Dramatic Response of BRAF V600E Mutant Papillary Craniopharyngioma to Targeted Therapy

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

doi:10.1093/jnci/djv310

Dramatic Response of BRAF V600E Mutant Papillary Craniopharyngioma to Targeted Therapy

J Natl Cancer Inst. 2015 Oct 23;108(2):djv310. doi: 10.1093/jnci/djv310. Print 2016 Feb.

Authors

Priscilla K Brastianos¹, Ganesh M Shankar¹, Corey M Gill¹, Amaro Taylor-Weiner¹, Naema Nayyar¹, David J Panka¹, Ryan J Sullivan¹, Dennie T Frederick¹, Malak Abedalthagafi¹, Pamela S Jones¹, Ian F Dunn¹, Brian V Nahed¹, Javier M Romero¹, David N Louis¹, Gad Getz¹, Daniel P Cahill¹, Sandro Santagata¹, William T Curry Jr¹, Fred G Barker 2nd¹

Affiliation

¹ Department of Medicine (PKB, RS), Department of Neurology (PKB, CMG), Department of Neurosurgery (GMS, PJ, BN, DPC, WTC, FGB), Department of Surgical Oncology (DTF), Department of Pathology (GG, DNL), Cancer Center (PKB, CMG, NN, DNL), Department of Radiology (JR) Massachusetts General Hospital, Harvard Medical School, Boston, MA; Broad Institute (ATW, GG), Department of Pathology, (MA, SS) and Department of Neurosurgery, Brigham and Women's Hospital (IFD), Boston, MA; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (DJP).

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.

Publication types

Case Reports
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Craniopharyngioma / drug therapy*
Craniopharyngioma / genetics*
Craniopharyngioma / pathology
Craniopharyngioma / 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*
Neoplasm Recurrence, Local / genetics
Neoplasm, Residual / surgery
Oximes / administration & dosage
Pituitary Neoplasms / drug therapy*
Pituitary Neoplasms / genetics*
Pituitary Neoplasms / pathology
Pituitary Neoplasms / surgery
Protein Kinase Inhibitors / administration & dosage
Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
Proto-Oncogene Proteins B-raf / genetics*
Pyridones / administration & dosage
Pyrimidinones / administration & dosage
Treatment Outcome
Valine

Substances

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

Grants and funding

2K12CA090354-11/CA/NCI NIH HHS/United States