The clinical application of post-operative ctDNA testing in low-risk stage IIA colon cancer remains unclear

The NRG-GI005 (COBRA) study was a prospective, randomized, phase II/III trial designed to evaluate ctDNA clearance rate as a primary endpoint for guiding adjuvant chemotherapy in patients with stage IIA colon cancer. The study included 635 patients who underwent surgical resection but had no traditional high-risk features. Patients were randomly assigned to two arms. In Arm A, patients were assigned to standard care, meaning they underwent close observation without chemotherapy. In Arm B, patients received ctDNA assay-directed therapy: If their ctDNA test was negative, they continued close observation. If their ctDNA test was positive, they received 6 months of adjuvant chemotherapy (CAPOX or FOLFOX). The primary endpoint of the study was ctDNA clearance rate at 6 months. The researchers compared the ctDNA clearance rates between the first 16 patients with positive ctDNA tests in Arm A and Arm B. If the p-value was greater than 0.35 (p > 0.35), the study would be stopped for futility and would not proceed to the phase III portion.

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Among the 16 patients with positive ctDNA tests, 3 out of 7 patients (43%) in Arm A and 1 out of 9 patients (11%) in Arm B had ctDNA clearance at 6 months (p = 0.98). Based on the pre-specified stopping rule, the study was terminated. The results of this study suggest that ctDNA testing after surgery does not improve ctDNA clearance rates when used to guide adjuvant chemotherapy in patients with low-risk stage IIA colon cancer. The NRG-GI005 study is the largest study to date to evaluate the role of ctDNA in guiding colon cancer treatment. The results suggest that the clinical application of ctDNA testing after surgery in low-risk stage IIA colon cancer remains unclear. Further research is needed to explore the potential applications of ctDNA testing in other cancer patients. For example, ctDNA testing may be more helpful in high-risk colon cancer patients or patients with other cancers.

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Reference: 

Morris VK, Yothers G, Kopetz S, et al. Phase II results of circulating tumor DNA as a predictive biomarker in adjuvant chemotherapy in patients with stage II colon cancer: NRG-GI005 (COBRA) phase II/III study. J Clin Oncol. 2024;42(suppl 3):5.