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Combination therapy boosts progression-free survival in pediatric brain cancers


Photo credit – University College of London

CANCER DIGEST – Dec. 1, 2023 – A new combination therapy for childhood brain cancer reduced side effects from chemotherapy, increased the response rate four-fold, and increased progression-free survival almost three times, in early results of the TADPOLE G clinical trial published in the Nov. 20, 2023 Journal of Clinical Oncology.


The study led by Professor Darren Hargrave, of University College of London’s Great Ormond Street Institute of Child Health follows on to the earlier small trial testing safety and effectiveness of the drug combination.


Gliomas are cancers of the glial brain cells that support neurons. It is a common form of brain cancer that accounts for about 25 percent of cancers in children. Low grade gliomas are usually treatable with surgery, but for patients where surgery is not possible additional treatments including chemotherapy are required. These patients often experience multiple relapses, further disease progression and serious side effects.


In the clinical trial, 73 patients with low-grade gliomas with a specific mutation in a gene called BRAF were treated with standard chemotherapy and a combination of dabrafenib and trametinib that target BRAF mutated gliomas. Their outcomes were compared with 37 patients treated with the standard chemotherapy alone.


The early results showed overall response rate for the combination group was four times better than the chemo only group. In addition, progression of the cancer was halted a median of 20 months in the combination group compared to 7.4 months in the chemotherapy group.


Results in a separate trial of 41 children previously treated with chemotherapy for high-grade gliomas, achieved similar results with 56 percent responding to the treatment with a median duration of progression-free survival of 22.2 months.


Dr. Hargrave said the promising results suggest targeted therapies may offer improved outcomes for cancers with specific gene mutations.


“The results of these studies highlight how targeted drug therapies can offer patients new treatment avenues that not only improve outcomes but reduce the side effects often associated with cancer therapies,” he said in a press release.


Dabrafenib and trametinib are being used to treat melanoma and non-small cell lung cancer in patients with mutations in the BRAF gene. They were FDA approved for treatment of BRAF-positive pediatric gliomas in March 2023.


Source: University College of London press release






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