Journal Article

Precision-guided treatment in high-risk pediatric cancers

Cowley, Mark J., Fleuren, Emmy D. G., Lau, Loretta M. S., Ekert, Paul G., Barahona, Paulette, Haber, Michelle, Marshall, Glenn M., Wood, Paul J., Lock, Richard B., Gifford, Andrew J., Diamond, Yonatan, Lin, Angela, Nicholls, Wayne, Yeung, Veronica, Dalla-Pozza, Luciano, Ziegler, David S., Nagabushan, Sumanth, Zhukova, Nataliya, Senapati, Akanksha, Moore, Andrew S., Ajuyah, Pamela, Sherstyuk, Alexandra, Alvaro, Frank, Mayoh, Chelsea, Kotecha, Rishi S., Tapp, Heather, Fuentes-Bolanos, Noemi A., Tyrrell, Vanessa, Hansford, Jordan R., Jessop, Sophie, Cui, Louise, Mateos, Marion K., Sullivan, Ashleigh, Battaglia, Lauren, McCowage, Geoffrey, Altekoester, Ann-Kristin, Eisenstat, David D., Trahair, Toby N., Omer, Natacha, Khaw, Seong-Lin, Khuong-Quang, Dong-Anh, Wong, Marie, Gottardo, Nicholas G., Manoharan, Neevika

2024

Overview

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 In the observational ZERO Childhood Cancer Precision Medicine Program PRecISion Medicine for Children with Cancer (PRISM) trial, children with high-risk cancer were treated with molecular tumor board-recommended therapies, resulting in overall clinical response rates that translated into survival benefit after long-term follow-up.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/67/1059/602 / 631/67/2332 / 631/67/69 / 692/308/575 / Adolescent / Biomedical and Life Sciences / Biomedicine / Cancer / Cancer Research / Child / Child, Preschool / Children / Female / Health risks / Health services / Humans / Infant / Infectious Diseases / Male / Metabolic Diseases / Molecular Medicine / Neoplasms - drug therapy / Neoplasms - genetics / Neoplasms - therapy / Neurosciences / Patients / Pediatrics / Precision medicine / Precision Medicine - methods / Progression-Free Survival / Risk / Survival / Treatment Outcome