TAFINLAR is indicated, in combination with trametinib, for:...the treatment of pediatric patients 1 year of age and older with low-grade glioma (LGG) with a BRAF V600E mutation who require systemic therapy.

MEKINIST is indicated, in combination with dabrafenib, for:...the treatment of pediatric patients 1 year of age and older with low-grade glioma (LGG) with a BRAF V600E mutation who require systemic therapy…

Novartis announced today that the National Institute for Health and Care Excellence has published its Final Draft Guidance (FDG) recommending the combination therapy of dabrafenib with trametinib, within its marketing authorisation, as an option for treating low-grade glioma (LGG) with a BRAF V600E mutation in children and young people aged 1 year and over who require systemic treatment. The combination was also recommended for the treatment of high-grade glioma (HGG) with a BRAF V600E mutation in children and young people aged 1 year and over after at least 1 radiation or chemotherapy treatment.

Here we present final efficacy and safety results of a phase 2 basket trial of dabrafenib (BRAF kinase inhibitor) plus trametinib (MEK inhibitor) in eight cohorts of patients with BRAFV600E-mutated advanced rare cancers: anaplastic thyroid carcinoma (n = 36), biliary tract cancer (n = 43), gastrointestinal stromal tumor (n = 1), adenocarcinoma of the small intestine (n = 3), low-grade glioma (n = 13), high-grade glioma (n = 45), hairy cell leukemia (n = 55) and multiple myeloma (n = 19)...The primary endpoint of investigator-assessed overall response rate in these cohorts was 56%, 53%...The encouraging tumor-agnostic activity of dabrafenib plus trametinib suggests that this could be a promising treatment approach for some patients with BRAFV600E-mutated advanced rare cancers.

In the high-grade glioma cohort, median follow-up was 12·7 months (IQR 5·4–32·3) and 15 (33%; 95% CI 20–49) of 45 patients had an objective response by investigator assessment, including three complete responses and 12 partial responses. In the low-grade glioma cohort, median follow-up was 32·2 months (IQR 25·1–47·8). Nine (69%; 95% CI 39–91) of 13 patients had an objective response by investigator assessment, including one complete response, six partial responses, and two minor responses....Dabrafenib plus trametinib showed clinically meaningful activity in patients with BRAFV600E mutation-positive recurrent or refractory high-grade glioma and low-grade glioma, with a safety profile consistent with that in other indications.

Dabrafenib + trametinib demonstrated promising efficacy in pts with BRAF V600E mutation-positive recurrent/refractory HGG and LGG.