title: Cetuximab/irinotecan-chemotherapy in KRAS wild-type pretreated metastatic colorectal cancer: a pooled analysis and review of literature.
abstract: BACKGROUND
  Cetuximab and irinotecan are effective agents in advanced colorectal cancer (CRC) after either irinotecanor oxaliplatin-based first-line chemotherapy. Here, the efficacy of this combination in patients with the KRAS wild-type gene as second- or further-line therapy is reviewed and data are collected in a pooled analysis.
  
  
  METHODS
  Studies that enrolled pretreated CRC patients for second-line therapy or beyond were identified using electronic databases (PubMed and EMBASE). A systematic analysis was conducted using Comprehensive Meta Analysis (version 2.2.064) to calculate the event rate of response and the 95% confidence interval. The weighted median overall survival (OS) and progression-free survival (PFS) were also calculated with NCSS 2007 software. We tested for significant heterogeneity using Cochran's chi-square test and the I(2) index.
  
  
  RESULTS
  Twenty-five studies published between 2007 and 2012 were eligible for this analysis, with a total of 1,712 KRAS wild-type patients enrolled. The overall response rate was 31.9% with similar response rates of 28. 7% for second-line treatment and 31.1% for third or further lines. The overall weighted median OS and PFS were 12.5 and 6 months with a weighted OS of 11.56 and 12.2 months for second- and further-line CRC settings, respectively.
  
  
  CONCLUSIONS
  In metastatic KRAS wild-type CRC patients pretreated with one or more lines of therapy, cetuximab plus irinotecan-based chemotherapy is an active treatment. Response rates and survival outcomes appear similar in second-line therapy or beyond.
authors.affiliation: Medical Oncology Unit, Oncology Department, Azienda Ospedaliera Treviglio-Caravaggio, Piazzale Ospedale 1, 24047 Treviglio (BG), Italia. faupe@libero.it.
authors.forename: Sandro
authors.initials: S
authors.lastname: Barni
authors.forename: Mara
authors.initials: M
authors.lastname: Ghilardi
authors.forename: Karen
authors.initials: K
authors.lastname: Borgonovo
authors.forename: Mary
authors.initials: M
authors.lastname: Cabiddu
authors.forename: Alberto
authors.initials: A
authors.lastname: Zaniboni
authors.forename: Fausto
authors.initials: F
authors.lastname: Petrelli
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D004273:DNA, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D000077146:Irinotecan; D009154:Mutation; D009362:Neoplasm Metastasis; D011355:Prodrugs; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D004273:DNA, Neoplasm; C117307:KRAS protein, human; D011355:Prodrugs; D011518:Proto-Oncogene Proteins; D000077146:Irinotecan; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D002166:Camptothecin