Written by Charlotte Harrison, Science Writer
The results from a clinical trial that sequenced DNA and RNA in tumours from paediatric and adolescent cancer patients experiencing a relapse has enabled over 100 of them to receive a targeted therapy that is not the current standard of care.
The European trial — with the acronym MAPPYACTS — ran from 2016 to 2020, and used whole exome sequencing and RNA sequencing to determine the molecular profile of 326 tumour biopsies to determine the best salvage treatment.
Targeted treatment suggestions
The researchers found that around two-thirds of the patients had at least one genetic alteration that led to a targeted treatment suggestion. The targeted treatment suggestion was classed as “ready for routine use” if there was significant clinical evidence that a drug could effectively treat tumours with a particular mutation; this criterion applied to around 10% of patients. Of the 356 patients with follow-up beyond 12 months, 107 received one or more targeted therapies that matched their mutation; over half of these therapies were in early-stage clinical trials.
Overall, patients who received a targeted treatment suggestion had a 17% objective response rate, and patients whose treatment suggestion was “ready for routine use” had a response rate of 38%. Notably, almost half of the “ready for routine use” alterations were previously unknown or had not been identified by previous diagnostics.
Circulating tumour DNA
The researchers also investigated the possibility of using small fragments of tumour-cell DNA that circulate in the blood — known as cell-free DNA (cfDNA) — to identify druggable mutations. This is one of the first studies to explore the use of liquid biopsies for analysing cfDNA in young patients.
Although the researchers did not make treatment decisions based on this part of the study, they sequenced cfDNA from 128 patients and found over 90 mutations that might be amenable to a targeted treatment suggestion. Many of these mutations were not detected by sequencing the tumour, highlighting that cfDNA analysis can pick up tumour heterogeneity that traditional biopsies may miss.
The study has several shortcomings, including the fact that treatment recommendations have evolved since the study began in 2016, and many of the treatments have not been fully researched in children, which can complicate decisions about dosing and duration. Nevertheless, the authors note that, “cancer complexity justifies the continuous efforts and introduction of high-throughput sequencing and treatment recommendations as a standard of care for high-risk cancers”.
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