Plasma concentrations of YKL-40 in chemo-naive patients with metastatic colorectal cancer treated with FLOX with or without cetuximab: Results from the NORDIC VII study.

Abstract

3548 Background: KRAS status is presently the best biomarker to select patients with metastatic colorectal cancer (mCRC) for therapy with EGFR inhibition even though not confirmed in all phase III studies. In the NORDIC VII study a survival benefit of adding cetuximab to the Nordic FLOX regimen could not be confirmed. Identification of new predictive and prognostic biomarkers is essential. Plasma concentration of YKL-40 is emerging as a new biomarker in patients with cancer and inflammatory diseases. We tested the hypothesis that high plasma YKL-40 associates with short progression free survival (PFS) and short overall survival (OS) in patients included in the NORDIC VII Study. Methods: 566 patients with mCRC were randomized to: A) Nordic FLOX; B) FLOX + cetuximab; and C) FLOX for 16 weeks + cetuximab continuously. Plasma samples were available from 510 patients (90%). Pretreatment plasma YKL-40 was determined by ELISA (Quidel), and the plasma YKL-40 concentration was dichotomized according to the age-corrected 95% YKL-40 level in 3130 healthy subjects. Results: Plasma YKL-40 was elevated in 204 patients (40%) and the median plasma YKL-40 was higher in the study group compared to healthy subjects (120 mg/l vs. 40 mg/l, p<0.001). Elevated plasma YKL-40 was associated with short PFS (HR=1.25, 95% CI 1.04-1.51, p=0.02). This relationship was demonstrated only in patients treated with FLOX chemotherapy alone (HR=1.42, 1.02-1.98, p=0.04). High plasma YKL-40 was associated with short OS in all patients (HR=1.55, 1.25-1.92, p<0.001) and in the different treatment groups (A: HR=1.54, 1.05-2.26, p=0.03; B: HR=1.40, 0.97-2.01, p=0.07; C: 1.79, 1.23-2.60, p=0.002). Multivariate analysis (YKL-40, performance status, number of metastatic sites) demonstrated that elevated plasma YKL-40 was an independent biomarker of short OS (HR=1.46, 1.17-1.81, p=0.001). Conclusions: Plasma YKL-40 may be a new prognostic biomarker in patients with mCRC treated with 1st line FLOX chemotherapy, with or without cetuximab. The predictive value of plasma YKL-40 is not yet clarified.