ctDNA variations according to treatment intensity in first-line metastatic colorectal cancer

Abstract

Circulating tumor DNA variations (∆ctDNA) were reported to be associated with treatment efficacy in metastatic colorectal cancer (mCRC). The present study evaluated ∆ctDNA according to first-line treatment intensity. Patients from two prospective ctDNA collections were divided into Group ≤ 2 drugs and Group ≥ 3 drugs. ∆ctDNA were analysed from baseline to cycle 3 or 4 (C3-4) according to three predefined subgroups: ∆ctDNA ≥ 80%_ undetectable, ∆ctDNA ≥ 80%_ detectable, and ∆ctDNA < 80%. Impact of ∆ctDNA on progression-free survival (PFS) and overall survival (OS) were analysed. Pretreatment ctDNA was detected in 129/152 (84.9%) of patients. A ∆ctDNA ≥ 80%_undetectable was more frequent in Group ≥ 3 than ≤ 2 drugs (respectively 51.5% vs. 32.7%, p = 0.015). Patients with ∆ctDNA ≥ 80%_undetectable had longer survival than other ∆ctDNA subgroups, in Group ≥ 3 drugs (mPFS 11.5 vs 7.8 vs 6.3 months, p = 0.02: mOS 30.2 vs 18.1 vs 16.4 month, p = 0.04) and in Group ≤ 2 drugs (mPFS 8.4 vs 6.0 vs 5.3 months, p = 0.05; mOS 29.6 vs 14.6 vs 14.6 months, p = 0.007). Early ∆ctDNA are associated to treatment intensity in first line mCRC with a significant impact on prognosis.