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Top Line: Do recurrent BRAF mutated gliomas respond to BRAF targeted therapy?

The Study: A subset of low-grade (~10%) and high-grade gliomas (<5%) have BRAF V600E mutations, and these typically occur in IDH wild type tumors. ROAR is a single-arm phase 2 basket trial of patients with recurrent or progressive BRAF V600E mutated low and high grade glioma. There were 45 high grade gliomas (including 31 GBMs) and 13 low grade gliomas. Patients were treated with the dabrafenib (a BRAF inhibitor) and trametinib (a MEK inhibitor) to provide dual blockade of the constitutively activated MAPK pathway. Among those with HGG, the response rate (complete and partial) was 33%. Among those with LGG, the response rate (complete, partial, and minor) was 69%. Median PFS was 3.8 months and median OS was 17.6 months among those with HGG, while median PFS and OS were not reached among those with LGG. With these results, we may see BRAF targeted therapy as a future option for some recurrent and refractory gliomas. However, more trials are needed to know 1) if dual MAPK inhibition is as good as other therapies for progressive glioma or 2) if dual MAPK inhibition could be used in earlier lines of therapy.

TBL: Two-thirds of low grade and one-third of high grade recurrent/progressive BRAF-mutated gliomas respond to combination dabrafenib and trametinib. | Wen, Lancet Oncol 2021

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