Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer: 5-year outcomes of the randomized DYNAMIC trial
- Study type
- Clinical trial
- Study name
- DYNAMIC
- Phase
- Phase 2
- Design
- Report of prespecified analyses (and one post hoc analysis) of the randomised DYNAMIC trial (2:1 randomisation); registration: ACTRN12615000381583
- Sample size
- 455 patients randomised in the original trial (302 ctDNA-guided, 153 standard)
- Source
- Nat Med · 2025
In plain words
This report followed the patients of the DYNAMIC study for 5 years. The result is reassuring: patients who were spared chemotherapy based on the ctDNA blood test stayed just as well and were just as likely to be alive after 5 years. Also, in ctDNA-positive patients who received chemotherapy, clearing of ctDNA from the blood at the end of treatment was a very good sign.
Key results
Treatment arms and regimens
Adjuvant chemotherapy only for patients ctDNA-positive at week 4 or 7 after surgery; ctDNA-negative patients were followed without chemotherapy. Permitted regimens in both groups: single-agent fluoropyrimidine (modified de Gramont, QUASAR, Roswell Park or capecitabine) or an oxaliplatin doublet (mFOLFOX6 or CAPOX/XELOX); a protocol amendment in February 2018 allowed 3 months of treatment, and dose modification was per centre standard. Doses per the ANZCTR registration:
- Modified de Gramont every 2 weeks: leucovorin 50 mg IV, fluorouracil 400 mg/m² IV, then 2400 mg/m² continuous IV infusion by pump over 46 hours.
- Modified QUASAR weekly: leucovorin 50 mg IV and fluorouracil 375 to 450 mg/m² IV (per centre standard).
- Modified Roswell Park weekly (6 weeks then 2 weeks' rest): leucovorin 50 mg IV and fluorouracil 500 mg/m² IV.
- Capecitabine: orally on days 1 to 14 every 21 days (dose per centre standard).
- mFOLFOX6 every 2 weeks: oxaliplatin 85 mg/m² IV, leucovorin 50 mg IV, fluorouracil 400 mg/m² IV and 2400 mg/m² continuous infusion over 46 hours.
- XELOX/CAPOX every 3 weeks: oxaliplatin 130 mg/m² and capecitabine 1000 mg/m² twice daily orally on days 1 to 14 every 21 days.
In the original trial, 62% of treated patients in this group received an oxaliplatin-based regimen and median treatment duration was 24 weeks.
Decision on adjuvant chemotherapy based on clinical and pathological criteria, with the same permitted regimens and doses; in the original trial, 90% of treated patients in this group received single-agent fluoropyrimidine (median treatment duration 24 weeks).
Source of the regimen details: Names of permitted regimens and the 3-month amendment: full text of the paper (PMC12974608, Methods section); doses: ANZCTR trial registration (ACTRN12615000381583); regimen received: full text of the original DYNAMIC trial (PMC9701133)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
The same population as the DYNAMIC trial: stage II (T3 or T4, N0, M0) colon or rectal adenocarcinoma with complete resection and negative margins; ECOG 0 to 2; suitable for oxaliplatin- or fluoropyrimidine-based adjuvant chemotherapy; no macroscopic metastases on CT of the chest, abdomen and pelvis within 8 weeks before enrolment; enrolment within 3 weeks after surgery. Rectal cancer patients who had received neoadjuvant chemoradiotherapy or were planned for postoperative chemoradiotherapy, synchronous primary colorectal cancer, and another primary cancer in the previous 3 years (except non-melanoma skin cancer and carcinoma in situ of the cervix) were excluded.
Endpoints
Prespecified analyses: 5-year recurrence-free survival (RFS), overall survival (OS), ctDNA clearance at the end of chemotherapy and the association of ctDNA level with outcome. Post hoc analysis: ctDNA clearance with a new assay covering more mutations.
Safety and side effects
No new safety data are reported; because only standard treatments were used, adverse events were not assessed in this trial.
Clinical significance and place in guidelines
These mature data showed that omitting chemotherapy in ctDNA-negative patients with stage 2 disease had no adverse effect on recurrence-free or overall survival up to 5 years later, providing important support for the ctDNA-guided approach. ctDNA testing after the end of treatment and ctDNA level were proposed as possible tools for further risk stratification, which still require prospective validation.
Limitations
Phase 2 trial with limited statistical power for overall survival; the ctDNA clearance analysis with the new assay was post hoc and done in a small number of patients (40 treated ctDNA-positive patients) and is hypothesis-generating.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.