Abstract
BackgroundWe aim to test the hypothesis that high plasma YKL-40 is associated with short progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer (mCRC) treated with first-line oxaliplatin and 5-flourouracil with or without cetuximab.Patients and MethodsA total of 566 patients in the NORDIC VII Study were randomized 1∶1∶1 to arm A (Nordic FLOX), arm B (Nordic FLOX + cetuximab), or arm C (Nordic FLOX + cetuximab for 16 weeks followed by cetuximab alone as maintenance therapy). Pretreatment plasma samples were available from 510 patients. Plasma YKL-40 was determined by ELISA and dichotomized according to the age-corrected 95% YKL-40 level in 3130 healthy subjects.ResultsPretreatment plasma YKL-40 was elevated in 204 patients (40%), and median YKL-40 was higher in patients with mCRC than in healthy subjects (age adjusted, P<0.001). Patients with elevated YKL-40 had shorter PFS than patients with normal YKL-40 (7.5 vs. 8.2 months; hazard ratio (HR) = 1.27 95% confidence interval (CI) 1.05–1.53 P = 0.013) and shorter OS (16.8 vs. 23.9 months; HR = 1.33, 1.04–1.69, P = 0.024). Multivariate Cox analysis demonstrated that elevated pretreatment YKL-40 was an independent biomarker of short OS (HR = 1.12, 1.01–1.25, P = 0.033). The ratio of the updated plasma YKL-40 (i.e. level after 1, 2, 8 weeks of treatment, and at end of treatment compared to the baseline level) was associated with OS (HR = 1.27, 1.06–1.52, P = 0.011).ConclusionsPlasma YKL-40 is an independent prognostic biomarker in patients with mCRC treated with first-line oxaliplatin-based therapy alone or combined with cetuximab.
Highlights
Research into biological markers hopes to provide the clinician with an opportunity to choose the best treatment for the individual patient
Pretreatment plasma YKL-40 was elevated in 204 patients (40%), and median YKL-40 was higher in patients with metastatic colorectal cancer (mCRC) than in healthy subjects
Patients with elevated YKL-40 had shorter progression-free survival (PFS) than patients with normal YKL-40 (7.5 vs. 8.2 months; hazard ratio (HR) = 1.27 95% confidence interval (CI) 1.05–1.53 P = 0.013) and shorter overall survival (OS) (16.8 vs. 23.9 months; HR = 1.33, 1.04–1.69, P = 0.024)
Summary
Research into biological markers hopes to provide the clinician with an opportunity to choose the best treatment for the individual patient. Several clinical and laboratory values give prognostic information regarding treatment strategy for patients with metastatic colorectal cancer (mCRC). KRAS status is presently the only biomarker routinely used to select patients with mCRC for epidermal growth factor receptor (EGFR) inhibition-targeted therapy. Patients with wild type (wt) KRAS mCRC benefit from inhibition in combination with FOLFIRI or FOLFOX [1,2,3], even though the effect is not confirmed in all phase III studies, where EGFR-inhibitors were combined with some oxaliplatin-based regimes [4,5]. We aim to test the hypothesis that high plasma YKL-40 is associated with short progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer (mCRC) treated with first-line oxaliplatin and 5flourouracil with or without cetuximab
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