Prolonged Response Induced by Single Agent Vemurafenib in a BRAF V600E Spinal Ganglioglioma: A Case Report and Review of the Literature

Abstract

Spinal ganglioglioma is a rare low-grade, slow-growing tumor of the central nervous system affecting mostly children and young adults. After surgery, some patients show tumor recurrence and/or malignant transformation. Gangliogliomas harbor molecular deficiencies such as mutations in the B-rapidly accelerated fibrosarcoma ( BRAF ) gene, resulting in activation of a downstream signaling pathway and cancer development. Vemurafenib is a BRAF inhibitor used to treat patients with BRAF V600E -mutated cancer. Although a few studies have reported the clinical responses in gangliogliomas, the sequence and duration of treatment have not been established. We describe a case of an adult with a progressive BRAF V600E mutant spinal cord ganglioglioma 9 years after surgery who was treated with vemurafenib. This treatment resulted in a partial response within 2 months, which was sustained for more than a year. The patient then decided to stop treatment because of side effects. Despite this decision, the tumor showed no sign of progression 21 months after treatment discontinuation. This is the first reported case of a response to vemurafenib in an adult with progressive spinal cord BRAF V600E -mutated ganglioglioma which was sustained after treatment discontinuation.

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].…”

Combination of BRAF and MEK inhibition in BRAF V600E mutant low‐grade ganglioglioma

“…Evidence from the phase 2 VE‐basket study supports the use of single‐agent BRAF inhibition in BRAF V600E mutant gliomas, which included three anaplastic gangliogliomas . Other case reports have reported the activity of the combination of BRAF and MEK inhibition in high‐grade gangliogliomas, and of single‐agent BRAF inhibition in low‐grade ganglioglioma . To our knowledge, there are no previously published reports of combined BRAF and MEK inhibition in low‐grade ganglioglioma.…”

Treatment of BRAF V600E mutated ganglioglioma of the third ventricle with dabrafenib

“…BRAF mutated GGs have been treated successfully with BRAF inhibitors, in multiple anatomic locations. [ 7 ] Garnier et al . reviewed 14 patients with GG treated with BRAF inhibitors.…”

“…The patient stopped treatment due to side effects, and the tumor did not show progression for 21 months after treatment discontinuation. [ 7 ] Further, a 21-year-old male with temporal lobe and posterior brainstem GG had gross total resection and vincristine, carboplatin, radiotherapy, temozolomide, irinotecan, and bevacizumab before starting BRAF inhibitor treatment. He experienced GG recurrence 11 years later and began dabrafenib and gemfibrozil.…”