The New England Journal of MedicineDabrafenib plus Trametinib in Pediatric Glioma with BRAF V600 Mutations

The combination therapy shines in a Phase 2 trial

In a quest to optimize treatment for pediatric low-grade glioma patients with BRAF V600 mutations, a phase 2 clinical trial offers compelling evidence that dabrafenib in combination with trametinib outperforms standard chemotherapy in terms of response rate, progression-free survival, and safety profile.

HCN Medical Memo
This study underscores the potential of using dabrafenib plus trametinib as an effective and safer first-line therapy compared to standard chemotherapy. This combination therapy demonstrates a notably higher response rate and extended progression-free survival, positioning it as a new standard of care that could reshape clinical decision-making.

Study Design

• Phase 2 clinical trial involving pediatric patients with low-grade glioma and BRAF V600 mutations.
• 110 patients were randomly assigned in a 2:1 ratio: 73 to receive dabrafenib plus trametinib, and 37 to receive standard chemotherapy (carboplatin plus vincristine).
• Primary outcome measured was the independently assessed overall response, along with clinical benefit and progression-free survival.

Pediatric low-grade gliomas constitute up to 30% of all childhood central nervous system tumors.

Key Findings

• Overall response in the dabrafenib plus trametinib group was 47%, compared to 11% in the standard chemotherapy group (Risk ratio, 4.31; P<0.001).
• Clinical benefit was noted in 86% of the patients on dabrafenib plus trametinib vs. 46% on standard chemotherapy (Risk ratio, 1.88).
• Median progression-free survival was significantly longer in the combination therapy group: 20.1 months vs. 7.4 months (Hazard ratio, 0.31; P<0.001).
• Grade 3 or higher adverse events were noted in 47% of the patients on combination therapy and 94% on chemotherapy.

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