Assessing Dabrafenib and Trametinib Combination Therapy for Pediatric Glioma with BRAF V600E Mutation
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Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on October 16th, 2023
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Glioma is the most common central nervous system tumor in pediatric patients. While resection and chemotherapy have improved the 5-year survival rate to 95%, relapses still occur, necessitating the development of new therapies. About 20% of pediatric low-grade gliomas feature the BRAF V600E mutation. Consequently, a study was conducted to explore whether Dabrafenib, a selective BRAF V600E inhibitor, and Trametinib could offer similar benefits to pediatric patients as they have for adults.
The phase 2 clinical trial enrolled 110 patients between the age of 1 to 17 years old who were diagnosed with glioma according to the 2016 World Health Organization criteria. They were randomly assigned to receive either standard chemotherapy or a combination of Dabrafenib and Trametinib. Dabrafenib was administered orally twice daily, with a dose of 5.25 mg per kilogram of body weight per day for those under 12 years and 4.5 mg per kilogram per day for older participants. Trametinib was given at 0.032 mg per kilogram for patients under 6 years old and reduced to 0.025 mg per kilogram for older participants. After a median follow-up of 18.9 months, tumor shrinkage was observed in 47% of those treated with the Dabrafenib-Trametinib combination, significantly higher than the 11% response rate in the control group. In addition to tumor reduction, the combination therapy delayed tumor progression by 20.1 months, whereas tumors in the standard chemotherapy group progressed within 7.4 months. Beyond its superior effectiveness, the Dabrafenib-Trametinib combination was also better tolerated, with only half of the participants reporting serious adverse effects compared to nearly all individuals in the chemotherapy group.
The phase 2 clinical trial enrolled 110 patients between the age of 1 to 17 years old who were diagnosed with glioma according to the 2016 World Health Organization criteria. They were randomly assigned to receive either standard chemotherapy or a combination of Dabrafenib and Trametinib. Dabrafenib was administered orally twice daily, with a dose of 5.25 mg per kilogram of body weight per day for those under 12 years and 4.5 mg per kilogram per day for older participants. Trametinib was given at 0.032 mg per kilogram for patients under 6 years old and reduced to 0.025 mg per kilogram for older participants. After a median follow-up of 18.9 months, tumor shrinkage was observed in 47% of those treated with the Dabrafenib-Trametinib combination, significantly higher than the 11% response rate in the control group. In addition to tumor reduction, the combination therapy delayed tumor progression by 20.1 months, whereas tumors in the standard chemotherapy group progressed within 7.4 months. Beyond its superior effectiveness, the Dabrafenib-Trametinib combination was also better tolerated, with only half of the participants reporting serious adverse effects compared to nearly all individuals in the chemotherapy group.