New treatment for brain tumour approved after over 20 years of research

The first-ever targeted treatment for brain tumours in children has been approved for NHS patients, following decades of research by a Great Ormond Street Hospital consultant.

Professor Darren Hargrave led a study, involving researchers from around the world, which found that a combination of drugs can be effective in treating children with rare cancerous brain tumours, called BRAF mutated gliomas.

Today, the the drugs Dabrafenib and Trametinib, which are already used to treat some adult cancers, have been approved the National Institute for Health and Care Excellence. This means they will be available as part of a standard care for NHS patients, rather than just those on a clinical trial.

For low-grade tumours, the new treatment could be offered as an alternative to chemotherapy. For high-grade, more aggressive tumours, it means there is another treatment option if a patient relapses.

The BRAF mutation is present in around 15-20% of paediatric low-grade tumours and around 5-10% of high-grade tumours in children.

For children with paediatric low-grade tumours, the normal course of treatment is a full surgical removal. However, for children where this is not possible additional treatments like chemotherapy are required. The low-grade trial showed the Dabrafenib and Trametinib treatment was four times more effective that chemotherapy and had fewer side effects.

For high-grade tumours, the treatment is usually surgery and then chemotherapy and radiotherapy, - but unfortunately the overall response rates to this treatment is less than 20%. When the children were treated with Dabrafenib and Trametinib in  the trial, the response rate increase to 56%.

Aaliyah

Aaliyah joined the trial after being referred for an MRI scan following a routine eye appointment. The MRI scan showed a tumour and Aaliyah was referred to Addenbrooke’s Hospital and then to GOSH.
Operating wasn’t possible and so after a year of ‘watch and wait’, the family were offered to join the TADPOLE0G trial at GOSH.
Mum Amie spent a lot of time researching the options, including speaking to other families. In 2020 they decided to join the randomized trial and Aaliyah was given Dabafenib and Trametinib, instead of chemotherapy.
She said: “We got a letter about a six-month eye check-up. We didn’t think we needed it as Aaliyah didn’t need glasses, but I thought I should ring just in case. She didn’t have any other symptoms at all, so we were so shocked – how could there by a tumour without causing any problems.
“Three months after we started the trial, we had an MRI. That was the first time I felt able to look at the scans. When I saw the before and after, that was probably the day 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.”

Aaliyah, 12, spoke about the difference the trial has made to her everyday life. She said: “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. I’ve been able to start secondary school with my friends and go to pretty much all my lessons. I’ve also been able to be at home, rather than staying in hospital for treatment, and carry on my hobbies such as majorette.
“I do feel proud in a way that I’ve been part of a trial that has helped other people and I am thankful to the team who have supported me.
“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.”

Professor Darren Hargrave has described how proud he is to see this treatment become available to NHS patients, and has looked back on all the work that has made this treatment a reality:

• Early 1980s – the BRAF gene was discovered
• 2002 - a study published in Nature identified BRAF mutations in human cancer, Professor Darren Hargrave was a research student at the Sanger Institute working on this project
• 2008-10 – multiple studies showed how the same mutations could occur in childhood cancer
• 2011 – Professor Darren Hargrave begins working with pharmaceutical companies to design a clinical trial to target these mutations with Dabrafenib and Trametinib
• 2013 – the first phase of trials for Dabrafenib and Trametinib for relapsed childhood tumours begin, with Professor Darren Hargrave leading the trials at GOSH
• 2018 – the international study, TADPOLE-G, opens. Professor Darren Hargrave was the chair of the trial steering committee
• 2019 – Results from the first phases of trials in low-grade gliomas are published, with Professor Darren Hargrave as lead author
• 2023 – Professor Hargrave publishes a paper showing Dabrafenib and Trametinib are four times more effective than chemotherapy is published following the TADPOLE-G trial
• 2024 – the treatment is approved for use in the NHS

Professor Darren Hargrave, clinical professor in paediatric neuro-oncology at GOSH, said:

“As I was involved in the original study that identified the role of BRAF in cancer and the clinical trials that led to the NICE approval of targeted therapies for childhood brain tumours with BRAF gene mutations, it is exciting to see these treatments becoming available to patients in England and Wales.

“The new combination therapy is an important advancement in the field of paediatric neuro-oncology that offers an alternative to chemotherapy for low-grade gliomas and provides an additional treatment option for relapsed high-grade gliomas, where overall response rates to the current therapy options have been as low as 20% or less.”

Professor Darren Hargrave

Replacing outdated buildings on Great Ormond Street, our new Children’s Cancer Centre will mean that children with rare and complex cancers will receive care in the best possible environment, making it easier for them to be able to play, continue with school and participate in normal activities. The CCC will also enhance our ability to research and innovate to develop new and kinder treatments for cancer.

With significant outside space, a new hospital school, child centre inpatient wards and day care spaces, imaging, theatres and critical care services linked to the existing hospital, children and young people coming to GOSH will have access to the very latest technologies and receive care and treatment in environments that reflect their needs.

For more information visit Children’s Cancer Centre.

GOSH Charity is fundraising for the Children’s Cancer Centre, find out more about how you can be part of Build it Beat it.