Children with incurable brain tumours could benefit from
potentially life-extending treatment if genetic testing was used
to personalise therapy as it is in many adults, major new
research reports.
Scientists analysed the DNA of children taking an adult cancer
drug on a clinical trial deemed to have ‘failed’, and found that
many with particular genetic traits had actually responded well
to treatment.
Some of these children survived more than a year longer than
others on the trial.
The international study – led by a team at The Institute of
Cancer Research, London, and involving 51 centres in 14 countries
– found that children whose tumours had mutations in the MAPK
network of genes benefited from Avastin (bevacizumab) alongside
standard treatment.
In these children, Avastin also appeared to cause immune cells to
flood in to help destroy their tumours – raising the possibility
that they could be good candidates for future immunotherapy.
Children’s aggressive, or ‘high grade’, brain tumours are
currently treated as one disease, but a recent genetic analysis
by the same team at The Institute of Cancer Research (ICR) showed
they were actually at least 10 different diseases.
The new research shows the benefits of testing children for
genetic mutations in their tumours to make sure they receive the
treatment most likely to work.
Increasingly, treatment of adult cancers is shaped by genetic
testing, but children’s cancer continues to lag behind.
The new independent academic study – published today (Monday) in
the prestigious journal Cancer Cell and funded
by Roche – analysed genetic, molecular and immunology data from
the HERBY phase II clinical trial after it had been completed.
The researchers will now look to confirm the findings in a
clinical trial set up specifically to test the effectiveness of
Avastin in children with these mutations. If successful, it would
open up a whole new treatment option for a disease with very few
effective therapies.
This trial compared Avastin combined with standard treatment of
temozolomide and radiotherapy with standard treatment alone in
121 children aged three to 18 with high-grade brain tumours.
The trial found that, overall, children did not benefit from the
addition of adult cancer drug Avastin – a drug that works
by blocking a tumour’s blood supply and drawing the immune
system to the cancer.
But looking deeper into the genetics of the tumours revealed that
children taking Avastin whose tumours had mutations in the MAPK
network of genes – around 10-15 per cent of the total – survived
up to 16 months longer than other patients.
These children also saw many more immune cells called killer T
cells flock to the site of their tumours – in some cases because
their cancers had more mutations overall and so were easier for
the immune system to pick apart from healthy cells.
Children with these tumours could potentially be considered for
future clinical trials of immunotherapies, which tend to work
best in patients whose cancers have already sparked some immune
reaction.
Children with tumours that were driven by mutations in the
histone H3F3FA gene did not benefit from Avastin, with an average
survival of only 7.9 months, and there were very few immune cells
present in and around the tumour.
Researchers at the ICR – a research institute and charity –
believe that testing for mutations could help direct treatment so
some children are picked out for Avastin, and others spared
treatment that is very unlikely to work for them.
Although rare, aggressive childhood brain tumours are the biggest
cause of cancer-related death under 19 years of age because
survival rates are so poor – children with these tumours are only
expected to live an average of nine to 15 months.
Study leader Professor , Professor of Childhood
Brain Tumour Biology at The Institute of Cancer Research, London,
said:
“We will never see progress in treatment of children’s brain
cancers while we continue to lump everyone with these cancers
together in one group. Children deserve better.
“Our research has previously shown that children’s brain cancer
is really 10 different diseases, and our new study found these
genetic differences can have a major impact on how children
respond to drugs. We are building up evidence that genetic
testing in children with cancer can have real benefits for
selecting the best treatment.
“The next step is to confirm our findings in a clinical trial
where only children with these specific mutations receive
Avastin. If that is successful, we can open up a promising new
option for paediatric brain cancer by turning an established drug
for adult cancers into a targeted treatment for children.”
Professor Paul Workman, Chief Executive of The Institute
of Cancer Research, London, said:
“We’ve seen dramatic progress in the treatment of adult cancers,
through advances such as the introduction of targeted therapies
and more recently immunotherapies. But that progress hasn’t yet
been matched in children.
“This exciting research is giving us the tools to personalise
treatment for children with brain cancer. It’s vital that we take
advantage of advances in research by improving children’s access
to genetic testing and clinical trials, so every child has the
best possible chance of receiving a drug that may work for them.”
