Monday, October 20, 2025 Berlin, 20 October 2025AGITG DYNAMIC-III clinical trial findings published in Nature Medicine and presented at the Presidential Symposium of the European Society for Medical Oncology Congress in Berlin, GermanyGlobally significant results show circulating tumour DNA (ctDNA) is feasible to guide treatment choices for stage 3 colon cancerThe randomised Phase 2/3 clinical trial randomised 1,002 patients from Australia, Aotearoa New Zealand, and Canada Key findings:ctDNA is a strong warning signal:People with no ctDNA detected had much better outcomes than those with ctDNA detected (3-year recurrence-free survival: 87% vs 49%).Among ctDNA-positive patients, a higher ctDNA level meant higher risk of the cancer coming back.Recurrence risk is lowfor ctDNA-negative patients with a 3-year recurrence-free survival of 87%.ctDNA-informed treatment de-escalation is feasible and resulted in markedly reduced oxaliplatin usage (88.6% à 34.8%) and less hospitalisations from treatment side effects.ctDNA is a powerful tool to guide and personalise treatment choices.The AGITG DYNAMIC-III colon cancer study, led by the Australasian Gastro-Intestinal Trials Group (AGITG) in collaboration with the Canadian Cancer Trials Group (CCTG), has reported results from the primary analysis of the ctDNA-negative cohort. The findings were announced by Professor Jeanne Tie, Australian Study Chair and medical oncologist at the Peter MacCallum Cancer Centre (Peter Mac), during the Presidential Symposium of the European Society for Medical Oncology Congress in Berlin, Germany.Simultaneously published in Nature Medicine, the findings provide evidence to the use of ctDNA as a powerful tool to guide treatment choices for people with stage 3 colon cancer. Almost 11,000 Australians are diagnosed each year with colon cancer, making it one of the most common cancers. Following surgery, most patients receive 3 to 6 months of oxaliplatin-based chemotherapy, but it is unclear how much each individual patient will benefit. This treatment has the potential for substantial toxicity and impact of quality of life.DYNAMIC-III explored using circulating tumour DNA (ctDNA) as a prognostic marker to inform adjuvant treatment selection. Patients were tested for ctDNA 5-6 weeks after surgery and randomised to either standard management or a ctDNA-guided approach. In the ctDNA-guided arm, patients with a negative ctDNA result could receive less intensive treatment, such as shorter chemotherapy duration, switching from a doublet to single-agent therapy, or, in some cases, observation alone.“For many patients, the prospect of chemotherapy is daunting,” says Professor Jeanne Tie. “Our study shows that if no tumour DNA is detected after surgery, patients may do just as well with less intensive chemotherapy – this means fewer side effects, less disruption to daily life, and more time living well after cancer.”The results from the ctDNA-negative group showed that de-escalating treatment resulted in markedly reduced usage of oxaliplatin chemotherapy after surgery (88.6% à 34.8%) and less hospitalisations from treatment side effects. The findings show that a ctDNA blood test after surgery can help identify patients into lower-risk and higher-risk groups for their cancer returning. For those who are lower risk, using ctDNA testing to reduce how much chemotherapy they receive can spare many people from the tough side effects with only a very small trade-off in overall survival outcomes (3-year recurrence-free survival 85.3% vs 88.1%). This trial highlights ctDNA as a powerful tool to guide treatment choices and help identify which patients might safely receive less treatment and which might need more effective options.“The AGITG DYNAMIC-III trial findings represent significant progress in understanding the role of ctDNA in informing colon cancer treatment. Using ctDNA, we can gain a more precise understanding of patients’ individual risk. More than 1,000 patients participated in this study, and we thank everyone for contributing to this crucial step forward,” says Professor Tie.Between October 2017 and April 2023, 1,002 patients were randomised in the AGITG DYNAMIC-III trial, with 66 sites open across Australia, Aotearoa New Zealand, and Canada. International collaboration was crucial to the recruitment success of this trial.