Durable Progression-Free Survival With the Use of BRAF and MEK Inhibitors in Four Cases With BRAF V600E-Mutated Gliomas. (1st September 2021)

• Record Type: Journal Article
• Authors: Fusco, Michael J.; Piña, Yolanda; Macaulay, Robert J.; Sahebjam, Solmaz; Forsyth, Peter A.; Peguero, Edwin; Walko, Christine M.
• Is Part Of: Cancer control. Volume 28(2021)
• Publication Date: 2021-09-01
• Subjects: glioblastoma -- BRAF -- CNS tumor -- brain tumor -- cancer -- treatment; Cancer -- Prevention -- Periodicals; Cancer -- Diagnosis -- Periodicals; Cancer -- Treatment -- Periodicals; Cancer -- Palliative treatment -- Periodicals; Cancer -- Prevention; Medical Oncology; Neoplasms -- prevention & control; Neoplasms -- therapy; Electronic journals; Periodicals; Periodicals; 616.994005
• DOI: 10.1177/10732748211040013
• Languages: English
• ISSNs: 1073-2748

Abstract

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.