Researchers led by Ludwig Johns Hopkins’ Yuxuan Wang and Bert Vogelstein with Ludwig Institute alumni in Melbourne, Jeanne Tie and Peter Gibbs, reported in an October publication in Nature Medicine their findings from the phase II/III DYNAMIC-III trial, which were also presented at the European Society for Medical Oncology Congress 2025. The study, which compared treatment informed by circulating tumor DNA (ctDNA) analysis to current standard of care in patients with stage III colon cancer, built on a similar study for stage II colon cancer led by the same researchers. That study, reported in March, found such analysis accurately predicted the risk of recurrence and that directing chemotherapy only to ctDNA-positive patients reduced chemotherapy use overall without compromising recurrence-free survival (RFS). The current study similarly found ctDNA to be a reliable risk marker. Treatment de-escalation guided by postsurgical ctDNA analysis led to reduced exposure to chemotherapy and fewer adverse events in patients at low risk for recurrence, with RFS approaching that achieved with standard management (85% vs. 88%). Unfortunately, patients with ctDNA-positive disease did not benefit from a ctDNA-guided escalation of therapy, suggesting a need for better therapy for these high-risk patients. The trial stems from a five-year, $10 million program launched in 2015 by the Conrad N. Hilton Foundation and the Ludwig Institute for Cancer Research for the prevention and early detection of colon cancer.
Circulating tumor DNA-guided adjuvant therapy in locally advanced colon cancer: the randomized phase 2/3 DYNAMIC-III trial
Nature Medicine, 2025 October 20