Vemurafenib in patients with BRAFV600 mutant glioma: A cohort of the histology-independent VE-basket study.

Abstract

2004 Background: Recurrent malignant gliomas (MG) are a universally fatal disease in desperate need of better therapies. Pleiomorphic xanthoastrocytomas (PXA) and juvenile pilocytic astrocytomas (JPA) typically have better outcomes, although when recurrent, also represent an aggressive disease with no proven effective chemotherapy. BRAFV600 alterations have been identified in a substantial proportion of gliomas, including glioblastoma (GBM), astrocytoma, PXA, and JPA. The phase 2, open-label, histology-independent VE-BASKET study of vemurafenib, a selective BRAFV600 kinase inhibitor, in patients with BRAF mutation-positive non-melanoma tumors, included those with gliomas in the ‘all-others’ cohort. We now report final data for patients with recurrent gliomas. Methods: Patients received vemurafenib (960 mg bid) until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed response rate; secondary endpoints included clinical benefit rate (confirmed complete or partial response or stable disease lasting ≥6 months), progression-free survival (PFS), overall survival (OS), and toxicity. ClinicalTrials.gov NCT01524978. Results: 24 patients (median age 32 years; 18 female, 6 male) with glioma were treated, including mg (n = 11; 6 GBM and 5 anaplastic astrocytoma [AA]), PXA (n = 7), anaplastic ganglioglioma (AG, n = 3), JPA (n = 2), and unknown (n = 1). In patients with mg (n = 11), best response included PR (n = 1; AA), SD (n = 5), PD (n = 3), and unknown (n = 2). Two patients with mg had durable SD lasting 12.9 months (GBM) and 14.9 months (AA). In patients with PXA (n = 7), best response included CR (n = 1), PR (n = 2), SD (n = 3), and PD (n = 1). Additionally, 1 patient with JPA and 1 with AG achieved a PR. The most frequent AEs included arthralgia (67%), melanocytic nevus (38%), palmar-plantar erythrodysesthesia (38%), photosensitivity reaction (38%) and alopecia (33%). Conclusions: Vemurafenib demonstrated activity in patients with BRAFV600 mutant glioma. The safety profile was similar to that seen in previous melanoma studies. Survival data will be presented. Clinical trial information: NCT01524978.