title: Serum matrilysin correlates with poor survival independently of KRAS and BRAF status in refractory advanced colorectal cancer patients treated with irinotecan plus cetuximab.
abstract: 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.
authors.affiliation: Medical Oncology Department, Institut Clínic Malalties Hemato-Oncológiques (ICMHO), Hospital Clínic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERehd, Villarroel 170, 08036 Barcelona, Spain.
authors.forename: Xabier
authors.initials: X
authors.lastname: Garcia-Albeniz
authors.forename: Carles
authors.initials: C
authors.lastname: Pericay
authors.forename: Virginia
authors.initials: V
authors.lastname: Alonso-Espinaco
authors.forename: Vicente
authors.initials: V
authors.lastname: Alonso
authors.forename: Pilar
authors.initials: P
authors.lastname: Escudero
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernández-Martos
authors.forename: Rosa
authors.initials: R
authors.lastname: Gallego
authors.forename: Pere
authors.initials: P
authors.lastname: Gascón
authors.forename: Sergi
authors.initials: S
authors.lastname: Castellví-Bel
authors.forename: Joan
authors.initials: J
authors.lastname: Maurel
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality*; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000097:blood*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011237:Predictive Value of Tests; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D000077146:Irinotecan; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020783:Matrix Metalloproteinase 7; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D002166:Camptothecin