Saturday, June 22, 2024

Glioma Treatment: Dabrafenib and Trametinib Approved for BRAF V600E Mutation-Positive Cases in Children and Young People Aged 1 and Over

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Glioma treatment with dabrafenib combined with trametinib is recommended as an option for treating low-grade glioma (LGG) with a BRAF V600E mutation in children and young people aged 1 year and over who require systemic treatment. It is also recommended for treating high-grade glioma (HGG) with a BRAF V600E mutation in children and young people aged 1 year and over after at least one radiation or chemotherapy treatment.

These recommendations are conditional on the treatment being provided according to the company’s commercial arrangements. Glioma is a type of brain cancer classified into LGG or HGG based on growth rate. LGG typically grows slowly, whereas HGG grows rapidly and is associated with worse outcomes. Current treatments include surgery, radiotherapy, chemotherapy, and supportive care.

Clinical Trial Evidence: For LGG, a clinical trial compared dabrafenib plus trametinib with chemotherapy in patients aged 1 to 17 years. The trial demonstrated that patients receiving dabrafenib plus trametinib experienced a longer duration before disease progression compared to those on chemotherapy.

For HGG, although direct comparisons with other treatments were not conducted, indirect comparisons suggest that dabrafenib plus trametinib provides a longer duration before disease progression than chemotherapy or best supportive care.

Cost-Effectiveness: Considering the severity of glioma, its impact on quality and length of life, and the cost-effectiveness estimates, dabrafenib plus trametinib is deemed an acceptable use of NHS resources. The most likely cost-effectiveness estimates are within NICE’s acceptable range.

Marketing Authorisation: Dabrafenib (Finlee) in combination with trametinib (Spexotras) is indicated for treating pediatric patients aged 1 year and older with LGG or HGG with a BRAF V600E mutation. The treatment is to be provided to those who need systemic therapy for LGG and those who have undergone at least one prior radiation and/or chemotherapy treatment for HGG.


Glioma Clinical Evidence: TADPOLE Study Shows Dabrafenib Plus Trametinib Improves Progression-Free Survival in LGG and HGG Patients

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Clinical Evidence: The clinical evidence comes from the TADPOLE study, which included two sub-studies:

  1. LGG Cohort: A randomized controlled trial involving patients aged 1 to 17 years with BRAF V600E mutation-positive LGG. The study found that those treated with dabrafenib plus trametinib had a significantly longer progression-free survival compared to those treated with chemotherapy.
  2. HGG Cohort: A single-arm prospective cohort study involving patients aged 1 to 17 years with BRAF V600E mutation-positive HGG. The study suggested that dabrafenib plus trametinib extended progression-free survival compared to historical data of chemotherapy and best supportive care.

Comparators and Treatment Duration: For LGG, vincristine plus carboplatin was considered the most appropriate comparator, while for HGG, the comparators were temozolomide (for those not previously treated with it) and best supportive care (for those who had prior temozolomide treatment). The recommended treatment duration is until disease progression or unacceptable toxicity, without a predefined stopping rule.

Economic Modelling and Utility Values: The economic model considered various health states and extrapolated data based on clinical evidence. Utility values were sourced from adult glioma patients due to the lack of data for children and young people, although these values may underestimate the impact on younger patients and their families.

Uncaptured Benefits and Severity Considerations: The committee acknowledged the additional benefits not captured in the QALY calculations, such as better school attendance and increased social interactions due to fewer hospital visits. It also considered the severity of the condition and applied appropriate weighting to the QALYs.

The committee concluded that dabrafenib plus trametinib offers a valuable new treatment option for children and young people with BRAF V600E mutation-positive glioma. Despite some uncertainties in the clinical and economic evidence, the overall benefits, including the potential for improved quality of life and the unmet need for effective treatments, justify its recommendation as a cost-effective use of NHS resources. Thus, dabrafenib plus trametinib is recommended for treating both low-grade and high-grade glioma in the specified patient population.

Resource: National Institute for Health and Care Excellence, May 29, 2024

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