Abstract 3255
Background
YKL-40 (CHI3L1) plays a major role in inflammation and angiogenesis. In patients with metastatic colorectal cancer (mCRC) we wanted to test if high pretreatment levels of plasma YKL-40 and change of YKL-40 during therapy with cetuximab and irinotecan was independent of KRAS mutation status and associated with progression free (PFS) and overall survival (OS).
Methods
Two independent studies of 162 patients and 98 patients (Study I and II) with mCRC resistant to 5-FU, oxaliplatin and irinotecan treated with cetuximab and irinotecan without knowledge of their KRAS mutation status were performed in Denmark between 2006 and 2008. Plasma YKL-40 was determined by ELISA. Seven mutations in the KRAS oncogene were determined by the DxS TheraScreen kit.
Results
In both studies a high pretreatment plasmaYKL-40 (log transformed continuous variable) was significantly associated to short overall survival (OS) independent of KRAS mutation status (Study I: HR = 1.17, 95% CI 1.04-1.30, P = 0.009; interaction between KRAS and YKL-40 P = 0.75; Study II: HR = 1.34, 95% CI 1.12-1.59, P = 0.0001; interaction between KRAS and YKL-40 p = 0.85). Multivariate Cox analysis including YKL-40, age, sex, performance status (PS), number of metastatic sites and KRAS mutation status demonstrated that elevated pretreatment plasma YKL-40 was an independent biomarker of OS (Study I: HR = 1.53, 95% CI 1.10-2.13, P = 0.013; Study II: HR = 2.89, 1.84-4.53, P
Conclusions
In two independent studies plasma YKL-40 before and during treatment of patients with mCRC with cetuximab and irinotecan was a strong independent biomarker of PFS and OS independent of KRAS mutation status.
Clinical trial identification
EudraCT number 2006-001-961-40
Legal entity responsible for the study
Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen
Funding
Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen
Disclosure
All authors have declared no conflicts of interest.