World-first study into precision medicine for high-risk childhood cancer yields extraordinary results

WORLD-FIRST STUDY INTO PRECISION MEDICINE FOR HIGH-RISK CHILDHOOD CANCER YIELDS EXTRAORDINARY RESULTS

VIDEO – https://www.youtube.com/watch?v=bwyugwVwNzc

In a world-first, 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.

In a study published this week 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.

A staggering 55% of children who received their personalised treatment achieved complete or partial remission, or had their disease stabilised for at least 6 months. Given that that these children had highly aggressive cancers which, in many cases, had already failed to respond to standard therapy, these are remarkable results.

These children had been observed for an average of 3 years after receiving their personalised treatment. Treatment recommendations were given to their oncologists after detailed genetic analysis of the driver genes in the tumour. This strategy matched the drug better to each child’s cancer driver genes, often suggesting drugs that are not normally used to treat that cancer type. The results show, for the first time, that this had led to an improvement in progression-free survival.

“These are very exciting results which we believe have important implications for the treatment of children with cancer,” said Professor David Ziegler, Chair of Clinical Trials for the Zero Childhood Cancer Program and senior author on the paper. “We’ve already shown that precision medicine can help identify new treatment options for many high-risk patients. Now we’ve shown that it not only can shrink their tumours, but also lead to a significant improvement in long term survival for those patients.”

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) enrolled on the Zero Childhood Cancer Program (ZERO), Australia’s national precision medicine program for children with cancer. ZERO is jointly led by Children’s Cancer Institute and Kids Cancer Centre at Sydney Children’s Hospital, Randwick and involves 9 child cancer treatment centres in the country. This study involved more than 100 scientists and clinicians working together across all these 9 child cancer centres.

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.

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.”

Prof Ziegler, who is both a paediatric oncologist at the Kids Cancer Centre and a research leader at Children’s Cancer Institute, said, “We’ve shown that matching a therapy to a patient through molecular analysis of their cancer, and implementing that targeted therapy early on, are key to achieving the best possible results.” 

Supported by the Australian Government and Minderoo Foundation and sponsored by the Australian and New Zealand Children’s Haematology and Oncology Group (ANZCHOG), ZERO’s first national precision medicine trial began in 2017, focusing on identifying new treatment options for children with high-risk cancers.

The success of this clinical trial led to joint funding of $67 million from the Australian Government ($55.8 million through the Department of Health’s Medical Research Future Fund) and Minderoo Foundation ($12.2 million) being awarded in 2020 to expand the program to be available to all 1200 Australians aged 0-18 years who are diagnosed with cancer—which was achieved in 2023. It is the first time that precision medicine has been made available to every child diagnosed with cancer, not just in Australia, but in any country in the world.

(Quote attributable to Federal Minister for Health Mark Butler)

Find out more about ZERO at https://www.zerochildhoodcancer.org.au

About ZERO Childhood Cancer

The Zero Childhood Cancer Program (ZERO) is a world-leading and Australian-first precision medicine program for children and young people with cancer. Led by Children’s Cancer Institute and the Kids Cancer Centre at Sydney Children’s Hospital, Randwick, it is a true multidisciplinary team effort of researchers and clinicians, and includes all nine of Australia’s children’s hospitals together with 22 national and international research partners.

Conducting in-depth genomic analysis for each child enrolled, ZERO aims to improve survival, reduce side effects, and advance science’s understanding of childhood cancer for the benefit of all. These advances are not only benefiting some children with cancer today, but are leading to a whole new understanding of childhood cancer that stands to revolutionise the model of care for all children with cancer in the future.

About Children’s Cancer Institute

Originally founded by two fathers of children with cancer in 1976, Children’s Cancer Institute is the only independent medical research institute in Australia wholly dedicated to research into the causes, prevention and cure of childhood cancer. More than 40 years on, our vision remains to save the lives of all children with cancer and improve their long-term health, through research. The Institute has grown to now employ over 350 researchers, operational staff and students, and has established a national and international reputation for scientific excellence. Our focus is on translational research, and we have an integrated team of laboratory researchers and clinician scientists who work together in partnership to discover new treatments which can be progressed from the lab bench to the beds of children on wards in hospitals as quickly as possible. By developing safer and more effective drugs and drug combinations, we aim to minimise side effects, giving children with cancer the best chance of cure with the highest possible quality of life. More at ccia.org.au

About Kids Cancer Centre

The Kids Cancer Centre (KCC) at Sydney Children’s Hospital, Randwick is part of Sydney Children’s Hospitals Network and has been treating children with cancer and blood diseases in NSW, Australia and the Asia-Pacific region for nearly 50 years. Almost two thirds of children treated for cancer or leukaemia at the Centre are enrolled on clinical trials, in a unique model where research and clinical care are one, ensuring the best possible care for children and their families. During that time the survival rates for children with cancer have gone from 10 per cent to nearly 80 per cent. Clinical and research staff from the Centre have made major international and national contributions to the expansion of knowledge in the area: from important discoveries around bone marrow transplantation, chemotherapy for relapsed solid tumours and leukaemia, to the invention of novel anti-cancer drug combinations and minimal residual disease testing in acute lymphoblastic leukaemia. Centre staff have been leaders in devising new methods of outreach and home nursing, and in developing modern approaches to the bereaved family. These achievements have been founded on academic excellence and clinical expertise. In the past five years alone, the Centre’s staff have published over 200 papers in peer reviewed medical and scientific journals and been awarded more than $60 million in competitive grant funding. The past 20 years has also seen a total of eight clinical staff receive the Order of Australia honours for their work. More at schn.health.nsw.gov.au

About Minderoo Foundation

Established by Andrew and Nicola Forrest in 2001, Minderoo Foundation is a modern philanthropic organisation seeking to break down barriers, innovate and drive positive, lasting change. Having invested more than $2.1 billion in the past two decades, Minderoo Foundation is proudly Australian, with key initiatives spanning from collaborating against cancer to ending plastic waste and modern slavery. More at minderoo.org. 

About Medical Research Future Fund

The Medical Research Future Fund (MRFF) is an ongoing research fund set up by the Australian Government in 2015. It provides an ongoing funding stream for important health and medical research projects.

About ANZCHOG

ANZCHOG is a non-profit organisation committed to ensuring Australian and New Zealand children receive world-class cancer care. We are the peak professional body for paediatric oncologists and health professionals who care for children with cancer, spearheading national initiatives to enhance clinical care through communication, research, networking and education. We are also the national cooperative clinical trials group for childhood cancer, actively working with trial consortia around the globe to ensure Australian and New Zealand children have the opportunity to access the latest promising cancer treatments.