Dr. Morris on the Investigation of the Role of ctDNA in Stage II CRC

Van K. Morris, MD, an associate professor in the Department of Gastrointestinal (GI) Medical Oncology of the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discusses the evaluation of circulating tumor (ctDNA) as a predictive biomarker for the use of adjuvant chemotherapy in patients with low-risk, stage II colon cancer.

The ongoing phase 2/3 NRG-GI005 (COBRA) study (NCT04068103) is evaluating the use of ctDNA in this patient population as a predictive biomarker to identify patients who may or may not benefit from chemotherapy following surgery. After undergoing surgery, patients in arm A will undergo active surveillance, and blood drawn at baseline will be stored and later tested for ctDNA. Those in arm B will have blood drawn following surgery, and it will be tested at baseline to determine ctDNA status. Those who are ctDNA negative will undergo surveillance, and those who are ctDNA positive will receive adjuvant chemotherapy.

The co-primary end points of the trial are the clearance of ctDNA to undetectable levels for those who have ctDNA detected at baseline, as well as recurrence-free survival (RFS) for patients who are ctDNA positive at baseline. Secondary outcomes included RFS in the overall population, overall survival, and time to recurrence.

ctDNA is a powerful and useful tool across the oncology landscape, and detectable ctDNA after the completion of definitive therapies or surgery is highly prognostic for the chance that a patient’s cancer could return, Morris says. Conversely, patient with undetectable ctDNA, are less likely to recur, Morris adds.

However, investigators are still aiming to collect strong, prospective evidence on the use of ctDNA to guide clinicians and patients regarding treatment decisions that could help improve outcomes. Along with investigating ctDNA clearance rates in patients with ctDNA positivity, investigators hope to better understand how this correlates with survival outcomes, Morris concludes.