“This study provides the best available prospective evidence of the prognostic value of ctDNA in selecting adjuvant chemotherapy for patients with resected stage III colon cancer. Its results are crucial as we build the evidence needed to move ctDNA into the clinic and we are thrilled to work with our Australian collaborators on this very important trial,” says Dr Jonathan Loree, DYNAMIC-III Canadian Study Chair, oncologist at BC Cancer, and CCTG Senior Investigator.The Canadian Cancer Society, the Canadian Institutes of Health Research, and the Marcus Foundation provided funding for AGITG DYNAMIC-III.Nature Medicine publication Trial details:About the trial Design: Multi-centre, randomised, phase 2/3 trial.Population: Patients with stage 3 colon cancer.Intervention: ctDNA-guided management, where ctDNA-negative patients could receive reduced adjuvant chemotherapy.Comparator: Standard management, with chemotherapy determined by clinician choiceEndpoint: Primary endpoint was 3-year recurrence-free survival (RFS).Scale: 66 sites were open across Australia, Aotearoa New Zealand, and Canada. 1,040 participants were recruited, with 1,002 randomised.ResultsOf 968 evaluable patients, 702 (72.5%) were ctDNA-negative; 353 were assigned to ctDNA-guided treatment and 349 were assigned to standard management. 319 (90.4%) patients received ctDNA-guided treatment per-protocol de-escalation. Treatment de-escalation reduced oxaliplatin-based chemotherapy use versus standard management (34.8% vs. 88.6%, P < 0.001) and lowered severe adverse events of special interest (6.2% versus 10.6%, P=0.037) and treatment-related hospitalisation (8.5% vs. 13.2%, P = 0.047). Non-inferiority of ctDNA-guided de-escalation was not confirmed though outcomes were close, with a 3-year recurrence-free survival (RFS) of 85.3% versus 88.1% (difference, -2.8%; 97.5% lower CI, -8.0%). Subgroup analysis suggested de-escalation may be non-inferior in clinical low-risk (T1-3N1) tumours (3-year RFS, 91.0% vs. 93.2%; difference, -2.2%; 97.5% lower CI, -7.2%).ConclusionThe DYNAMIC-III study concluded that stage III colon cancer patients with negative post-surgery ctDNA had low recurrence risk. ctDNA-guided de-escalation is feasible, substantially reduces oxaliplatin exposure and adverse events, with outcomes approaching standard management, especially in clinical low risk tumours.This trial’s findings encourage further research into ctDNA-informed de-escalation strategies. -----About the Australasian Gastro-Intestinal Trials GroupThe Australasian Gastro-Intestinal Trials Group (AGITG) is a multi-disciplinary collaborative group that undertakes patient-centric research to advance medical care and practice in the treatment of gastro-intestinal cancer. Since 1991, the AGITG has led 83 GI cancer research studies, enrolling 9,400 patients across 285 sites worldwide. Learn more About the Canadian Cancer Trials Group The Canadian Cancer Trials Group (CCTG) is a cancer clinical trials research cooperative that runs phase I-III trials to test anti-cancer and supportive therapies at over 85 hospitals and cancer centres across Canada. From their operations centre at Queen's University, CCTG has supported more than 600 trials enrolling 100,000 patients from 40 countries on 6 continents through a global network of 20,000 investigators and clinical trial staff. CCTG is a national program of the Canadian Cancer Society and their aim is to improve survival and quality of life for all people with cancer. For further information, please visit: www.cctg.ca About Peter MacPeter MacCallum Cancer Centre is a world leading cancer research, education and treatment centre and Australia’s only public health service dedicated to caring for people affected by cancer. Peter Mac has 4,200 employees, including more than 700 laboratory and clinical researchers, all focused on providing better treatments, better care and potential cures for cancer ContactAGITGErin Burgess, Head of Communicationserin@gicancer.org.au Canadian Cancer Trials GroupLisa Callahan, Communications Leaderlcallahan@ctg.queensu.ca Peter MacCallum Cancer CentreDavid Walsh, Director, Communicationsdavid.walsh@petermac.org -----
