DYNAMIC-III
Circulating tumor DNA-guided adjuvant therapy in locally advanced colon cancer: the randomized phase 2/3 DYNAMIC-III trial
Phase 2/3N = 968
- Population
- 968 evaluable patients with stage III colon cancer, of whom 702 (72.5 percent) were ctDNA-negative.
- Design
- Multicentre randomised phase 2/3 trial in stage III colon cancer. ctDNA was tested 5 to 6 weeks after surgery and patients were assigned 1:1 to ctDNA-guided or standard management. In the ctDNA-guided arm, ctDNA-negative patients received de-escalated therapy and ctDNA-positive patients escalated therapy; clinicians prespecified the standard regimen. Primary endpoints: 3-year RFS for ctDNA-negative patients and 2-year RFS for ctDNA-positive patients. Registered as ACTRN12617001566325 (Australian New Zealand Clinical Trials Registry).
- Primary endpoint
- RFS
- Arms
- ctDNA-negative, de-escalated therapy (experimental): ctDNA-negative patients in the ctDNA-guided arm received de-escalated therapy (exact regimens not read)
- ctDNA-negative, standard management (control): ctDNA-negative patients in the standard arm received the clinician-prespecified standard regimen
- ctDNA-positive, escalated therapy (experimental): ctDNA-positive patients in the ctDNA-guided arm received escalated therapy (exact regimens not read)
- ctDNA-positive, standard management (control): ctDNA-positive patients in the standard arm received the clinician-prespecified standard regimen
- People
- Tie J, AGITG DYNAMIC-III Study Group (Intergroup Study of the Australasian Gastro-Intestinal Trials Group and Canadian Cancer Trials Group)
Δ 36-month RFS−2.8 pointsΔ 24-month RFS−10 points
Show the numbers
| Endpoint | Analysis | ctDNA-negative, de-escalated therapy / ctDNA-positive, escalated therapy | ctDNA-negative, standard management / ctDNA-positive, standard management | Effect |
|---|---|---|---|---|
| RFSctDNA-negative patients (702 of 968 evaluable) | primarymedian follow-up 47 monthsTie 2025 | 85.3% at 3 y | 88.1% at 3 y | Did not meet the noninferiority margin (the margin value is not given in the abstract). Oxaliplatin use 34.8 percent versus 88.6 percent and treatment-related hospitalisation 8.5 percent versus 13.2 percent with de-escalation versus standard. Across all evaluable patients, 3-year RFS was 87 percent in ctDNA-negative and 49 percent in ctDNA-positive patients (P < 0.001). |
| RFSctDNA-positive patients (among 968 evaluable patients; the abstract does not give their number) | primarymedian follow-up 47 monthsTie 2025 | 51% at 2 y | 61% at 2 y | Escalated therapy did not improve recurrence-free survival over standard management. No unexpected toxicity was reported. |
| Endpoint | Analysis | ctDNA-negative, de-escalated therapy / ctDNA-positive, escalated therapy | ctDNA-negative, standard management / ctDNA-positive, standard management | Effect |
|---|---|---|---|---|
| RFSctDNA-negative patients (702 of 968 evaluable) | primarymedian follow-up 47 monthsTie 2025 | 85.3% at 3 y | 88.1% at 3 y | Did not meet the noninferiority margin (the margin value is not given in the abstract). Oxaliplatin use 34.8 percent versus 88.6 percent and treatment-related hospitalisation 8.5 percent versus 13.2 percent with de-escalation versus standard. Across all evaluable patients, 3-year RFS was 87 percent in ctDNA-negative and 49 percent in ctDNA-positive patients (P < 0.001). |
| RFSctDNA-positive patients (among 968 evaluable patients; the abstract does not give their number) | primarymedian follow-up 47 monthsTie 2025 | 51% at 2 y | 61% at 2 y | Escalated therapy did not improve recurrence-free survival over standard management. No unexpected toxicity was reported. |