OnCo
trialsTrialPositive

DYNAMIC

Showed that a blood test can safely halve the number of colon cancer patients given chemotherapy after surgery.

ctDNA-guided arm: 15% received chemotherapy vs 28%; 2-year RFS non-inferior (93.5% vs 92.4%). NEJM 2022. DYNAMIC-III (stage III) followed with more nuanced results.

Setting
Stage II colon cancer: ctDNA-guided adjuvant chemotherapy vs standard management
Phase
Phase 2
Sponsor
Walter and Eliza Hall Institute
Headline result
Chemotherapy use 15% vs 28% with non-inferior RFS.
Reported
2022
Enrolled
455
Replication
Supported by observational cohorts (CIRCULATE-Japan GALAXY); DYNAMIC-III in stage III gave a more nuanced result, and randomised escalation trials are ongoing.

Outcomes

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In plain words
What these results mean for people, not percentages
455 people took part
Recurrence-free survival at 2 years (non-inferiority)primarysurrogate endpoint
  • 93.5 vs 92.4 out of 100 alive without the cancer coming back at 2 years with ctDNA-guided management compared with Standard management; 1.1 more per 100.
  • Roughly one extra person helped for every 91 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
  • This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
Patients receiving adjuvant chemotherapyother endpoint
  • 15 vs 28 out of 100 reached this endpoint with ctDNA-guided management compared with Standard management; 13 fewer per 100.
  • On this measure the first group did worse, not better.
  • The p-value (<0.001) says a difference this large would rarely happen by chance; it does not say how large or how useful the difference is.
  • This endpoint is not one of the standard survival or response measures; read it alongside the trial's primary result.
Be careful
  • These results apply to the people the trial enrolled: Stage II colon cancer: ctDNA-guided adjuvant chemotherapy vs standard management. People in a different situation may not see the same effect.

Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.

455 participants enrolled.

Recurrence-free survival at 2 years (non-inferiority)primary
ctDNA-guided management93.5 of 100
n = 302
Standard management92.4 of 100
n = 153

Non-inferiority met (margin −8.5 points)

Source
Patients receiving adjuvant chemotherapy
· p <0.001
ctDNA-guided management15 of 100
Standard management28 of 100
Source
EndpointArmnValueHR (95% CI)pSource
Recurrence-free survival at 2 years (non-inferiority)primaryctDNA-guided management30293.5%——link
Standard management15392.4%
Patients receiving adjuvant chemotherapyctDNA-guided management—15%—<0.001link
Standard management—28%
Replication
Supported by observational cohorts (CIRCULATE-Japan GALAXY); DYNAMIC-III in stage III gave a more nuanced result, and randomised escalation trials are ongoing.

Key papers

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rctNew England Journal of Medicine 2022changed practice
DYNAMIC: a blood test safely halved chemotherapy use after surgery for stage II colon cancer

For stage II colon cancer, where most patients are cured by surgery alone, a blood test can identify the minority who benefit from chemotherapy and spare everyone else its side effects. It does not yet prove that treating ctDNA-positive patients improves survival compared with not treating them.

Connected

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cancers

1
Colorectal cancer

technologies

1
MRD / molecular residual disease testing

institutions

1
Australasian Gastro-Intestinal Trials Group

pathways

1
Clonal evolution & minimal residual disease

terms

3
ColectomyDe-escalation, escalation and response-adapted therapyMinimal / molecular residual disease (MRD)

trials

1
CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)

pairings

1
ctDNA MRD → adjuvant therapy decision

ideas

6
A national platform trial that every ctDNA-positive patient can joinA national residual-disease weather service: serial blood tests for every curatively treated patient, pooledctDNA-guided adjuvant therapy as the default in stage II-III colon cancerFormally qualify tumour-DNA blood tests as a surrogate endpoint for adjuvant trialsStrip the platelet coat off travelling tumour cells in ctDNA-positive patientsUse tumour DNA in blood to decide when to pause treatment in metastatic cancer

bottlenecks

2
Dormant cells and minimal residual diseaseMetastasis is understood least and studied last

key papers

1
DYNAMIC: a blood test safely halved chemotherapy use after surgery for stage II colon cancer