Abstract
BackgroundThe 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.MethodsWe 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.ResultsAmong 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.ConclusionAmong 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.
Highlights
The major prognostic determinant for patients with non-resectable metastic colorectal cancer (CRC) is the response to systemic therapy [1]
Identification and Eligibility of Relevant Studies We performed a systematic computerized search of the MEDLINE (PubMed) database, EMbase and the Cochrane library to identify all published articles related to the identification of mutations in epidermal growth factor receptor (EGFR) pertaining to CRC, using the algorithm: AND AND
Eligible studies included in the meta-analysis had to meet the following criteria: (a) a cohort colorectal cancer study; (b) hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) comparing overall survival (OS), progression-free survival (PFS) or time-to-progression (TTP) stratified by EGFR gene copy number for patients receiving mono- or combination therapy with either cetuximab or panitumumab were reported or allowed the calculation; and (c) written in English
Summary
The major prognostic determinant for patients with non-resectable metastic colorectal cancer (CRC) is the response to systemic therapy [1]. During these last years, novel strategies that target the epidermal growth factor receptor (EGFR) have been evaluated in CRC, including monoclonal antibodies (mAbs). Novel strategies that target the epidermal growth factor receptor (EGFR) have been evaluated in CRC, including monoclonal antibodies (mAbs) These mAbs interfering with the extracellular domain of EGFR, were designed to be used when other treatments failed [2]. 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
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