Children with rare cancer have better outcomes with added antibody treatment

Adding an antibody treatment could help children with a rare form of cancer, according to new results from a clinical trial.

Neuroblastoma is a rare type of cancer that forms in certain types of nerve tissue. In some children, their cancer does not respond to initial treatment or comes back afterwards.

New results from the BEACON trial show children who experience this could benefit from an extra antibody treatment. This would be given on top of their usual chemotherapy.

The international trial was led by Professor Juliet Gray from the University of Southampton and Southampton Children's Hospital.

Children under five most affected

Neuroblastoma primarily affects children under the age of five years.

Around 100 children between the ages of 0 and 14 years are diagnosed with neuroblastoma each year in the UK.

The cancer begins in immature nerve cells, usually in the abdomen of young children. It develops into small tumours that can be experienced as a lump in a child’s abdomen.

Neuroblastoma spreads to other parts of the body, including the bones, skin and liver, in around half of children who have it.

Shrinking tumours

The researchers trialled adding a monoclonal antibody treatment called dinutuximab beta (dB).

They recruited 65 patients, with an average age of four years. Of these, 28 patients had neuroblastoma that did not respond to treatment and 37 patients had cancer that had returned.

Adding the antibody treatment to usual chemotherapy led overall to patients' tumours shrinking after six cycles of treatment.

Children who received it had a significantly improved best objective response rate. This is a measure that represents the percentage of patients who experience a complete disappearance or partial reduction in cancer cells.

With usual treatment, the cancer reduced or disappeared in around 18 percent of patients. Adding dB improved the rate to just over 30 percent.

Better survival

Children who were given the extra treatment had an average of 11 months without the cancer progressing. This is compared to around four months for children who had usual treatment.

They also survived for longer. Children who had the added treatment had an overall survival time of almost 26 months, compared to 17 months for those who had usual care.

The results have now been published in the Journal of Clinical Oncology. Professor Gray is corresponding author of the study. She is a Professor of Paediatric Oncology and Paediatric Consultant in Southampton.

Professor Gray said: “These are really encouraging results, which will contribute towards developing better treatments for children with neuroblastoma.

“We are continuing to investigate combining dinutuximab beta with chemotherapy, called chemo-immunotherapy, in the BEACON-2 trial. This trial is now open in many UK centres, and aims to improve the chemo-immunotherapy, so that more children can benefit.”

The research was co-funded by Cancer Research UK, Imagine for Margo, Solving Kids Cancer UK and Zoe4life.

The phase 2 trial was coordinated by the University of Birmingham’s Cancer Research UK Clinical Trials Unit. Professor Amos Burke is Director of the Unit.

He said: “Neuroblastoma that comes back, or doesn’t respond to first line treatment, comes with poor outcomes currently for the children who sadly have this disease.

“These results are very important, and could improve the odds and lived experience for these children. Here at the University of Birmingham we remain focused on trialling tomorrow’s treatments for children who need them most.”

Finding the best treatment

In this trial, the researchers also measured the neurotoxicity of the treatments given. This can occur when cancer drugs cause damage or dysfunction to the brain and nervous system. It can cause symptoms like weakness, memory loss, confusion or seizures.

For patients in the dB group, around a third experienced lower grade symptoms such as drowsiness from the treatment. This was compared to 9 percent in the usual treatment group.

There were low levels of more severe grade 3 symptoms in the dB group (2.3 percent). This was comparable to the group who had usual treatment (4.5 percent).

Previously reported results from the global BEACON consortium found that adding an anti-tumour drug bevacizumab with chemotherapy drugs led to patient’s tumours shrinking. The findings led to changes in how UK paediatric oncologists treat neuroblastoma.

The further trial BEACON-2 is now investigating the difference between a combination of drugs, including bevacizumab and dB chemo-immunotherapy.