title: Vemurafenib in pediatric patients with BRAFV600E mutated high-grade gliomas.
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.
authors.affiliation: Pediatric and Adolescent Oncology Department, Gustave Roussy, Villejuif, France.
authors.forename: Francisco
authors.initials: F
authors.lastname: Bautista
authors.forename: Angelo
authors.initials: A
authors.lastname: Paci
authors.forename: Veronique
authors.initials: V
authors.lastname: Minard-Colin
authors.forename: Christelle
authors.initials: C
authors.lastname: Dufour
authors.forename: Jacques
authors.initials: J
authors.lastname: Grill
authors.forename: Ludovic
authors.initials: L
authors.lastname: Lacroix
authors.forename: Pascale
authors.initials: P
authors.lastname: Varlet
authors.forename: Dominique
authors.initials: D
authors.lastname: Valteau-Couanet
authors.forename: Birgit
authors.initials: B
authors.lastname: Geoerger
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001254:Astrocytoma / Q000188:drug therapy* / Q000201:enzymology; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D019496:Cancer Vaccines / Q000627:therapeutic use; D002648:Child; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D004341:Drug Evaluation; D017809:Fatal Outcome; D018303:Ganglioglioma / Q000188:drug therapy* / Q000201:enzymology / Q000532:radiotherapy / Q000601:surgery; D006801:Humans; D007167:Immunotherapy; D007211:Indoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007223:Infant; D000077146:Irinotecan; D008297:Male; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D017354:Point Mutation; D011092:Polyethylene Glycols / Q000008:administration & dosage; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D016879:Salvage Therapy; D013449:Sulfonamides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077204:Temozolomide; D013788:Thalamus; D016896:Treatment Outcome; D000077484:Vemurafenib
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D007211:Indoles; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; C506643:liposomal doxorubicin; D000077484:Vemurafenib; D000068258:Bevacizumab; D011092:Polyethylene Glycols; D000077146:Irinotecan; D003606:Dacarbazine; D004317:Doxorubicin; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D002166:Camptothecin; D000077204:Temozolomide
keywords: BRAF mutations; anaplastic ganglioglioma; pediatric brain tumors; pharmacokinetics; vemurafenib