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

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. (C) 2011 Elsevier Ltd. All rights reserved.