Circulating tumor DNA (ctDNA) assessment can reduce the use of adjuvant chemotherapy in Stage II colon cancer without compromising recurrence-free survival (RFS). The low recurrence rate in ctDNA-positive patients who received chemotherapy suggests a survival benefit from adjuvant therapy, while ctDNA-negative patients are unlikely to benefit from chemotherapy.
A ctDNA-guided strategy almost halved the number of colon cancer patients who received chemotherapy post-surgery (15% vs. 28%) and yielded comparable cancer-free survival at 3 years.
Surgery alone can cure the majority (more than 80%) of Stage II colon cancers. The benefit of chemotherapy after surgery is unclear and recommended for patients with risk features in the tumor tissue. However, fewer than 5 in 100 patients will benefit.
"More precise prediction of relapse risk can help limit treatment to very high-risk patients who are most likely to benefit and avoid unnecessary treatment in low-risk patients who are unlikely to benefit," said lead author Jeanne Tie, MD, Associate Professor at the Walter and Eliza Hall Institute of Medical Research and Peter MacCallum Cancer Centre in Victoria, Australia. She presented the results of the study (Abstract LBA100) at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting. The results were also published in the New England Journal of Medicine (2022; doi: 10.1056/NEJMoa2200075).
The DYNAMIC study was designed to show that using a ctDNA blood test to direct post-surgical therapy in Stage II colon cancer can reduce the use of chemotherapy without impacting the risk of relapse.
"Our findings show that, with adjuvant treatment, ctDNA-positive patients derive considerable benefit from chemotherapy, such as an oxaliplatin-based regimen," Tie noted.
About the Study
The Phase II DYNAMIC trial included 455 patients, median age 64 years, in Australia and New Zealand who 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.
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 an RFS rate at 2 years. A key secondary endpoint was post-surgical use of chemotherapy. All patients were followed every 3 months for 2 years, then every 6 months for 2 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
After a median follow-up of 37 months, "the outcomes show for patients with a ctDNA-positive result [that] the chance of being alive and cancer-free is 86.4 percent after treatment with chemotherapy. For patients with a ctDNA-negative result, the chance of being alive and cancer-free is 92.5 percent without chemotherapy," said Tie.
In the ctDNA-guided arm, patients with a positive ctDNA test result were treated with adjuvant chemotherapy, while those with negative results were not. Of those who received post-surgical chemotherapy, oxaliplatin was given more frequently than fluoropyrimidine for ctDNA-guided patients compared to standard management patients (62.2% vs. 9.8%).
Patients with a negative ctDNA result had a very low risk of recurrence (7.5%); the risk was even lower in negative ctDNA patients without any clinical risk features (3.3%) or among those negative ctDNA patients with tumors that had grown into the outer lining of the bowel wall, but had not grown through it (5.8%).
Guidance with ctDNA assessment was comparable to standard management for 2-year RFS (93.5% vs. 92.4%, respectively) and 3-year RFS (91.7% vs. 92.4%, respectively). Without post-surgical chemotherapy, the 3-year RFS for ctDNA-negative patients was 96.7 percent in the low-risk group and 85.1 percent in the high-risk group.
Tie concluded: "In Stage II colon cancer, ctDNA assessment after surgery allows a more precise prediction of relapse and patient selection for post-surgical therapy. The ctDNA-guided approach can reduce the number of patients treated with chemotherapy. Given the favorable outcome in ctDNA-positive patients treated with chemotherapy, this high-risk subgroup of patients likely derived substantial benefit from treatment."
She added: "Patients with a negative ctDNA result have a very low risk of relapse despite not receiving chemotherapy, suggesting post-surgery therapy is unlikely to benefit this group of patients."
The trial did not randomize the ctDNA-positive and ctDNA-negative patients to treatment versus 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.
ASCO Expert Cathy Eng, MD, Professor of Medicine (Hematology and Oncology) at the Vanderbilt-Ingram Cancer Center, commented: "Liquid biopsies can be a useful tool for guiding treatment decisions. Thanks to the results of this study, we may now be able to use it to better identify which patients with Stage II colon cancer would benefit from post-surgery treatment with chemotherapy and which ones can be spared the additional treatment without compromising RFS."
Mark L. Fuerst is a contributing writer.