Monitoring levels of circulating cell‐free DNA in patients with metastatic colorectal cancer as a potential biomarker of responses to regorafenib treatment

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Pastor, Brice | Thierry, André | Henriques, Julie | Trouilloud, Isabelle | Tournigand, Christophe | Marine, Jary | Mazard, Thibault | Louvet, Christophe | Azan, Simon | Bauer, Audrey | Roch, Benoit | Sanchez, Cynthia | Vernerey, Dewi | Thierry, Alain, R | Adenis, Antoine

Edité par CCSD ; FEBS Press -

International audience. Circulating cell-free DNA (cfDNA) contains circulating tumor DNA (ctDNA), which can be obtained from serial liquid biopsies to enable tumor genome analysis throughout the course of treatment. We investigated cfDNA and mutant ctDNA as potential biomarkers to predict the best outcomes of regorafenib-treated metastatic colorectal cancer (mCRC) patients. We analyzed longitudinally collected plasma cfDNA of 43 mCRC patients prospectively enrolled in the phase II TEXCAN trial by IntPlex qPCR. Qualitative (KRAS, NRAS, BRAFV600E mutations) and quantitative (total cfDNA concentration, mutant ctDNA concentration, mutant ctDNA fraction) parameters were correlated with overall survival (OS) and progression-free survival (PFS). When examined as classes or continuous variables, the concentrations of total cfDNA, mutant ctDNA, and partly, mutant ctDNA fraction prior to regorafenib treatment correlated with OS. Patients with baseline-cfDNA >26 ng/mL had shorter OS than those with cfDNA value below this threshold (4.0 vs 6.9 months; logrank P=0.0366). Patients with baseline mutant ctDNA >2 ng/mL had shorter OS than those with mutant ctDNA below this threshold (logrank P=0.0154). We show that pre-treatment cfDNA and mutant ctDNA levels may identify mCRC patients that may benefit from regorafenib treatment.

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