DYNAMIC-III: Circulating Tumour DNA Analysis Informing Adjuvant Chemotherapy in Stage III Colon Cancer - A Multicentre Phase II/III Randomised Controlled Trial

In the adjuvant setting, post-operative circulating tumour DNA (ctDNA) has been shown to be a marker of minimal residual disease, with the presence of ctDNA predicting recurrence in stage II colon cancers and locally advanced rectal cancers.

For patients with stage III colon cancer, adjuvant chemotherapy improves overall survival but some patients will receive adjuvant therapy and still recur, whereas others will not recur in the absence of any adjuvant treatment. For every patient with stage III colon cancer, a reliable biomarker could improve their adjuvant management decision (treatment regimen and/or treatment duration), allowing therapy to be tailored to each patient’s risk of recurrence and moving away from a generic “one size fits all” approach. Specifically, for the great majority of patients, a biomarker that defines a given patient to be either at very high risk (such as a positive ctDNA test) or at very low risk (such as a negative ctDNA test) of recurrence would allow treatment to be escalated in very high risk cases (enhancing the likelihood of preventing disease recurrence and death) or de-escalated for patients with a very low risk of recurrence (reducing treatment related toxicity, reducing direct treatment related cost, and reducing indirect treatment related costs, such as time off work, with minimal to no risk of compromising survival outcome).

The DYNAMIC-III study design incorporates two separate clinical objectives; (i) non-inferiority and (ii) benefit.  The DYNAMIC-III study is a prospective, multi-centre, phase II/III randomised study that aimed to enroll a total of 1000 stage III colon cancer patients. Patients were randomised 1:1 to be treated according to ctDNA results (Arm B: ctDNA-informed), or as per standard of care (Arm A: SOC). Enrolment was stratified by treating centre and clinical risk groups (low risk = T1-3N1; high risk = T4 and/or N2).