Response of recurrent BRAFV600E mutated ganglioglioma to Vemurafenib as single agent

Abstract

BackgroundGanglioglioma (GG) and pilocytic astrocytoma (PA) represent the most frequent low-grade gliomas (LGG) occurring in paediatric age. LGGs not amenable of complete resection (CR) represent a challenging subgroup where traditional treatments often fail. Activation of the MAP Kinase (MAPK) pathway caused by the BRAFV600E mutation or the KIAA1549-BRAF fusion has been reported in pediatric GG and PA, respectively.Case presentationWe report on a case of BRAFV600E mutated cervicomedullary GG treated with standard chemotherapy and surgery. After multiple relapse, BRAF status was analyzed by immunohistochemistry and sequencing showing a BRAFV600E mutation. Treatment with Vemurafenib as single agent was started. For the first time, a radiological and clinical response was obtained after 3 months of treatment and sustained after 6 months.ConclusionOur experience underline the importance of understanding the driver molecular alterations of LGG and suggests a role for Vemurafenib in the treatment of pediatric GG not amenable of complete surgical resection.

Successful Retreatment of a Child with a Refractory Brainstem Ganglioglioma with Vemurafenib

“…In contrast, we document successful sustained objective response and re‐response to single agent vemurafenib for 1 year and for 9 months and ongoing, respectively. Similar to our report, an infant with recurrent cervicomedullary GG was treated with vemurafenib as a single agent and demonstrated a sustained response at a follow up of only 6 months . The responses of two additional patients with anaplastic GGs treated with vemurafenib also have been reported .…”

“…BRAF inhibitors offer an alternative treatment approach for refractory BRAFV600E positive (+) BS GGs. Although there are two previous case reports of objective tumor response to Vemurafenib in pediatric BRAFV600E (+) BS GG, only one utilized vemurafenib as a single agent, and the reported follow‐up time on treatment in each case was short (3–6 months) . In pediatric BS GG, information regarding the potential duration of response and clinical course during and after the discontinuation of long‐term administration of vemurafenib is lacking.…”

Past and future challenges for the clinical care of children with low-grade gliomas

“…There are now several BRAFV600E specific inhibitors in clinic and individual case reports are encouraging regarding the clinical activity in BRAFV600 mutated gliomas (15)(16)(17). The PNOC is currently conducting a phase I clinical trial of specific BRAFV600E inhibitor vemurafenib in children with BRAFV600E mutated gliomas.…”

Input of molecular analysis in medical management of primary brain tumor patients

“…Pilocytic astrocytomas exhibiting genetic abnormalities disrupting MAPK are candidate diseases for these molecular targeted therapies. Interestingly, it has been shown that pilomyxoid astrocytoma, ganglioglioma and pleomorphic xanthoastrocytoma, which are other subtypes of gliomas with frequent MAPK signaling pathway activation, can respond to vemurafenib [45][46][47].…”