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Skin toxicity is a known clinical signature used to predict the prognosis of anti‐epidermal growth factor receptor ( EGFR ) antibody treatment in metastatic colorectal cancer ( mCRC ). There are no biological markers to predict skin toxicity before anti‐ EGFR  antibody treatment in  mCRC  patients. Between August 2008 and August 2011, pretreatment serum samples were obtained from   KRAS   wild‐type ( WT ) patients who received anti‐ EGFR  antibody treatment. Serum levels of ligands were measured by  ELISA . A total of 103   KRAS    WT  patients were enrolled in the study. Progression‐free survival and overall survival of patients with a high grade (grade 2–3) of skin toxicity were significantly longer than those with a low grade (grade 0–1) of skin toxicity (median progression‐free survival, 6.4 months  vs  2.4 months,  P  < 0.001; median overall survival, 14.6 months  vs  7.1 months,  P  = 0.006). There were significant differences in distribution of serum levels of epiregulin ( EREG ), amphiregulin ( AREG ), and hepatocyte growth factor ( HGF ) between groups of low/high grade of skin toxicity ( P  < 0.048,  P  < 0.012,  P  < 0.012, respectively). In addition, serum levels of  HGF ,  EREG , and  AREG  were inversely proportional to grades of skin toxicity as determined by the Cochran–Armitage test ( P  = 0.019,  P  = 0.047,  P  = 0.021, respectively). Our study indicated that serum levels such as  HGF ,  EREG , and  AREG  may be significant markers to predict the grade of skin toxicity and the prognosis of anti‐ EGFR  antibody treatment, which contribute to improvement of the management of skin toxicity and survival time in  mCRC  patients.

Association between serum ligands and the skin toxicity of anti‐epidermal growth factor receptor antibody in metastatic colorectal cancer