Access Program for Unapproved and Off-Label Drug Use in Pediatric BRAF V600E-Mutated Brain Tumors in Japan

Pediatr Blood Cancer. 2025 Mar;72(3):e31510. doi: 10.1002/pbc.31510. Epub 2025 Jan 6.

Abstract

Programs allowing access to investigational drugs and off-label drug use for serious diseases have often been applied to pediatric cancers. A clinical study conducted under the Japanese "Patient-Proposed Healthcare Services" evaluated the efficacy and safety of dabrafenib plus trametinib in children with BRAF V600 mutant glioma (jRCTs071210071). This study successfully provided unapproved and off-label medications to four enrolled patients, two with low-grade glioma and two with high-grade glioma (median age: 10.5 years), until regulatory approval. The timeframe and data collection from such access programs need to be optimized for pediatric patients in accordance with the healthcare system of each nation.

Keywords: BRAF V600E‐mutated glioma; access program; dabrafenib; patient‐proposed healthcare services; trametinib.

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / genetics
  • Child
  • Child, Preschool
  • Female
  • Glioma / drug therapy
  • Glioma / genetics
  • Humans
  • Imidazoles* / therapeutic use
  • Japan
  • Male
  • Mutation
  • Off-Label Use*
  • Oximes* / therapeutic use
  • Proto-Oncogene Proteins B-raf* / genetics
  • Pyridones* / therapeutic use
  • Pyrimidinones / administration & dosage
  • Pyrimidinones / therapeutic use

Substances

  • Proto-Oncogene Proteins B-raf
  • BRAF protein, human
  • dabrafenib
  • Pyridones
  • Oximes
  • Imidazoles
  • trametinib
  • Pyrimidinones