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PMID (31217909)
Authors Woo PYM, Lam TC, Pu JKS, Li LF, Leung RCY, Ho JMK, Zhung JTF, Wong B, Chan TSK, Loong HHF, Ng HK
Title Regression of BRAFV600E mutant adult glioblastoma after primary combined BRAF-MEK inhibitor targeted therapy: a report of two cases.
Journal Oncotarget
Vol 10
Issue 38
Date 2019 Jun 04
URL
Abstract Text Up to 15% of young adults with glioblastoma have the activating oncogenic BRAFV600E mutation, an actionable target of the MAPK signal transduction pathway governing tumor cell proliferation. Small molecule inhibitors of BRAF and MEK, a downstream protein immediately following BRAF, have been shown to confer a survival advantage for patients with BRAFV600E mutant advanced melanoma. We describe our experience using this combined target therapy for two patients with BRAFV600E mutant glioblastoma (GBM) as primary treatment due to extenuating clinical circumstances that prohibited the prescription of standard treatment.The two patients were both 22 years old on presentation. After the initial tumor resection, they both developed rapid deterioration in performance status within a few weeks due to leptomeningeal metastases. In view of the critical condition, BRAF and MEK inhibitors were prescribed as first line treatment. The two patients both achieved dramatic clinical response, which was parallel to the impressive radiological regression of the disease. Unfortunately, the duration of disease control was short as drug resistance developed rapidly. The two patients died 7 and 7.5 month after initial diagnosis of GBM.Primary treatment with inhibitors of BRAF and MEK can lead to tumor regression for patients with BRAFV600E mutant glioblastoma. We therefore recommend that all young GBM patients should undergo BRAFV600E mutation testing, especially for those with unusual aggressive clinical course.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF V600E glioblastoma multiforme predicted - sensitive Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in significant clinical improvement in a patient with epithelioid glioblastoma harboring BRAF V600E, however, her disease progressed after 3 months of therapy (PMID: 31217909). 31217909
BRAF V600E glioblastoma multiforme predicted - sensitive Cobimetinib + Vemurafenib Case Reports/Case Series Actionable In a clinical case study, a patient with epithelioid glioblastoma harboring BRAF V600E continued to response as Cotellic (cobimetinib) was added to Zelboraf (vemurafenib) treatment (PMID: 31217909). 31217909
BRAF V600E glioblastoma multiforme predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a clinical case study, Zelboraf (vemurafenib) treatment resulted in tumor regression as confirmed by MRI after 3-weeks of treatment in a patient with epithelioid glioblastoma harboring BRAF V600E (PMID: 31217909). 31217909