In patients with stage II colon cancer, for which cancer DNA was not present in the blood (circulating tumour DNA, or ctDNA) post-surgical 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 post-surgical chemotherapy, according to new research to be presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.

While the current standard of care for stage II colorectal cancer does not involve a ctDNA-directed approach to post-surgical chemotherapy, the randomized phase II DYNAMIC trial results demonstrated similar recurrence-free survival between a ctDNA-guided arm and a standard management arm, despite fewer patients receiving post-surgical 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 post-surgical chemotherapy compared to standard management (15.3% vs. 27.9%).

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, who did not receive post-surgical chemotherapy, 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 tumours 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 post-surgical chemotherapy, had a three-year recurrence-free survival rate of 86%.

Guidance with ctDNA assessment was comparable to standard management for two-year recurrence-free survival (93.5% vs. 92.4%, respectively) and three-year recurrence-free survival (91.7% vs. 92.4%, respectively).

Without post-surgical chemotherapy, the three-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, who is an Associate Professor at the Walter and Eliza Hall Institute of Medical Research and Peter MacCallum Cancer Center, Victoria, Australia.

About 151,030 new colorectal cancer cases are expected to be diagnosed in the United States (U.S.) in 2022.

An estimated 52,580 deaths will occur due to the disease.

Circulating tumour DNA can detect micro-metastatic disease (also referred to as minimal residual disease) after surgery, allowing for a more precise prediction of recurrence risk and patient selection for post-surgical therapy.

This is the first study to use ctDNA to direct post-surgical therapy in colon cancer.

In the phase II 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: tumour stage of disease, number of lymph nodes assessed, whether the tumour perforated the bowel wall and other factors.

Median follow-up was 37 months.

For ctDNA-guided management, a ctDNA-positive result at either four or seven 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 two years.

A key secondary endpoint was post-surgical use of chemotherapy.

All patients were followed every three months for two years, then every six months for three 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.

The trial did not randomize the ctDNA-positive and -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 randomised trial is being considered.

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.

“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 patient with stage II colon cancer would benefit from post-surgery treatment with chemotherapy and which ones can be spared the additional treatment, without compromising relapse-free survival,” said ASCO Expert Cathy Eng, MD, FACP, FASCO.   

Source: ASCO

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