Tumor genome sequencing allows children with cancer to receive targeted therapies

Genome sequencing of tumors from children and adolescents with recurrent or refractory cancer has enabled more than 100 patients to receive targeted therapies.

According to data from a recent study, genomic sequencing of tumors in pediatric patients with recurrent cancer has resulted in significantly more patients receiving appropriate therapy, whether or not therapy is the standard of care.

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

“We would like to stress the importance of detailed and comprehensive tumor board discussions to reflect on the subjectivity of treatment suggestions. take into account the potential relevance of the targets selected on the basis of current knowledge on tumor biology and results of clinical trials, expertise on new anticancer strategies, availability of the drug, availability of an open clinical trial, as well as other treatment options that may be relevant to the patient,” the investigators wrote.

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

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

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

Of the patients, 432 had potentially actionable alterations, 107 of whom received appropriate targeted therapy, 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 diagnoses. The researchers suggested that the lack of detection could be due to the fact that genomic profiling tools are not used often enough to detect alterations.

The objective response rate (ORR) was 17% for patients receiving a new treatment, 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 that many recommended treatment regimens have not been widely tested in children, raising concerns about treatment decisions. , dosage and duration.

“While some high-level-of-evidence changes should be part of the initial diagnostic workup, the complexity of cancer warrants continued efforts and the introduction of high-throughput sequencing and treatment recommendations as standard of care for cancer patients. high-risk cancers,” the authors concluded.

“MAPPYACTS has identified innovative future diagnostic and treatment strategies, including encouraging results from cfDNA analysis in extra-cerebral solid tumors, which deserve to be validated in further prospective studies,” said the authors. researchers.


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

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