Related Experiment Video
Updated: Oct 17, 2025
A Melanoma Patient-Derived Xenograft Model
Published on: May 20, 2019
Durable Progression-Free Survival With the Use of BRAF and MEK Inhibitors in Four Cases With BRAF V600E-Mutated
Michael J Fusco1, Yolanda Piña2, Robert J Macaulay2,3
1Department of Individualized Cancer Medicine, 25301Moffitt Cancer Center, Tampa, FL, USA.
Introduction:
BRAF V600 E mutations have been identified in a subset of patients with primary brain tumors. Combination therapy with BRAF and Mitogen-activated protein kinase (MEK) inhibitors (BRAF/MEKi) targeting sequential steps in the MAPK pathway has replaced BRAFi monotherapy as the standard of care in multiple tumors with BRAF V600 E mutations, and clinical evidence for this strategy continues to grow in primary brain tumors.
Case Series:
We describe four patients with BRAF V600 E mutated gliomas, including a 21-year-old woman with a ganglioglioma WHO grade I, a 19-year-old man with a pleomorphic xanthoastrocytoma WHO grade III, and 21-year-old and 33-year-old women with epithelioid GBM WHO grade IV, who achieved durable progression-free survival with combination BRAF/MEKi.
Conclusion:
Combination of BRAF/MEK inhibition can be a novel, promising approach as targeted therapy in gliomas with BRAF V600 E mutations, especially those that are resistant to standard therapy. Our cases, along with other early reports utilizing dabrafenib/trametinib, highlight the importance of somatic next-generation sequencing, particularly in younger patients. Interim results from clinical trials utilizing dabrafenib/trametinib have been promising thus far, and our case series suggests that durable clinical benefit is possible, even in the setting of glioblastoma, WHO grade IV.
Insights
Combination BRAF/MEK inhibitors show promise for BRAF V600E mutated gliomas, offering durable progression-free survival. This targeted therapy is particularly effective in tumors resistant to standard treatments.
Area of Science:
- Neuro-oncology
- Molecular targeted therapy
- Genomic medicine
Background:
- BRAF V600E mutations are found in a subset of primary brain tumors.
- Combination BRAF/MEK inhibitors (BRAF/MEKi) are now standard for BRAF V600E-mutated tumors, with growing evidence in brain tumors.
Observation:
- Four patients with BRAF V600E-mutated gliomas (ganglioglioma WHO grade I, pleomorphic xanthoastrocytoma WHO grade III, and two epithelioid glioblastoma WHO grade IV) received combination BRAF/MEKi.
- All four patients achieved durable progression-free survival.
Findings:
- Combination BRAF/MEKi therapy demonstrated efficacy in BRAF V600E-mutated gliomas.
- Durable clinical benefit was observed, including in glioblastoma WHO grade IV.
Implications:
- BRAF/MEK inhibition represents a novel, promising targeted therapy for BRAF V600E-mutated gliomas, especially treatment-resistant cases.
- Somatic next-generation sequencing is crucial for identifying eligible patients, particularly younger individuals.
- Early clinical trial results and case series suggest the potential for long-term patient benefit.
