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Background  The epidermal growth factor receptor (EGFR) gene copy number (GCN) has been previously demonstrated to correlate with the clinical outcome of colorectal cancer (CRC) treated with anti-EGFR monoclonal antibodies (mAbs), although it remains controversial. We conducted a systematic review and meta-analysis to assess EGFR GCN as a potential biomarker of survival for patients with advanced CRC receiving treatment with anti-EGFR mAbs.    Methods  We systematically identified articles investigating EGFR GCN by fluorescent or chromogenic  in situ  hybridization or other detection techniques in patients with metastatic CRC treated with panitumumab or cetuximab, (last search: 10 August 2012). Eligible studies had to report on overall survival (OS), progression-free survival (PFS) or time-toprogression (TTP), stratified by EGFR GCN. Summary hazard ratios (HRs) were calculated using random-effects models.    Results  Among 13 identified studies, 10 (776 patients, 302 with increased GCN), 8 (893 patients, 282 with increased GCN) and 3 (149 patients, 66 with increased GCN) were eligible for the OS, PFS and TTP meta-analyses, respectively. Increased EGFR GCN was associated with increased OS (HR = 0.62; 95% CI 0.50–0.77;  P <0.001), PFS (HR = 0.65; 95% CI 0.47–0.89;  P  = 0.008) but not TTP (HR = 0.71; 95% CI 0.44–1.14;  P  = 0.157). It was also shown that EGFR GCN is independent of other factors such as KRAS status. Among those populations received second-line or higher treatment, increased EGFR GCN was strongly associated with improved survival (for OS, HR = 0.60; 95% CI 0.47–0.75; P<0.001; for PFS, HR = 0.59; 95% CI 0.47–0.75; P<0.001), whereas it did not influence survival in patients that received first-line therapy.    Conclusion  Among the anti-EGFR-treated patients, increased EGFR GCN appears to be associated with improved survival outcomes. The effect on survival appears to be related to patients receiving the line of treatment.

plos one

EGFR Gene Copy Number as a Prognostic Marker in Colorectal Cancer Patients Treated with Cetuximab or Panitumumab: A Systematic Review and Meta Analysis