Dramatic Response of BRAF V600E Mutant Papillary Craniopharyngioma to Targeted Therapy.

Abstract

We recently reported that BRAF V600E is the principal oncogenic driver of papillary craniopharyngioma, a highly morbid intracranial tumor commonly refractory to treatment. Here, we describe our treatment of a man age 39 years with multiply recurrent BRAF V600E craniopharyngioma using dabrafenib (150mg, orally twice daily) and trametinib (2mg, orally twice daily). After 35 days of treatment, tumor volume was reduced by 85%. Mutations that commonly mediate resistance to MAPK pathway inhibition were not detected in a post-treatment sample by whole exome sequencing. A blood-based BRAF V600E assay detected circulating BRAF V600E in the patient's blood. Re-evaluation of the existing management paradigms for craniopharyngioma is warranted, as patient morbidity might be reduced by noninvasive mutation testing and neoadjuvant-targeted treatment.

• Authors: Priscilla K Brastianos, Ganesh M Shankar, Corey M Gill, Amaro Taylor-Weiner, Naema Nayyar, David J Panka, Ryan J Sullivan, Dennie T Frederick, Malak Abedalthagafi, Pamela S Jones, Ian F Dunn, Brian V Nahed, Javier M Romero, David N Louis, Gad Getz, Daniel P Cahill, Sandro Santagata, William T Curry Jr, Fred G Barker 2nd
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 108 Issue 2 (Feb 2016) ISSN: 1460-2105 [Electronic] United States
• PMID: 26498373 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: [email protected].

Chemical References

• Imidazoles
• Oximes
• Protein Kinase Inhibitors
• Pyridones
• Pyrimidinones
• trametinib
• Glutamic Acid
• BRAF protein, human
• Proto-Oncogene Proteins B-raf
• Valine
• dabrafenib

Topics

• Adult
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Craniopharyngioma (drug therapy, genetics, pathology, surgery)
• Craniotomy
• Cytoreduction Surgical Procedures
• Drug Administration Schedule
• Glutamic Acid
• Humans
• Imidazoles (administration & dosage)
• Magnetic Resonance Imaging
• Male
• Molecular Targeted Therapy (methods)
• Mutation
• Neoplasm Recurrence, Local (drug therapy, genetics)
• Neoplasm, Residual (surgery)
• Oximes (administration & dosage)
• Pituitary Neoplasms (drug therapy, genetics, pathology, surgery)
• Protein Kinase Inhibitors (administration & dosage)
• Proto-Oncogene Proteins B-raf (antagonists & inhibitors, genetics)
• Pyridones (administration & dosage)
• Pyrimidinones (administration & dosage)
• Treatment Outcome
• Valine