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

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