In patients with stage II colon cancer where cancer DNA was not present in the blood (as circulating tumor DNA, or ctDNA), adjuvant chemotherapy could be skipped without compromising recurrence-free survival. Conversely, for patients where ctDNA was present after surgery, the rate of recurrence among those who received chemotherapy was low, suggesting a survival benefit from adjuvant chemotherapy, according to results of the phase II DYNAMIC trial presented by Jeanne Tie, MD, and colleague at the 2022 ASCO Annual Meeting (Abstract LBA100).
Jeanne Tie, MD
Circulating tumor DNA can detect micrometastatic disease (also referred to as minimal or measurable residual disease) after surgery, allowing for a more precise prediction of recurrence risk and patient selection for adjuvant therapy. This is the first study to use ctDNA to direct adjuvant therapy in colon cancer.
About the DYNAMIC Trial
In the DYNAMIC trial, 455 patients in Australia and New Zealand were randomly assigned to either ctDNA-guided chemotherapy or standard management, which was clinician-guided based on conventional criteria, including tumor stage of disease, number of lymph nodes assessed, whether the tumor perforated the bowel wall, and other factors.
Median follow-up was 37 months. For ctDNA-guided management, a ctDNA-positive result at either 4 or 7 weeks after surgery led to treatment with oxaliplatin or fluoropyrimidine chemotherapy. Patients with ctDNA-negative results did not receive chemotherapy after surgery.
The primary endpoint was an equivalent or not worse outcome between the two groups assessed by a recurrence-free survival rate at 2 years. A key secondary endpoint was adjuvant use of chemotherapy. All patients were followed every 3 months for 2 years, then every 6 months for 3 years to evaluate for cancer relapse.
The study also included some cases of stage II rectal cancer that had not received chemoradiation prior to surgery. These cancers were generally treated like colon cancers.
Key Findings
Although the current standard of care for stage II colorectal cancer does not involve a ctDNA-directed approach to adjuvant chemotherapy, these results demonstrated similar recurrence-free survival between a ctDNA-guided arm and a standard management arm, despite fewer patients receiving adjuvant chemotherapy.
In the ctDNA-guided arm, patients with a positive ctDNA test result were treated with adjuvant chemotherapy, while those with negative results were not, almost halving the total number of patients who needed to be treated with adjuvant chemotherapy compared to standard management (15.3% vs 27.9%). Of those who received adjuvant chemotherapy, oxaliplatin was given more frequently than fluoropyrimidine for ctDNA-guided patients compared to patients who received standard management (62.2% vs 9.8%).
Patients with a negative ctDNA result, who did not receive adjuvant chemotherapy, had a very low risk of recurrence (7.5%); the risk was even lower in those with negative ctDNA findings who had no clinical risk features (3.3%) or among those with negative ctDNA who had tumors that had grown into the outer lining of the bowel wall but had not grown through it (5.8%).
Patients with a positive ctDNA result, who received adjuvant chemotherapy, had a 3-year recurrence-free survival rate of 86%. Guidance with ctDNA assessment was comparable to standard management for 2-year recurrence-free survival (93.5% vs 92.4%, respectively) and 3-year recurrence-free survival (91.7% vs 92.4%, respectively). Without adjuvant chemotherapy, the 3-year recurrence-free survival for ctDNA-negative patients was 96.7% in the low-risk group and 85.1% in the high-risk group.
“The DYNAMIC study results are very encouraging because previous data suggest that patients with a positive ctDNA score after surgery have a very high recurrence risk if no further treatment is given. Our findings show that with adjuvant treatment, ctDNA-positive patients derive considerable benefit from chemotherapy such as an oxaliplatin-based regimen,” said lead author Jeanne Tie, MD, Associate Professor at the Walter and Eliza Hall Institute of Medical Research and Peter MacCallum Cancer Center, Victoria, Australia.
Next Steps
The trial did not randomly assign the ctDNA-positive and ctDNA-negative patients to treatment vs no treatment, which would have provided more definitive evidence of treatment impact, or lack of impact, in each of the patient subsets. A randomized trial is being considered.
Disclosures: The trial received funding from the National Health and Medical Research Council, the main statutory authority of the Australian government, the Virginia and Ludwig Fund for Cancer Research, the Marcus Foundation, and the U.S. National Institutes of Health. For full disclosures of the study authors, visit coi.asco.org.
