Dabrafenib và Trametinib—Liệu pháp mới sắp ra mắt? —Tổ chức từ thiện về u não

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Clinical trial results published in August and September this year show that a promising new drug combination of dabrafenib and trametinib could help children who have a tumour with a BRAF V600 mutation. In this post we will discuss: Two separate phase II clinical trials investigated whether the combination of dabrafenib and trametinib is effective at treating low-grade and high-grade gliomas in children. Paediatric low-grade gliomas 110 children between the ages of one and 17 took part in this clinical trial. Each child had been diagnosed with a paediatric low-grade glioma with a BRAF V600 mutation. 73 children received dabrafenib and trametinib. And 37 children received carboplatin and vincristine which is the current standard of care chemotherapy. Children that received chemotherapy were able to switch to dabrafenib and trametinib if their disease progressed. The trials look place in 58 centres, in 20 different countries. 47% of children who received dabrafenib and trametinib had a complete or partial response to treatment, compared to 11% of children who received chemotherapy. Children who received dabrafenib and trametinib had a median of 20.1 months without their disease progressing, compared to 7.4 months for children who received chemotherapy. Six months after treatment, 87% of children treated with dabrafenib and trametinib showed no signs of disease progression, compared to 58% of children treated with chemotherapy. 12 months after treatment, 67% of children treated with dabrafenib and trametinib showed no signs of disease progression, compared to 26% of children treated with chemotherapy. Phase II trials also consider the safety of the drugs and this trial found that treatment with dabrafenib and trametinib had fewer serious side effects reported compared to chemotherapy (47% vs 94%) and fewer incidences of discontinued treatment compared to chemotherapy (4% vs 18%). This trial suggests that dabrafenib and trametinib treatment is better than carboplatin and vincristine chemotherapy for children diagnosed with low-grade gliomas with a BRAF V600 mutation. It appears to be effective against a wide range of paediatric low-grade gliomas. Results also suggest a clear and longer-term benefit than chemotherapy. Therefore, it presents a potential new treatment option for this type of childhood brain tumour. These results also highlight the importance of using DNA testing early during diagnosis to identify the presence of a BRAF V600 mutation. Paediatric high-grade gliomas Paediatric high-grade gliomas account for approximately 10% of childhood central nervous system tumours. They are a leading cause of childhood cancer related death. For newly diagnosed children the standard of care is often surgery, radiotherapy and chemotherapy. But there is no accepted standard of care when a tumour recurs. 41 children aged between one and 18 with an identified BRAF V600 mutation took part in the trial. All children had disease recurrence, progression or lack of response to first-line therapy. Each child was treated with dabrafenib and trametinib and where necessary, results were compared with previous studies of children diagnosed with high-grade gliomas. This is because it would be unethical not to offer treatment to these children. The trial look place in 28 different centres across 13 countries. 56.1% of children who received dabrafenib and trametinib responded to the treatment. 29.3% had a complete response (disappearance of tumour(s)) and 26.8% had a partial response to treatment (at least a 50% decrease in the size of the tumour(s)). Of the children who had complete or partial responses to dabrafenib and trametinib, the median time they responded to treatment was 22.2 months. After six months of treatment, researchers estimated that 84.7% of children were still responding to the treatment. After 12 months of treatment, researchers estimated that 62.2% of children were still responding to treatment. Dabrafenib and trametinib treatment resulted in a median of 9.0 months without a child’s disease progressing, compared to 3.5 months – the median number of months reported in other paediatric high-grade glioma studies. Following recurrence, children taking dabrafenib and trametinib lived for a median of 32.8 months, compared to just 5.6 months as reported in previous studies. Researchers also estimated that, for six months, 66.8% of children showed no disease progression, and for 12 months, 44.1% had no disease progression. The safety of this drug combination was also assessed and in this trial all children experienced at least one side effect during treatment. The most common were fever, headache, dry skin and vomiting. Overall, the treatment was determined to be safe for children with the side effects manageable and tolerated. Treatment of two children in the trial was stopped due to the development of a rash during treatment. The trial suggests that the combination treatment of dabrafenib and trametinib is a promising targeted therapy option for children with recurrence of disease and could be a potential new treatment option for this type of childhood brain tumour. Given how effective this drug combination is against both low and high-grade childhood brain tumours with a BRAF V600 mutation, it has the potential to be a future treatment option. So, we have worked with NICE – a UK body that looks at the clinical and cost effectiveness of treatments – on the assessment of dabrafenib and trametinib as a new treatment for childhood gliomas. So far, we have started to collect and prepare evidence that will help NICE understand the experience of people affected by a paediatric brain tumour diagnosis, from both a patient and carer point of view. Find out more about more about what we are doing here. Why the BRAF V600 gene is a suitable target for treatment How dabrafenib and trametinib work