In a phase 2 trial of 110 pediatric patients with low-grade glioma with BRAF V600 mutations, the combination of dabrafenib plus trametinib had significantly more responses, longer progression-free survival, and a better safety profile than the standard chemotherapy approach of carboplatin plus vincristine, researchers report. “Dabrafenib is a selective inhibitor targeting BRAF V600 mutations, and trametinib is a MEK1–2 inhibitor,” the authors write. “Overall, these findings show the value of early molecular testing in children with low-grade glioma to determine the presence or absence of BRAF V600 mutations.”
Patients with pediatric low-grade glioma with BRAF V600 mutations who were to receive first-line therapy were randomized to dabrafenib plus trametinib or carboplatin plus vincristine. Based on the independently assessed complete or partial response, the clinical benefit (complete or partial response or stable disease for ≥24 weeks), and progression-free survival, the investigators found: “At a median follow-up of 18.9 months, an overall response occurred in 47% of the patients treated with dabrafenib plus trametinib and in 11% of those treated with chemotherapy (risk ratio, 4.31; 95% confidence interval [CI], 1.7 to 11.2; P <0.001). Clinical benefit was observed in 86% of the patients receiving dabrafenib plus trametinib and in 46% receiving chemotherapy (risk ratio, 1.88; 95% CI, 1.3 to 2.7). The median progression-free survival was significantly longer with dabrafenib plus trametinib than with chemotherapy (20.1 months vs. 7.4 months; hazard ratio, 0.31; 95% CI, 0.17 to 0.55; P <0.001). Grade 3 or higher adverse events occurred in 47% of the patients receiving dabrafenib plus trametinib and in 94% of those receiving chemotherapy.”