BRAF Inhibition in BRAF V600 -Mutant Gliomas: Results From the VE-BASKET Study - Sorbonne Université Access content directly
Journal Articles Journal of Clinical Oncology Year : 2018

BRAF Inhibition in BRAF V600 -Mutant Gliomas: Results From the VE-BASKET Study

Vivek Subbiah
  • Function : Author

Abstract

Purpose: BRAFV600 mutations are frequently found in several glioma subtypes, including pleomorphic xanthoastrocytoma (PXA) and ganglioglioma and much less commonly in glioblastoma. We sought to determine the activity of vemurafenib, a selective inhibitor of BRAFV600, in patients with gliomas that harbor this mutation. Patients and methods: The VE-BASKET study was an open-label, nonrandomized, multicohort study for BRAFV600-mutant nonmelanoma cancers. Patients with BRAFV600-mutant glioma received vemurafenib 960 mg twice per day continuously until disease progression, withdrawal, or intolerable adverse effects. Key end points included confirmed objective response rate by RECIST version 1.1, progression-free survival, overall survival, and safety. Results: Twenty-four patients (median age, 32 years; 18 female and six male patients) with glioma, including malignant diffuse glioma (n = 11; six glioblastoma and five anaplastic astrocytoma), PXA (n = 7), anaplastic ganglioglioma (n = 3), pilocytic astrocytoma (n = 2), and high-grade glioma, not otherwise specified (n = 1), were treated. Confirmed objective response rate was 25% (95% CI, 10% to 47%) and median progression-free survival was 5.5 months (95% CI, 3.7 to 9.6 months). In malignant diffuse glioma, best response included one partial response and five patients with stable disease, two of whom had disease stabilization that lasted more than 1 year. In PXA, best response included one complete response, two partial responses, and three patients with stable disease. Additional partial responses were observed in patients with pilocytic astrocytoma and anaplastic ganglioglioma (one each). The safety profile of vemurafenib was generally consistent with that of previously published studies. Conclusion: Vemurafenib demonstrated evidence of durable antitumor activity in some patients with BRAFV600-mutant gliomas, although efficacy seemed to vary qualitatively by histologic subtype. Additional study is needed to determine the optimal use of vemurafenib in patients with primary brain tumors and to identify the mechanisms driving differential responses across histologic subsets.
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Dates and versions

hal-04541090 , version 1 (10-04-2024)

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Thomas Kaley, Mehdi Touat, Vivek Subbiah, Antoine Hollebecque, Jordi Rodon, et al.. BRAF Inhibition in BRAF V600 -Mutant Gliomas: Results From the VE-BASKET Study. Journal of Clinical Oncology, 2018, 36 (35), pp.3477-3484. ⟨10.1200/JCO.2018.78.9990⟩. ⟨hal-04541090⟩
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