• Center on Health Equity and Access
  • Clinical
  • Health Care Cost
  • Health Care Delivery
  • Insurance
  • Policy
  • Technology
  • Value-Based Care

Tumor Genome Sequencing Enables Children With Cancer to Receive Targeted Therapies


Genome sequencing of tumors from children and adolescents with recurrent or refractory cancer led to over 100 patients receiving targeted therapies.

Genomic sequencing of tumors in pediatric patients with relapsing cancer allowed for significantly more patients to receive an appropriately matched therapy, regardless of whether the therapy is standard of care, according to data from a recent study.

The study, which was published in Cancer Discovery, is the first published literature that explores the role of liquid biopsy for circulating free DNA (cfDNA) analysis among pediatric and young adult patients with recurrent or refractory malignancies.

“We wish to stress the importance of detailed comprehensive tumor board discussions for pondering the subjectivity of the treatment suggestions. Such discussions between physician-scientists, experts in new drug development and tumor diseases, as well as the treating physicians must consider potential relevance of the selected targets based on current knowledge on tumor biology and outcome in clinical trials, the expertise on novel anticancer strategies, availability of the drug, availability of an open clinical trial, as well as other treatment options that may be relevant for the patient,” the investigators wrote.

Comprehensive genomic profiling, along with improved understanding of tumor biologics and development of targeted anticancer agents, have facilitated therapeutic approaches adapted to individual cancer cases. The investigators of the Molecular Profiling for Pediatric and Young Adult Cancer Treatment Stratification (MAPPYACTS) trial, a European international prospective precision medicine trial, aimed to define the molecular profile of young patients with recurrent or refractory tumors in order to identify targeted treatments.

From January 2016 to July 2020, 774 patients with a median age of 11.6 years and who had received a liquid biopsy, were enrolled from 18 centers. Molecular profiling was done on 84% of samples from 679 patients. Among the 695 samples, 632 of them were sucessfully sequenced.

Gene alterations were considered “ready for routine use” if there was significant evidence that a drug could effectively treat tumors with the mutation. They were also deemed “potentially actionable” if evidence that an approved or investigational drug could target the mutated protein or another member of the affected signaling pathway was found.

Among the patients, 432 had potentially actionable alterations, 107 of whom were given a matched targeted therapy, either alone or in combination with chemotherapy or another targeted therapy.

Additionally, 42% of the alterations deemed “ready for routine use” were previously unknown or had not been identified by previous diagnostics. The investigators suggested the lack of detection may have been because genomic profiling tools are not used often enough to detect the alterations.

The objective response rate (ORR) was 17% for patients given a new therapy, and the disease control rate was 41%. The ORR for patients who had potentially actionable mutations that were not ready for routine use was 14%.

The study had some limitations, including that changes in treatment recommendations have changed since 2016 and many of the recommended regimens have not been extensively tested in children, raising concerns about treatment decisions, dosing, and duration.

“While selected high evidence level alterations should be part of the initial diagnostic workup, cancer complexity justifies the continuous efforts and introduction of high-throughput sequencing and treatment recommendations as a standard of care for high risk cancers," authors concluded.

"MAPPYACTS has identified future innovative diagnostic and treatment strategies, including the encouraging results of cfDNA analysis in solid extra-cerebral tumors, which are deserving of validation in further prospective studies,” the investigators said.


Berlanga P, Pierron G, Lacroix L, et al. The European MAPPYACTS trial: precision medicine program in pediatric and adolescent patients with recurrent malignancies. Cancer Discov. doi:10.1158/2159-8290.CD-21-1136

Related Videos
Joseph Alvarnas, MD.
Elli Papaemmanuil, PhD.
Hatem Soliman, MD
Patricia Deverka, MD, MS
Patricia Deverka, MD, MS
Michael Ciarametaro, MBA
Patricia Deverka, MD, MS
Patricia Deverka, MD, MS
Sneha Sharma, PharmD
Patricia Deverka
Related Content
© 2023 MJH Life Sciences
All rights reserved.