Precision-guided treatment in high-risk pediatric cancers

Recent research showed that precision medicine can identify new treatment strategies for patients with childhood cancers. However, it is unclear which patients will benefit most from precision-guided treatment (PGT). Here we report consecutive data from 384 patients with high-risk pediatric cancer (with an expected cure rate of less than 30%) who had at least 18 months of follow-up on the ZERO Childhood Cancer Precision Medicine Program PRecISion Medicine for Children with Cancer (PRISM) trial. A total of 256 (67%) patients received PGT recommendations and 110 (29%) received a recommended treatment. PGT resulted in a 36% objective response rate and improved 2-year progression-free survival compared with standard of care (26% versus 12%; P = 0.049) or targeted agents not guided by molecular findings (26% versus 5.2%; P = 0.003). PGT based on tier 1 evidence, PGT targeting fusions or commenced before disease progression had the greatest clinical benefit. Our data show that PGT informed by comprehensive molecular profiling significantly improves outcomes for children with high-risk cancers. ClinicalTrials.gov registration: NCT03336931

The development of next-generation sequencing (NGS) in conjunction with targeted anticancer therapies has allowed the delivery of precision medicine, selecting for the molecular drivers of a patient’s cancer. Pediatric precision oncology studies have identified potentially targetable molecular findings in over 65% of children with high-risk cancers1,2,3,4,5. However, clinical uptake of matched targeted therapies in these studies was generally low, ranging from 10% to 33%. One reason for low clinical uptake is physician uncertainty regarding the efficacy and benefit–risk balance of precision-guided treatment (PGT).

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