Activity of Vemurafenib in BRAF V600–Mutant Gliomas


Key Points

  • The overall response rate was 25%.
  • Responses appeared to be better among patients with malignant diffuse glioma or pleomorphic xanthoastrocytoma.

In a multicohort study (VE-BASKET study) in patients with BRAF V600–mutant nonmelanoma cancers in the Journal of Clinical Oncology, Kaley et al found evidence of activity of vemurafenib (Zelboraf) in gliomas that appeared to vary by glioma subtype.  

Study Details

In the study, 24 patients were treated with vemurafenib 960 mg twice daily until disease progression, withdrawal, or unacceptable toxicity. Patients had a median age of 32 years and 18 were women; 11 had malignant diffuse glioma (6 with glioblastoma, 5 with anaplastic astrocytoma), 7 had pleomorphic xanthoastrocytoma (PXA), 3 had anaplastic ganglioglioma, 2 had pilocytic astrocytoma, and 1 had high-grade glioma not otherwise specified. Overall, 75% of patients had received ≥ 1 prior systemic therapy. Response was assessed by RECIST v1.1.

Treatment Outcomes

The confirmed objective response rate was 25% (95% confidence interval [CI] = 10%–47%) and clinical benefit rate was 38%. Among the 11 patients with malignant diffuse glioma, there was 1 partial response (in a patient with anaplastic astrocytoma) and 5 patients (3 with glioblastoma, 2 with anaplastic astrocytoma) had stable disease, with 2 having stable disease for > 1 year. Among the 7 patients with PXA, 1 had complete response, 2 had partial response, and 3 had stable disease. Partial responses were observed in 1 patient with pilocytic astrocytoma and 1 with anaplastic ganglioglioma. The complete response lasted ≥ 25.9 months and the partial responses lasted 13.1, 9.9, 7.5, 3.4, and 2.4 months. Median progression-free survival for all patients was 5.5 months. Median overall survival for all patients was 28.2 months. The safety profile of vemurafenib was generally consistent with that in other previously published studies.

The investigators concluded, “Vemurafenib demonstrated evidence of durable antitumor activity in some patients with BRAF V600–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.”

The study was funded by F. Hoffmann-La Roche and supported by grants from the National Institutes of Health.

David M. Hyman, MD, of Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

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