Serum matrilysin correlates with poor survival independently of KRAS and BRAF status in refractory advanced colorectal cancer patients treated with irinotecan plus cetuximab

The purpose of the study was to prospectively explore the role of serum MMP-7 as a predictive and prognostic marker of anti-epidermal growth factor receptor (EGFR) therapy and irinotecan efficacy in third-line advanced colorectal cancer therapy. One hundred patients were recruited prospectively from six Spanish hospitals. Patients were treated with biweekly irinotecan 180 mg/m(2) and cetuximab 400 mg/m(2) (loading dose) and weekly cetuximab 250 mg/m(2) until progressive disease or unacceptable toxicity. Baseline MMP-7 was determined using a quantitative solid-phase sandwich ELISA. KRAS and BRAF mutational status were also assessed. The clinical endpoints examined were overall survival (OS), progression-free survival (PFS), and response rate. No association between serum MMP-7 and neither KRAS nor BRAF mutational status was found. The multivariate analysis revealed that MMP-7 predicts PFS both in wild-type (WT) KRAS patients HR 1.03, 95% CI 1.00-1.06; p=0.046) and in mutant KRAS patients (HR 1.18, 95% CI 1.01-1.35; p=0.036). The presence of mutant BRAF was associated with shorter PFS (HR 8.49, 95% CI 2.88-25.0; p<0.001) and worse OS (HR 3.55, 95% CI 1.39-9.09; p=0.008) in the subset of WT KRAS patients. Serum MMP-7 is associated with PFS in colorectal patients treated with anti-EGFR therapy as third-line treatment independently of KRAS status.