Treating Pediatric Glioma With Bevacizumab and Standard Treatment

Key Points

  • Children taking bevacizumab whose tumors had mutations in the MAPK network of genes—around 10% to 15% 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 tumors.

Children with nonbrainstem high-grade glioma could benefit from potentially life-extending treatment if genetic testing was used to personalize therapy as it is in many adults, new research published by Mackay et al in Cancer Cell reported. 

Scientists analyzed 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 centers in 14 countries—found that children whose tumors had mutations in the MAPK network of genes benefited from bevacizumab (Avastin) alongside standard treatment.

In these children, bevacizumab also appeared to cause immune cells to flood in to help destroy their tumors, raising the possibility that they could be good candidates for future immunotherapy.

Genetic Testing Needed

High-grade pediatric brain tumors 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 tumors 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 analyzed genetic, molecular, and immunologic 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 bevacizumab in children with these mutations. If successful, it would open up a whole new treatment option for a disease with very few effective therapies.

More on HERBY

This trial compared bevacizumab combined with standard treatment of temozolomide (Temodar) and radiotherapy with standard treatment alone in 121 children aged 3 to 18 with high-grade brain tumors.

The trial found that, overall, children did not benefit from the addition of bevacizumab—a drug that works by blocking a tumor’s blood supply and drawing the immune system to the cancer. But looking deeper into the genetics of the tumors revealed that children taking bevacizumab whose tumors had mutations in the MAPK network of genes—around 10% to 15% 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 tumors—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 tumors could potentially be considered for future clinical trials of immunotherapies.

Children with tumors that were driven by mutations in the histone H3F3FA gene did not benefit from bevacizumab, with an average survival of only 7.9 months, and there were very few immune cells present in and around the tumor.

Researchers at the ICR believe that testing for mutations could help direct treatment so some children are picked out for bevacizumab, and others spared treatment that is very unlikely to work for them.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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