Genetic Sequencing Can Help Guide Treatment in Children with Solid Tumors
January 28, 2016
Medscape, Genome Web and HemOnc Today are among the outlets that covered this study.
Findings among the
first supporting expanding precision medicine approach in childhood cancers
genomic sequencing is feasible in pediatric oncology and can be used to
recommend therapy or pinpoint diagnosis in children with solid tumors,
according to the multicenter Individualized CAncer Therapy (iCat) study led by
investigators from Dana-Farber/Boston Children's Cancer and Blood Disorders
Center. The study, published today in JAMA Oncology, is one of the first
of its kind to be conducted in pediatric oncology. Its findings bolster the
case for matching children to treatment based on a tumor's genetic
characteristics and represent a significant step in making molecularly
targeted, personalized therapy available to children with cancer.
patients with adult cancers have benefitted greatly from a precision medicine
approach founded in clinical genomic sequencing and targeted therapies, these
gains are only beginning to reach pediatric patients. Because all
childhood cancers are rare, there are relatively little data available on the
mutations that drive pediatric tumors. Those tumors that have been sequenced
tend to harbor few genetic mutations compared to adult cancers. In addition,
because drug development efforts prioritize the needs of adult patients, relatively
few targeted drugs are currently available for children. Even when a
potentially useful targeted drug may already exist, it may lack dosing
guidelines for children or may not be formulated in ways appropriate for young
children, for instance, pill versus liquid form.
trial asked whether, given current genomic technologies and genetic knowledge,
it is even feasible to sequence pediatric tumors in a clinical context and
return recommendations based on those results. The answer, researchers concluded,
story of precision
medicine in pediatric cancer is just starting," said Katherine Janeway, MD, lead iCat investigator and clinical
director of the Solid Tumor Center at Dana-Farber/Boston Children's.
"Ours and other studies show that if we do this kind of sequencing we
might find treatment opportunities for children. And they provide openings for
expanding our knowledge of the childhood cancer genome and helping both
clinicians and basic scientists understand which treatments work for a given
tumor, which don't and why, all of which could fuel additional drug development
for both pediatric and rare adult tumors."
and her colleagues report, the iCat study collected tumor samples from 100
cancer patients seen at four centers across the United States between August
2012 and November 2013 for a variety of relapsed pediatric solid tumors. The
investigators analyzed the samples using sequencing methods that would reveal
the presence of known cancer-related alterations in 305 genes.
analysis revealed a clinically actionable genetic alteration — defined as an
alteration for which a targeted therapy was available through a clinical trial
or as an FDA-approved drug in an age-appropriate dose and formulation in the
context of a clinical trial — the team made a treatment (or iCat)
recommendation to the patient's oncologist. The team also forwarded any results
supporting a change in diagnosis or suggesting that the patient may have a cancer
predisposition syndrome. Enrolled patients were followed for a median of 6.8
study's end, the team was able to make iCat recommendations for 31 out of the
100 enrolled patients. Three of those 31 patients underwent treatment based on
the recommendation, though none responded. Among the 28 patients who did not
receive their iCat-recommended treatment, reasons included a) the patient was
ineligible for or could not otherwise access a relevant clinical trial, b) the
patient was responding well to current therapy, or c) the patient had died.
designed the study such that if we could make an iCat recommendation for 14
percent of participants, we could say that clinical sequencing was feasible,”
Janeway said. “We exceeded this benchmark."
additional 12 patients, the team identified genetic alterations suggesting a
change in diagnosis and/or revealing that the patient may have a cancer
study joins a recent and growing body of evidence supporting the feasibility
and potential benefits of incorporating clinical genomics into pediatric cancer
care. In the same issue of JAMA Oncology, a team led by investigators
from Baylor College of Medicine report similarly successful efforts to generate
genomic-based treatment recommendations for patients with pediatric solid or
brain tumors. Researchers from the University of Michigan reported similar
findings in JAMA in September 2015.
other studies are providing momentum for expanded efforts aimed at embedding
clinical sequencing more deeply into pediatric oncology practice. Janeway and
her colleagues have already launched a 12-center iCat follow-up study, the Genomic Assessment Informs Novel
therapy (GAIN) consortium study.
And in 2016, the National Cancer Institute plans to open a pediatric arm of its
Molecular Analysis for Therapy Choice
(MATCH) trial, which,
according to the NCI website, "seeks to determine whether treating cancers
according to their molecular abnormalities will show evidence of
oncology has lagged behind adult oncology when it comes to incorporating
targeted drugs and genomic testing or tumor profiling into treatment,"
Janeway said. "Together these studies indicate that we're starting to
understand how to carry out clinical sequencing in pediatric oncology and which
patients might benefit from it.”
study was supported by Hyundai Hope on Wheels, the Friends for Life Foundation
and the Gilmore Family Fund for Pediatric Oncology Research.