Abstract
The Institute of Cancer Research and the Royal Marsden NHS Foundation Trust have launched the United Kingdom's first pediatric genetic testing program. The groups aim to bring the same precision medicine options to children that are currently available to many adults with cancer.
The Institute of Cancer Research (ICR) and the Royal Marsden NHS Foundation Trust have launched the United Kingdom's first pediatric genomic testing program. The pilot program aims to bring targeted therapies to children with cancer based on the mutations in their tumors.
“Currently, the UK does not have a robust program for prospective genomic characterization of children with cancer,” says the study's leader, Louis Chesler, MD, PhD, a pediatric oncologist and professor of pediatric cancer biology at the ICR. “Our primary goal is to construct a genomically driven, multiarmed therapy trial in order to match patients to the best targeted drugs based on their molecular fingerprint.”
The initiative is already under way at the Royal Marsden Hospital in London and will be rolled out at 20 other hospitals across the UK over the next 2 years, explains Chesler. About 400 children ages 14 and younger with any type of solid tumor can receive the test, which sequences 81 genes commonly mutated in pediatric cancers.
Researchers will focus initially on the most common tumor types affecting the brain, nerves, and muscles, but hope to expand into all solid tumors as well as leukemia and lymphoma, he says. ICR's data will be available to researchers in the United States and Europe via an online repository.
When possible, the children will be directed to trials of targeted therapies based on the test results, something that is already happening on a small scale at the Royal Marsden, says Chesler. The goal is to make targeted drugs available to all children at diagnosis, as opposed to waiting until they relapse following standard treatment.
Significant barriers remain, however, as clinical trials generally aren't conducted as efficiently or quickly in children, partly due to the rarity of childhood tumors and the difficulty of enrolling a sufficient number of patients, he says. Routine sequencing could help change that by making it possible for researchers to design pediatric clinical trials based on a growing database of molecular tumor profiles rather than on particular tumor types, he adds.
Chesler and his colleagues aim to set up a pediatric trial similar to the NCI-MATCH trial in the United States, which runs multiple experimental arms and matches patients to therapies based on the molecular profiles of their tumors. The pediatric counterpart of MATCH is slated to open this year.
“Once you sequence thousands of patients, you can look at the significance of a genetic change in each kind of cancer and associate it with patients' clinical information,” says Chesler. “Then the sequencing information becomes much more powerful as a tool to predict outcomes and select appropriate therapies.”
Recent research suggests that genetic testing can help guide children to more effective therapies, says John Maris, MD, a professor of pediatrics at the Children's Hospital of Philadelphia and the University of Pennsylvania. For example, in a recently published study, researchers sequenced tumors from 91 children and young adults and found potentially actionable mutations in 46%, some of which triggered changes in treatment (JAMA 2015;314:913–25).
However, the study's authors highlighted significant barriers to delivering appropriate therapies, notes Maris, including a dearth of pediatric clinical trials and often nonexistent pediatric dosing information. As a result, they may be prevented from accessing potentially effective treatments even if an appropriate targeted therapy exists.
“The pediatric oncology community is facing the very urgent issues of defining proper mutation drug matches, making sure they work in the preclinical setting, and figuring out how to get them to children,” says Maris. “Routine genetic sequencing and prospective clinical trials in children are the first steps toward breaking down those barriers.” –Janet Colwell
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