CEA, CA19.9, cDNA and CTC have been reported as useful circulating markers in mCRC pts treated with chemotherapy (CT)-based regimen. We previously reported that CEA kinetic (threshold 0.05) was associated witht outcome [Iwanicki-Caron et al, J Clin Oncol 2008;26:3681-6]. We designed a prospective muticentric trial for CEA kinetic validation and to evaluate CA19.9, cDNA and CTC kinetics.
mCRC pts, PS 0-2, with CEA ≥ 5 µg/L or CA19.9 ≥ 30UI/mL, and who started a CT regimen were included. Plasma were collected taken from baseline (T0) to the fourth cycle for CEA and CA19.9 and at T0 and 6 weeks (W6) for cDNA and CTC kinetics. Cell-free DNA (cfDNA) was quantified by fluorimetric method, circulating tumour DNA (ctDNA) by Digital PCR and CTC (CTC+ vs CTC-) by ScreenCell(R) method. Primary endpoint was 3-months evaluation (control disease (CD) (response/stable) vs progressive disease (PD))) (RECIST 1.1) according to CEA kinetic. Secondary endpoints were progression-free survival (PFS) and overall survival (OS) according to baseline T0 median values (high vs low) of CEA, CA19.9, cfDNA, ctDNA, and CTC +/- and kinetics.
A total of 200 mCRC pts were included with a median follow-up of 12 months (m) (range 1-41). Median CEA, CA19.9, cfDNA and ctDNA were 96 µg/L, 88 UI/mL, 24.2 ng/mL and 15.2% respectively. CtDNA was detected in 90% at T0 from the 95 KRAS/BRAF mutated tumours. A total of 54.7% were CTC+ at T0. CEA kinetic (≤0.05 threshold) was associated with response CD (90 vs 52%, p
This prospective study confirmed that CEA kinetic is clinically relevant to monitor CT in mCRC. Results also highlight that CA19.9, cfDNA and ctDNA are also associated with outcome.
Clinical trial identification
Protocol : 2009/170/HP Clinical trial number : NCT01212510
Legal entity responsible for the study
Amgen, Roche and Merck (pharma) Fondation Pierre Durand et Marie-Therese Chevalier
D. Sefrioui, P. Michel, F. Di Fiore: Industrial partnership with Merck, Amgen and Roche. All other authors have declared no conflicts of interest.