Does anti-EGFR therapy improve outcome in advanced colorectal cancer? A systematic review and meta-analysis

Cancer Treat Rev. 2012 Oct;38(6):618-25. doi: 10.1016/j.ctrv.2011.11.002. Epub 2011 Nov 26.


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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Cetuximab
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality
  • ErbB Receptors / antagonists & inhibitors*
  • Genes, ras
  • Humans
  • Mutation
  • Randomized Controlled Trials as Topic
  • Treatment Outcome


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Bevacizumab
  • ErbB Receptors
  • Cetuximab