title: Does anti-EGFR therapy improve outcome in advanced colorectal cancer? A systematic review and meta-analysis.
abstract: BACKGROUND
  Randomised controlled trials (RCTs) of anti-EGFR monoclonal antibodies (MAb) in patients with advanced colorectal cancer (aCRC) have reported conflicting results.
  
  
  METHODS
  A systematic review of RCTs comparing standard treatments±anti-EGFR MAbs was conducted. Hazard ratios (HR) for progression-free (PFS) and overall survival (OS) were derived for patients with wild-type (WT) and mutant KRAS. Prespecified analyses were conducted for line of treatment, MAb used, chemotherapy regimen, and choice of fluouropyrimidine. Trials using bevacizumab on both arms were included in a sensitivity analysis.
  
  
  RESULTS
  Fourteen eligible RCTs were identified, with results by KRAS status available for ten RCTs. For third line treatment, the effect of anti-EGFR MAbs depended on KRAS status (interaction p<0.00001), with a PFS benefit for patients with WT KRAS only (HR=0.43, 95% CI 0.35-0.52, p<0.00001). For first and second line treatment, the effect also appeared to depend on KRAS status (interaction p=0.0003), again with the PFS benefit only for patients with WT KRAS (HR=0.83, 95% CI 0.76-0.90, p<0.0001). Differences between trial results (heterogeneity p=0.02, I(2)=62%) were best explained by the fluouropyrimidine used, with PFS benefits confined to trials combining MAbs alongside 5FU-based chemotherapy (HR=0.77, 95% CI 0.70-0.85, p<0.00001). There was no evidence of a PFS benefit when MAbs were given with bevacizumab.
  
  
  CONCLUSIONS
  For aCRC patients with WT KRAS, there are clear benefits of anti-EGFR MAbs in the third line and in the first and second line, when used alongside infusional 5FU-based regimens. However, there is no benefit for patients with KRAS mutations.
authors: Medical Research Council Clinical Trials Unit, Aviation House, 125 Kingsway, London WC2B 6NH, UK. cv@ctu.mrc.ac.uk
authors: Claire L
authors: CL
authors: Vale
authors: Jayne F
authors: JF
authors: Tierney
authors: David
authors: D
authors: Fisher
authors: Richard A
authors: RA
authors: Adams
authors: Richard
authors: R
authors: Kaplan
authors: Timothy S
authors: TS
authors: Maughan
authors: Mahesh K B
authors: MK
authors: Parmar
authors: Angela M
authors: AM
authors: Meade
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D011905:Genes, ras; D006801:Humans; D009154:Mutation; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068258:Bevacizumab; D066246:ErbB Receptors; D000068818:Cetuximab