Pediatric MATCH Trial Discovers More Targetable Genetic Alterations in Pediatric Cancers

An interim analysis of more than 400 patients screened via the National Cancer Institute-Children’s Oncology Group Pediatric Molecular Analysis for Therapy Choice (NCI-COG Pediatric MATCH) trial estimated that tumor sequencing in younger patients with treatment-refractory cancers had genetic alterations matching a novel targeted therapy in significantly more study participants than initially estimated. The findings were shared on a presscast held in advance of the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting.

In the presscast, study author Donald Williams Parsons, MD, PhD, associate professor of pediatrics and oncology at Baylor College of Medicine, noted that this is the first nationwide precision oncology trial for children.

Dr Parsons reported that study enrollment has met projections through nationwide COG participation. “So there’s been significant enthusiasm for such a study from both our oncologists, as well as our patients and families,” he said in the presscast. The NCI-COG Pediatric MATCH will enroll at least 1000 children with treatment-refractory cancers.

When the trial first launched in 2017, it was estimated that tumor sequencing in children, adolescents, and young adults with cancers that do not respond to treatment would identify genetic alterations that matched an investigational targeted therapy in 10% of study participants.

According to the presscast, this expectation was based on experience from pediatric disease-specific research studies, the majority of which had focused on newly diagnosed pediatric cancers instead of treatment-refractory tumors, as well as similar adult trials, such as the NCI-MATCH study. However, the number was much higher than previously expected, with 24% of participants eligible to receive treatment with at least 1 drug being treated in trial.

The targetable alterations detected in Pediatric MATCH patients involved diverse cancer genes: most commonly RAS gene mutations, BRAF mutations or fusions, SMARCB1 mutations or deletions, and NF1 mutations, according to the study.

“We’re encouraged by these early results that underscore the value of public-private collaboration in understanding and treating cancers occurring in children, adolescents, and young adults,” said NCI study chair Nita Seibel, MD, in a press release about the findings. “Pediatric MATCH depends on active partnership between NCI, COG, the US Food and Drug Administration, pharmaceutical companies, and other key pediatric cancer research stakeholders.”

To date, only a small number of targeted therapies have been approved for the treatment of pediatric cancers.

However, Dr Parsons said that NCI-COG Pediatric Match has created a nationwide framework for molecular testing of pediatric cancers.

“This study is allowing us to evaluate targeted therapies or specific types of investigational drugs in patients with many different cancer types, some common, some very rare.” he concluded. “So hopefully we can effectively study these agents and identify signals of activity where some of these drugs may work for our patients.”

References

Pediatric MATCH Trial Finds More Frequent Targetable Genetic Alterations in Pediatric Cancers Than Predicted [news release]. ASCO. https://www.asco.org/about-asco/press-center/news-releases/pediatric-match-trial-finds-more-frequent-targetable-genetic. Accessed May 15, 2019.