Jeanne Tie, MD, Peter MacCallum Cancer Centre, Melbourne, Australia, discusses findings from the DYNAMIC-III trial, which evaluated a ctDNA-guided approach to adjuvant chemotherapy in patients with stage 3 colon cancer. 

The trial found that tailoring treatment based on post-surgery ctDNA results significantly reduced oxaliplatin use and treatment-related toxicity, with recurrence-free survival outcomes closely matching standard management, particularly in patients with low-risk disease.

These results were presented at the 2025 European Society of Medical Oncology (ESMO) Congress in Berlin, Germany.

Transcript: 

Hi, I am Jeanne Tie, I'm a medical oncologist specializing in colorectal cancer from Peter MacCallum Cancer Centre in Melbourne, Australia. At ESMO Congress 2025, I'll be presenting results on the primary analysis from the ctDNA-negative cohort of the DYNAMIC-III trial, the first randomized study in stage 3 colon cancer to test a ctDNA-guided adjuvant treatment strategy. 

The simple and important question we are asking in this study is: can we safely reduce chemotherapy in patients who do not have molecular evidence of residual disease? The background to this is that even though 3 to 6 months of oxaliplatin-based chemotherapy is standard of care for stage 3 colon cancer patients, for the majority of individual patients the absolute benefit remains uncertain, but patients do experience significant toxicity, particularly oxaliplatin-related neuropathy. Post-operative ctDNA has emerged as one of the most powerful prognostic factors and we believe that it could be used to inform a risk-adapted treatment approach. 

The study randomized just over 1000 patients across 66 institutions from Australia, New Zealand, and Canada and 73% of patients tested negative for ctDNA and were then randomized to the ctDNA-informed arm, whereby if they were negative, patients de-escalated treatment from their pre-planned chemotherapy—either omitting oxaliplatin or shortening the total duration of their chemotherapy. Patients in the standard of care arm received treatment of choice as per clinician’s discretion, blinded to the ctDNA results. The primary end point was 3-year recurrence-free survival [RFS]. 

The key finding from the study was that the de-escalation strategy had a high compliance rate—about 90%—and managed to reduce the use of oxaliplatin doublet chemotherapy from nearly 89% in standard of care down to 35% with ctDNA guidance. This de-escalation of treatment led to significantly less treatment-related hospitalization as well high-grade treatment-related adverse events of interest such as diarrhea, mucositis, and nausea. At a median follow-up of 47 months, the 3-year recurrence-free survival with ctDNA guidance was 85.3% and with standard management 88.1%, an absolute difference of 2.8%. Unfortunately, given that the lower bound of the confidence interval for this difference was –8%, which slightly missed the pre-specified non-inferiority margin of –7.5%, non-inferiority could not be formally met. Nonetheless, the difference was small. Importantly, in subgroup analyses of clinical risk—low risk versus high risk—given that this is the strongest clinical factor currently driving adjuvant chemotherapy intensity in the clinic. We found that patients with clinically low-risk, ctDNA-negative testing had very favorable outcomes with 3-year RFS exceeding 90% across both groups: 91% with ctDNA guidance and 93.2% with standard management. In contrast, outcomes were less favorable for clinically high-risk, ctDNA-negative patients, and the differences were more pronounced, with an absolute difference of about 5.8%. 

What does this mean for patients and for clinical practice? It’s very clear that patients with ctDNA-negative stage 3 colon cancer have a good prognosis and low recurrence risk, with an overall 3-year RFS of 87%. We now know that ctDNA-guided de-escalation is operationally feasible, is well adhered to, and results in less oxaliplatin use and a better toxicity profile. While we could not formally demonstrate non-inferiority compared to standard care, the difference in outcomes is small. The outcomes are similar—particularly close for clinically low-risk disease. We believe that, together, these findings will help guide individualized risk–benefit discussions with patients and lay the foundation for ongoing efforts to reduce chemotherapy use through ctDNA-guided strategies.

Source:

Tie J, Wang Y, Loree JM, et al. ctDNA-guided adjuvant chemotherapy de-escalation in stage III colon cancer: Primary analysis of the ctDNA-negative cohort from the randomized AGITG DYNAMIC-III trial (Intergroup study of AGITG and CCTG). Presented at the 2025 ESMO Congress. October 17-21, 2025; Berlin, Germany. LBA9