In a world-first precision medicine study of children enrolled in Zero Childhood Cancer Program (ZERO), Australian researchers and clinicians have shown that precision medicine – where treatment is tailored to an individual child’s cancer – leads to significantly improved outcomes in children with high risk cancer.

Luminesce Alliance funded several components of the ZERO program*, which is jointly led by two of Luminesce Alliance partners: Children’s Cancer Institute and Kids Cancer Centre at Sydney Children’s Hospital, Randwick.

In the study, published 6 June 2024 in the leading international journal Nature Medicine, the researchers found that precision medicine (also called personalised medicine) was shown to be superior to standard or non-guided therapy, both in terms of clinical response and survival.

Associate Professor Loretta Lau, a paediatric molecular oncologist at Kids Cancer Centre, researcher at Children’s Cancer Institute and first author on the paper, and Professor Glenn Marshall AM, Clinical Lead of ZERO and co-senior author on the paper, said the world-first study shows that precision medicine has the potential to change the model of care for children with cancer.

“Our study provides important new evidence that response to precision-guided therapy translates into improved survival,” said A/Prof Lau and Prof Marshall.

“This work provides some hope to families where none previously existed in a new model of treatment for high-risk childhood cancer which is changing national and international clinical practice.”

The study involved more than 100 scientists and clinicians working together across 9 child cancer centres. Over a minimum follow-up period of 18 months, the study included 384 children with high-risk cancers (with a very low chance of cure).

To determine the impact on survival, the researchers measured ‘progression-free survival’, the length of time that a patient lives without their cancer getting any worse. The results showed that children who received a ZERO-recommended treatment did significantly better than those who did not. In fact, their 2-year progression-free survival was more than double that of children who received standard therapy (26% vs 12%), and five times higher than that of children who received an unguided treatment (a novel agent not chosen on the basis of molecular findings).

Importantly, the study found that children who received their recommended therapy early on in their treatment pathway did significantly better than those who received it after their disease had progressed, suggesting that the sooner a personalised treatment strategy can be implemented, the better the chance of preventing relapse and death.

*Luminesce Alliance funded the following components of the ZERO program, mentioned in the Nature Publication:

“More recently, the INFORM study showed improved survival outcomes limited to patients with high-evidence targets2.”

• INFORM2: An exploratory multinational phase I/II combination study of Nivolumab and Entinostat in children and adolescents with high risk Malignancies – Luminesce Alliance
• The INFORM2 Clinical Trial opens in Australia – Luminesce Alliance

“The ZERO Childhood Cancer Precision Medicine Program PRecISion Medicine for Children with Cancer (PRISM) trial used whole-genome sequencing (WGS) (paired tumor-germline), and transcriptomic sequencing and DNA methylation, to identify molecular targets in high-risk cancers.”

• The Luminesce Alliance Computational Biology Program developed, benchmarked, and optimised tools for genome and transcriptome analysis for more than 970 patients enrolled in the Zero Childhood Cancer Program (ZERO) PRISM trial. These tools are now being used in subsequent expansion of the ZERO Childhood Cancer Program.

For more information

• Children’s Cancer Institute Australia announcement
• The full manuscript online at https://www.nature.com/articles/s41591-024-03044-0

About Luminesce Alliance

Luminesce Alliance is a not-for-profit cooperative joint venture between the Sydney Children’s Hospitals Network, the Children’s Cancer Institute, the Children’s Medical Research Institute, the University of Sydney and UNSW Sydney. It has been established with the support of the NSW Government to coordinate and integrate paediatric research.