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

Claire L. Vale, Jayne F. Tierney, David Fisher, Richard A. Adams, Richard Kaplan, Timothy S. Maughan, Mahesh K.B. Parmar, Angela M. Meade

Research output: Contribution to journalReview articlepeer-review

90 Scopus citations

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.

Original languageEnglish
Pages (from-to)618-625
Number of pages8
JournalCancer Treatment Reviews
Volume38
Issue number6
DOIs
StatePublished - Oct 2012
Externally publishedYes

Keywords

  • Anti-EGFR therapy
  • Colorectal cancer
  • Meta-analysis
  • Systematic review

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