NHS rolling out first targeted brain tumour treatment for children and young people

NHS England is introducing the first ever targeted treatment for children and young people with brain tumours. The newly approved combination of dabrafenib and trametinib can be taken at home and has been shown to significantly slow the progression of brain tumours called gliomas, helping people live a better quality of life for longer. 

Cancer Research UK funding helped lay the groundwork for both drugs, which can be used to treat gliomas with a specific mutation to a gene called BRAF. Our researchers also played a key role in showing how well they work together.  

Gliomas and BRAF gene mutations

Gliomas (astrocytomas) are the most common type of brain cancer in children and young people. They grow from cells in the brain or spinal cord called glial cells and are split into two types:

• Low-grade gliomas grow more slowly. Around 150 children are diagnosed with them every year in the UK.
• High-grade gliomas grow more rapidly and can often be fatal. They are also rarer: each year, doctors diagnose around 30 high-grade gliomas in children across the country.

Up to one in five low-grade gliomas, and as many as one in ten high-grade gliomas, have a mutation called BRAF V600E, which helps them grow, survive and resist traditional chemotherapies.

Dabrafenib and trametinib are known as cancer growth blockers. They work by intercepting the cancer-driving proteins made by the BRAF gene after a BRAF V600E mutation.

The evidence for dabrafenib plus trametinib

The National Institute for Health and Care Excellence (NICE) recommended the NHS offer dabrafenib plus trametinib to treat glioma after evaluating at the results of the TADPOLE-G trial.  

TADPOLE-G showed that the new drug combination stops low-grade gliomas with a BRAF V600E mutation from growing or causing new problems for an average of two years – more than three times as long as current chemotherapy options. It also supports a better quality of life. 

“I’m able to just take tablets twice a day and go to the hospital every few months, rather than be in hospital to have chemotherapy,” said Aaliyah, 12, who took part in TADPOLE-G through Great Ormond Street Hospital in London. “I’ve been able to start secondary school with my friends and go to pretty much all my lessons.” 

Patient experts told the NICE evaluation committee that chemotherapy can feel very different. They stressed that its difficult and isolating side effects can have a lasting emotional impact, or even lead to people with glioma and their caregivers choosing to stop treatment. 

“I do feel proud that I’ve been part of a trial that has helped other people, and I am thankful to the team who have supported me,” Aaliyah added. “I’m really pleased that other teenagers and children will now be able to have the tablets instead of chemotherapy, without needing to be part of a trial. That’s a pretty big thing to have been part of and will make a real difference.” 

Speaking to The Brain Tumour Charity, Aaliyah’s mum Amie remembered the day, three months into the trial, of her daughter’s first MRI since starting the new treatment.  

“That was the first time I felt able to look at the scans,” she said. “When I saw the before and after […] a massive weight was lifted off my shoulders. I didn’t expect it to shrink that much. I knew we’d made the right decision.”  

Our research into BRAF mutations

Our researchers helped show how BRAF mutations can drive cancer by creating altered BRAF proteins. Thanks to that work, drugmakers were able to develop dabrafenib to block them.

We also funded research that showed how mutations to BRAF genes can lead to changes in MEK proteins, which help cancer cells grow and survive. Trametinib was developed to block these proteins.

Once both drugs were available, we helped fund clinical trials investigating whether they could be combined to improve treatment melanoma skin cancers with the same BRAF V600E mutations as some gliomas.

Those trials demonstrated that using the two drugs together makes it harder for melanomas to develop ways of resisting them. Now, TADPOLE-G has found that the same is true for gliomas in children and young people.

Who can take these drugs and how?

Dabrafenib (Finlee) is given as tablets which are taken in the morning and the evening, while trametinib (Spexotras) doses come mixed in liquid for patients to swallow once a day. Both drugs are made by the pharmaceutical company Novartis, which has agreed to provide them to the NHS at a discount. 

In England and Wales, the NHS will start offering dabrafenib plus trametinib to children and young people aged 1-17 whose gliomas have BRAF V600E mutations over the next one to two months. 

The specific NICE recommendation reflects the fact the TADPOLE-G trial only directly compared chemotherapy to dabrafenib plus trametinib for low-grade glioma. For children and young people with these low-grade tumours, the new treatment can be used in place of chemotherapy. Those with high-grade gliomas are eligible to receive it after at least one course of radiation or chemotherapy treatment. 

NICE decisions are also usually adopted in Northern Ireland, so we hope to see dabrafenib plus trametinib being made available there soon. Novartis have announced that they also are working with the Scottish Medicines Consortium to make the drug combination available to children and young people with gliomas in Scotland.