Dabrafenib, Trametinib Combination Receives FDA Approval for Pediatric Low-Grade Glioma with BRAF V600E Mutation

Liquid formulations of dabrafenib plus trametinib were also approved, marking the first time a BRAF/MEK inhibitor has been developed in a formulation suitable for patients as young as 1 year of age.

The FDA has approved dabrafenib (Tafinlar; Novartis) plus trametinib (Mekinist; Novartis) 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.

Liquid formulations of the drugs were also approved, marking the first time a BRAF/MEK inhibitor has been developed in a formulation suitable for patients as young as 1 year of age. The FDA action makes dabrafenib plus trametinib the first and only approved combination targeted therapy to treat pediatric patients with BRAF V600E LGG, which is the most common form of pediatric brain cancer.

“Pediatric cancer research is vital to uncover new treatment methods for a population,” said Eric Bouffet, MD, FRCPC, principal investigator of the TADPOLE clinical trial, in a press release. “Developing targeted therapies based on the unique genetic features of a patient’s tumor is the future of pediatric cancer care.”

Dabrafenib and trametinib are the worldwide targeted therapy leader in BRAF/MEK-inhibition research, according to the Novartis press release. The combination targeted therapy may help slow tumor growth by blocking signals associated with the BRAF and MEK kinases that are implicated in the growth of several cancer types. Thus far, it has been studied in more than 6000 BRAF-positive patients in more than 20 ongoing and completed trials, including in pediatric patients 1 year of age and older.

The approval is based on results from the phase 2/3 TADPOLE trial, which showed that patients randomized to receive dabrafenib and trametinib experienced a statistically significant improvement in overall response rate of 47%, versus 11% for those randomized to receive chemotherapy. At a median follow-up of 18.9 months, median progression-free survival was 20.1 months with the combination therapy compared to 7.4 months with chemotherapy.

“It is more important than ever to test for genetic mutations in patients living with low-grade glioma,” said Roger Packer, MD, senior vice president of the Center for Neurosciences and Behavioral Medicine at Children’s National Hospital, in the press release. “This FDA approval may offer new hope to pediatric patients living with BRAF V600E low-grade glioma. This has the potential to change the way health care providers treat these pediatric patients, offering a significant advancement compared to chemotherapy.”

The safety profile of dabrafenib and trametinib observed in the study was consistent with the known safety profile in other approved indications. The most common adverse effects (≥15%) were pyrexia (68%), rash (51%), headache (47%), vomiting (34%), musculoskeletal pain (34%), fatigue (33%), diarrhea (29%), dry skin (26%), nausea (25%), hemorrhage (25%), abdominal pain (25%), dermatitis acneiform (22%), dizziness (15%), upper respiratory tract infection (15%), and increased weight (15%).

“This new indication for Tafinlar and Mekinist is a potential new standard of care treatment option for young patients with this form of brain cancer with a BRAF V600E mutation, in formulations specifically designed for them,” said Reshema Kemps-Polanco, MBA, executive vice president of US Oncology at Novartis, in the press release. “We are thankful for the families, including children and adolescents, that participated in the clinical trial that led to this approval and whose bravery has led to a new hope for children living with this serious brain cancer.”

This FDA approval marks the sixth approval for dabrafenib and trametinib, which is indicated across multiple BRAF V600 solid tumors, including melanoma, thyroid cancer, and lung cancer. LGG is the most common pediatric brain cancer, with BRAF V600 mutations present in 15% to 20% of pediatric LGG cases. These mutations are associated with poor survival outcomes and less favorable response to chemotherapy.


Novartis Tafinlar + Mekinist approved by the FDA for pediatric patients with BRAF V600E low-grade glioma, the most common pediatric brain cancer. News release. Novartis. March 17, 2023. Accessed March 17, 2023. https://www.novartis.com/news/media-releases/novartis-tafinlar-mekinist-approved-fda-pediatric-patients-braf-v600e-low-grade-glioma-most-common-pediatric-brain-cancer

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