DYNAMIC Trial: ctDNA-Guided Therapy Halves Chemotherapy Use in Stage II Colon Cancer Without Compromising Outcomes
This landmark RCT demonstrated that using postoperative ctDNA status to guide adjuvant chemotherapy decisions in stage II colon cancer reduced chemotherapy use from 28% to 15% while maintaining equivalent recurrence-free survival (93.5% vs 92.4% at two years). The DYNAMIC trial provided the first randomised evidence that ctDNA-based molecular residual disease testing can safely de-escalate treatment in colorectal cancer.
The original study
Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer.
- Authors
- Tie J, Cohen JD, Lahouel K, Lo SN, Wang Y, Kosmider S, et al.
- Journal
- The New England journal of medicine
- Type
- Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural
- PMID
- 35657320
Original abstract
BACKGROUND: The role of adjuvant chemotherapy in stage II colon cancer continues to be debated. The presence of circulating tumor DNA (ctDNA) after surgery predicts very poor recurrence-free survival, whereas its absence predicts a low risk of recurrence. The benefit of adjuvant chemotherapy for ctDNA-positive patients is not well understood. METHODS: We conducted a trial to assess whether a ctDNA-guided approach could reduce the use of adjuvant chemotherapy without compromising recurrence risk. Patients with stage II colon cancer were randomly assigned in a 2:1 ratio to have treatment decisions guided by either ctDNA results or standard clinicopathological features. For ctDNA-guided management, a ctDNA-positive result at 4 or 7 weeks after surgery prompted oxaliplatin-based or fluoropyrimidine chemotherapy. Patients who were ctDNA-negative were not treated. The primary efficacy end point was recurrence-free survival at 2 years. A key secondary end point was adjuvant chemotherapy use. RESULTS: Of the 455 patients who underwent randomization, 302 were assigned to ctDNA-guided management and 153 to standard management. The median follow-up was 37 months. A lower percentage of patients in the ctDNA-guided group than in the standard-management group received adjuvant chemotherapy (15% vs. 28%; relative risk, 1.82; 95% confidence interval [CI], 1.25 to 2.65). In the evaluation of 2-year recurrence-free survival, ctDNA-guided management was noninferior to standard management (93.5% and 92.4%, respectively; absolute difference, 1.1 percentage points; 95% CI, -4.1 to 6.2 [noninferiority margin, -8.5 percentage points]). Three-year recurrence-free survival was 86.4% among ctDNA-positive patients who received adjuvant chemotherapy and 92.5% among ctDNA-negative patients who did not. CONCLUSIONS: A ctDNA-guided approach to the treatment of stage II colon cancer reduced adjuvant chemotherapy use without compromising recurrence-free survival. (Supported by the Australian National Health and Medical Research Council and others; DYNAMIC Australian New Zealand Clinical Trials Registry number, ACTRN12615000381583.).