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|Ref Type||Journal Article|
|Authors||Kaley T, Touat M, Subbiah V, Hollebecque A, Rodon J, Lockhart AC, Keedy V, Bielle F, Hofheinz RD, Joly F, Blay JY, Chau I, Puzanov I, Raje NS, Wolf J, DeAngelis LM, Makrutzki M, Riehl T, Pitcher B, Baselga J, Hyman DM|
|Title||BRAF Inhibition in BRAFV600-Mutant Gliomas: Results From the VE-BASKET Study.|
|Journal||Journal of clinical oncology : official journal of the American Society of Clinical Oncology|
|Date||2018 Oct 23|
|Abstract Text||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.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.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.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.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|BRAF V600E||malignant glioma||predicted - sensitive||Vemurafenib||Phase II||Actionable||In a Phase II clinical trial (VE-BASKET), treatment of patients with gliomas harboring BRAF V600E mutations with Zelboraf (vemurafenib) resulted in a 25% (6/24) objective response rate, 5.5-month median progression free survival, 28.2 month median overall survival, and best overall response rates of 4.2% (1/24) for complete response, 20.8% (5/24) for partial response, and 41.7% (10/24) for stable disease (PMID: 30351999; NCT01524978).||30351999|
|BRAF V600E||pleomorphic xanthoastrocytoma||predicted - sensitive||Vemurafenib||Phase II||Actionable||In a Phase II clinical trial (VE-BASKET), Zelboraf (vemurafenib) treatment of BRAF V600E mutant pleomorphic xanthoastrocytomas resulted in a 42.9% (3/7) objective response rate, a 5.7-month median progression-free survival, and best overall response rates of 14.3% (1/7) for complete response, 28.6% (2/7) for partial response, and 42.9% (3/7) for stable disease (PMID: 30351999; NCT01524978).||30351999|