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. 2022 Apr 1;24(4):528-540.
doi: 10.1093/neuonc/noab247.

Prevalence of BRAFV600 in glioma and use of BRAF Inhibitors in patients with BRAFV600 mutation-positive glioma: systematic review

Lily J Andrews  1   2   3 , Zak A Thornton  1   2   3 , Saanwalshah S Saincher  1   2 , Ian Y Yao  1   2 , Sarah Dawson  2 , Luke A McGuinness  1   2 , Hayley E Jones  2 , Sarah Jefferies  4 , Susan C Short  5 , Hung-Yuan Cheng  2 , Alexandra McAleenan  1   2   3 , Julian P T Higgins  1   2 , Kathreena M Kurian  1   2   3   6
Affiliations

Prevalence of BRAFV600 in glioma and use of BRAF Inhibitors in patients with BRAFV600 mutation-positive glioma: systematic review

Lily J Andrews et al. Neuro Oncol. .

Abstract

Background: Detailed prevalence estimates of BRAFV600 mutations and BRAF inhibitor (BRAFi) treatment responses in V600-mutant glioma will inform trial development.

Methods: Our systematic review analyzed overall prevalence of BRAFV600 mutations in glioma and BRAFi treatment response.

Results: Based on 13 682 patients in 182 publications, the prevalence of BRAFV600 in epithelioid glioblastoma (eGBM) was 69% [95% CI: 45-89%]; pleomorphic xanthoastrocytoma (PXA): 56% [48-64%] anaplastic pleomorphic xanthoastrocytoma (aPXA): 38% [23-54%], ganglioglioma (GG): 40% [33-46%], and anaplastic ganglioglioma (aGG): 46% [18-76%]. Prevalence in astroblastoma was 24% [8-43%], desmoplastic infantile astrocytoma (DIA): 16% [0-57%], subependymal giant cell astrocytoma (SEGA): 8% [0-37%], dysembryoplastic neuroepithelial tumor (DNET): 3% [0-11%], diffuse astrocytoma (DA): 3% [0-9%], and pilocytic astrocytoma (PA): 3% [2-5%]. We reviewed 394 V600-mutant gliomas treated with BRAFi from 130 publications. One hundred and twenty-nine pediatric low-grade gliomas showed 4 (3.1%) complete response (CR); 53 (41.1%) partial response (PR); 64 (49.6%) stable disease (SD) and 8 (6.2%) progressive disease (PD). 25 pediatric high-grade gliomas showed CR; PR; SD; PD in 4 (16.0%); 10 (40.0%), 4 (16.0%); and 7 (28.0%) respectively. Thirty-nine adult low-grade gliomas showed CR; PR; SD; PD of 4 (10.3%); 17 (43.6%); 16 (41.0%) and 2 (5.1%) respectively. Ninety-seven adult high-grade gliomas showed CR; PR; SD; PD of 6 (6.2%); 31 (32.0%); 27 (27.8%); and 33 (34.0%) respectively.

Conclusions: BRAFV600 prevalence is highest in eGBM, PXA, aPXA, GG, aGG, and lower in astroblastoma, DIA, SEGA, DNET, DA, and PA. Our data provide the rationale for adjuvant clinical trials of BRAFi in V600-mutant glioma.

Keywords: BRAF; BRAF inhibitors; glioma; prevalence; systematic review.

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Figures

Fig. 1
Fig. 1
Summary forest plot displaying estimated BRAFV600 prevalence in glioma entities.
Fig. 2
Fig. 2
Kaplan-Meier survival curves showing PFS of the cohort, split by age and tumor grade.
Fig. 3
Fig. 3
Kaplan-Meier survival curves showing OS of the cohort, split by age and tumor grade.
Fig. 4
Fig. 4
Waterfall plot showing individual patient data for treatment for ganglioglioma. KEY: → (ongoing treatment), ✱ (overall survival), ■ (progression free survival), ♦ (time to best response), △ (drug dosage increase), ▽ (drug dosage decrease).
Fig. 5
Fig. 5
Waterfall plot showing individual patient data for treatment of pleomorphic xanthoastrocytoma. KEY: → (ongoing treatment), ✱ (overall survival), ■ (progression free survival), ♦ (time to best response).
Fig. 6
Fig. 6
Waterfall plot showing individual patient data for treatment for epithelioid glioblastoma. KEY: → (ongoing treatment), ✱ (overall survival), ■ (progression free survival), ♦ (time to best response), ▽ (drug dosage decrease).
See this image and copyright information in PMC

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