BRAF V600E-Mutant Glioblastoma with Extracranial Metastases Responsive to Combined BRAF and MEK Targeted Inhibition: A Case Report

Vasu Munjapara; Thatcher Heumann; Karisa C Schreck; John M Gross; Carlos Perez-Heydrich; Sachin K Gujar; Charles G Eberhart; Matthias Holdhoff

doi:10.1159/000525660

BRAF V600E-Mutant Glioblastoma with Extracranial Metastases Responsive to Combined BRAF and MEK Targeted Inhibition: A Case Report

Case Rep Oncol. 2022 Oct 7;15(3):909-917. doi: 10.1159/000525660. eCollection 2022 Sep-Dec.

Authors

Vasu Munjapara¹, Thatcher Heumann¹, Karisa C Schreck^{1

2}, John M Gross³, Carlos Perez-Heydrich¹, Sachin K Gujar⁴, Charles G Eberhart³, Matthias Holdhoff^{1

2}

Affiliations

¹ aDepartment of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
² bDepartment of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
³ cDepartment of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁴ dDepartment of Radiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Abstract

Recent advancements in understanding the biology of glioblastomas (GBM) and increasing adoption of genomic sequencing in oncology practice have led to the discovery of several targetable mutations in these cancers. Among them, the BRAF V600E mutation can be found in approximately 3% of GBM. Despite the aggressive nature of GBM, metastatic disease is rarely observed. While there are growing data utilizing BRAF-targeting strategies in patients with GBM, data examining their efficacy in cases of metastatic GBM are lacking. We present the case of a 46-year-old female with GBM, isocitrate dehydrogenase (IDH)-wildtype and O⁶-methylguanine-DNA methyltransferase promoter (MGMT) unmethylated, BRAF V600E-mutant, and MYC amplified with extra-central nervous system spread to the spine and lung. Four months after completion of treatment with standard chemoradiation and temozolomide, the patient developed severe back pain, leading to the eventual discovery of her metastatic disease. Based on the presence of the BRAF V600E mutation, the patient was treated with and achieved an intracranial and systemic response to combination BRAF-MEK targeted inhibition for 9 months before evidence of progression.

Keywords: Actionable mutation; BRAF V600E-mutant; Glioblastoma; Metastatic; Targeted therapy.

Publication types

Case Reports

Grants and funding

This work was supported by the Sidney Kimmel Comprehensive Cancer Center Core Grant P30CA006973. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.