Vemurafenib in pediatric patients with BRAFV600E mutated high-grade gliomas

Francisco Bautista; Angelo Paci; Veronique Minard-Colin; Christelle Dufour; Jacques Grill; Ludovic Lacroix; Pascale Varlet; Dominique Valteau-Couanet; Birgit Geoerger

doi:10.1002/pbc.24891

Vemurafenib in pediatric patients with BRAFV600E mutated high-grade gliomas

Pediatr Blood Cancer. 2014 Jun;61(6):1101-3. doi: 10.1002/pbc.24891. Epub 2013 Dec 3.

Authors

Francisco Bautista¹, Angelo Paci, Veronique Minard-Colin, Christelle Dufour, Jacques Grill, Ludovic Lacroix, Pascale Varlet, Dominique Valteau-Couanet, Birgit Geoerger

Affiliation

¹ Pediatric and Adolescent Oncology Department, Gustave Roussy, Villejuif, France.

PMID: 24375920
DOI: 10.1002/pbc.24891

Abstract

We present three pediatric patients with BRAFV600E mutant high-grade gliomas treated by vemurafenib on a nominative authorization level at our institution. One patient with anaplastic ganglioglioma experienced confirmed partial tumor response and significant clinical improvement and she is alive 20 months after start of treatment. A second patient with ganglioglioma responded transiently to re-introduction of vemurafenib after immunotherapy. Pharmacokinetic studies suggest that maximum concentration and exposure of vemurafenib at steady-state is dose-dependent and similar in children to that reported in adults. These cases suggest that BRAFV600 is an oncogenic driver in pediatric gliomas. Further exploration in clinical studies is ongoing.

Keywords: BRAF mutations; anaplastic ganglioglioma; pediatric brain tumors; pharmacokinetics; vemurafenib.

Publication types

Case Reports

MeSH terms

Antibodies, Monoclonal, Humanized / administration & dosage
Antineoplastic Agents / adverse effects
Antineoplastic Agents / pharmacokinetics
Antineoplastic Agents / therapeutic use*
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Astrocytoma / drug therapy*
Astrocytoma / enzymology
Bevacizumab
Brain Neoplasms / drug therapy*
Brain Neoplasms / enzymology
Camptothecin / administration & dosage
Camptothecin / analogs & derivatives
Cancer Vaccines / therapeutic use
Child
Combined Modality Therapy
Cranial Irradiation
Dacarbazine / administration & dosage
Dacarbazine / analogs & derivatives
Doxorubicin / administration & dosage
Doxorubicin / analogs & derivatives
Drug Evaluation
Fatal Outcome
Ganglioglioma / drug therapy*
Ganglioglioma / enzymology
Ganglioglioma / radiotherapy
Ganglioglioma / surgery
Humans
Immunotherapy
Indoles / adverse effects
Indoles / pharmacokinetics
Indoles / therapeutic use*
Infant
Irinotecan
Male
Mutation, Missense*
Neoplasm Proteins / antagonists & inhibitors*
Neoplasm Proteins / genetics
Neoplasm Proteins / physiology
Point Mutation*
Polyethylene Glycols / administration & dosage
Protein Kinase Inhibitors / adverse effects
Protein Kinase Inhibitors / pharmacokinetics
Protein Kinase Inhibitors / therapeutic use*
Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
Proto-Oncogene Proteins B-raf / genetics
Proto-Oncogene Proteins B-raf / physiology
Salvage Therapy
Sulfonamides / adverse effects
Sulfonamides / pharmacokinetics
Sulfonamides / therapeutic use*
Temozolomide
Thalamus
Treatment Outcome
Vemurafenib

Substances

Antibodies, Monoclonal, Humanized
Antineoplastic Agents
Cancer Vaccines
Indoles
Neoplasm Proteins
Protein Kinase Inhibitors
Sulfonamides
liposomal doxorubicin
Vemurafenib
Bevacizumab
Polyethylene Glycols
Irinotecan
Dacarbazine
Doxorubicin
BRAF protein, human
Proto-Oncogene Proteins B-raf
Camptothecin
Temozolomide