Can ctDNA-directed therapy improve outcomes in low-risk colon cancer?

In a low-risk population of patients with stage II colon cancer, treating ctDNA-positive patients with adjuvant chemotherapy for 6 months did not lead to an improvement in ctDNA clearance, results of a phase 2 study showed.

In the phase 2 NRG-GI005/COBRA study (NCT04068103), 635 patients with resected stage IIA colon cancer were randomised 1:1 to standard-of-care active surveillance (arm 1) or to assay-directed therapy (arm 2). In the latter arm, participants with detected ctDNA were treated with mFOLFOX6 or CAPOX chemotherapy for 6 months. Dr Van Morris (MD Anderson Cancer Center, TX, USA) presented the findings [1].

In total, ctDNA positivity was detected in 33 patients. The current analysis included 16 of them: 7 had been randomised to arm 1 and 9 had been randomised to arm 2. The ctDNA clearance rate was 43% in arm 1 and 11% in arm 2 (one-sided P=0.98). “Since the one-sided P-value exceeded 0.35, the null hypothesis could not be rejected and we had to stop the trial due to futility,” said Dr Morris.

Despite the neutral trial results, Dr Morris pleaded for more ctDNA trials: “Prospective trials assessing ctDNA as a surrogate for minimal residual disease are feasible and necessary in order to confirm clinically relevant hypotheses in oncology,” he reasoned. “Future clinical trial design should account for the evolution of ctDNA methodologies and assay performance, in order to answer relevant questions in the field.”

1. Morris VK, 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. Abstract 6, ASCO Gastrointestinal Cancers Symposium 2024, 18–20 January, San Francisco, CA, USA.

 

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Posted on 13 February, 202428 March, 2024