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

Abstract

PurposeBRAFV600 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 MethodsThe 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.ResultsTwenty-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.ConclusionVemurafenib 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.

Low-grade developmental and epilepsy associated brain tumors: a critical update 2020

“…The notion that BRAF V600E mutations are pharmacologically addressable by nextgeneration kinase inhibitors, such as Vemurafenib, open an important new avenue for personalized medicine in gangliogliomas difficult to approach surgically, i.e. in the dominant hemisphere and close to eloquent cortical regions, or with histopathologically atypical or anaplastic features [27,39,76].…”

Pan-Cancer Efficacy of Vemurafenib in BRAFV600-Mutant Non-Melanoma Cancers

“…Expanded enrollment of patients with Erdheim-Chester disease ultimately resulted in regulatory approval of vemurafenib in this indication in the United States (14). Subsequently, more mature data in NSCLC (15), primary brain tumors (16), and myeloma (17) have been published.…”

Spinal cord anaplastic astrocytoma with BRAF V600E mutation: A case report and review of literature

“…Recently, molecular therapy targeting the BRAF V600E mutation has been applied in clinical practice for malignant melanomas and other types of malignant tumors . For intracranial HGGs, the efficacy of BRAF inhibitors has been reported in laboratory and clinical studies . Although genetic analysis has been performed in several cases of spinal cord HGGs, most reports did not describe the BRAF V600E .…”