A New Treatment for Childhood Brain Cancer 

A targeted therapy regimen was approved to treat some children with brain cancer 

The U.S. Food and Drug Administration (FDA) has approved dabrafenib (Tafinlar) in combination with trametinib (Mekinist) for pediatric patients 1 year of age or older who have low-grade glioma harboring a BRAF V600E mutation and who require systemic therapy. The FDA also approved new oral formulations of dabrafenib and trametinib for pediatric patients unable to swallow pills. 

Dabrafenib and trametinib are targeted therapies that block the cancer-promoting activity of the BRAF and MEK cell signaling proteins, respectively. Both BRAF and MEK contribute to a signaling pathway that is commonly activated in pediatric low-grade gliomas. By blocking both BRAF and MEK, the combination therapy can more effectively shut down the signaling pathway. A particular mutation in BRAF, known as V600E, promotes unregulated cell proliferation and is associated with poor response to chemotherapy and radiotherapy in patients with low-grade glioma.  

The dabrafenib and trametinib combination therapy was previously approved for individuals 6 years of age and older with BRAF V600E-mutated unresectable or metastatic solid tumors that had progressed following prior therapy. The latest approval marks the first systemic therapy approved for the first-line treatment of pediatric low-grade glioma with a BRAF V600E mutation. 

The approval is based on results from Study CDRB436G2201, a multicenter, open-label clinical trial that included 110 pediatric patients with BRAF V600E-mutated low-grade glioma who required systemic therapy. The patients were randomly assigned to receive dabrafenib in combination with trametinib or a chemotherapy regimen of carboplatin and vincristine.  

Patients in the dabrafenib and trametinib arm had a significantly higher rate of treatment response compared with those in the chemotherapy arm (46.6% vs. 10.8%, respectively). Patients treated with dabrafenib and trametinib also had a 69% lower risk of disease progression, with a progression-free survival of 20.1 months, as compared with 7.4 months among patients receiving chemotherapy.  

Low-grade glioma is the most common type of pediatric brain cancer. According to federal statistics, cancers of the brain and nervous system were diagnosed in 3.2 per 100,000 children each year between 2015 and 2019 in the U.S. The yearly death rate from these cancers was 0.6 per 100,000 children between 2016 and 2020. 

The FDA rendered its decision on March 16, 2023.