1 partial response in a patient with pilocytic astrocytoma, and 1 partial response in a patient with anaplastic ganglioglioma. The median progression-free survival was 5.5 months and median overall survival was 28.2 months. Further, 7 of 24 patients (29%) were on treatment for at least one year. The safety profile of vemurafenib was consistent with what had previously been reported, and one patient discontinued treatment due to adverse events. Taken together, the findings from the VE-BASKET study indicate that vemurafenib is safe and has preliminary antitumor activity in BRAFV600-mutant glioma.
Kaley T, Touat M, Subbiah V, Hollebecque A, Rodon J, Lockhart AC, et al. BRAF inhibition in BRAFV600-mutant gliomas: results from the VE-BASKET study. J Clin Oncol 2018 Oct 23 [Epub ahead of print].
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