Dabrafenib, trametinib combo shows promising results in pediatric low-grade glioma
The combination of dabrafenib and trametinib shows significantly more promising results in treating pediatric low-grade glioma with the BRAF V600E mutation compared to standard chemotherapy, according to results of a phase 2 clinical trial.
This combination therapy resulted in higher response rates, longer progression-free survival, and a more favorable safety profile.
The trial randomly assigned 110 patients slated for first-line therapy for pediatric low-grade glioma with BRAF V600 mutations, with 73 receiving dabrafenib plus trametinib and 37 undergoing standard chemotherapy (carboplatin plus vincristine). The primary endpoint, independently assessed overall response according to the Response Assessment in Neuro-Oncology criteria, revealed a 47% response rate in patients treated with dabrafenib plus trametinib, compared to 11% in those receiving chemotherapy.
The clinical benefit was observed in 86% of patients administered dabrafenib plus trametinib, while 46% experienced it in the chemotherapy group. The median progression-free survival demonstrated a significant extension with dabrafenib plus trametinib, standing at 20.1 months compared to 7.4 months with chemotherapy.
Grade 3 or higher adverse events occurred in 47% of patients on dabrafenib plus trametinib, as opposed to 94% in the chemotherapy arm.
Bouffet E, Hansford JR, Garrè ML, et al. Dabrafenib plus Trametinib in Pediatric Glioma with BRAF V600 Mutations. N Engl J Med. 2023;389(12):1108-1120. doi: 10.1056/NEJMoa2303815. PMID: 37733309.