<it>EGFR</it> gene copy number as a predictive biomarker for the treatment of metastatic colorectal cancer with anti-EGFR monoclonal antibodies: a meta-analysis

• Main Authors: Yang Zu-Yao, Shen Wei-Xi, Hu Xue-Feng, Zheng Da-Yong, Wu Xin-Yin, Huang Ya-Fang, Chen Jin-Zhang, Mao Chen, Tang Jin-Ling
• Format: Article
• Language: English
• Published: BMC 2012-08-01
• Series: Journal of Hematology & Oncology
• Subjects: Colorectal neoplasms; Monoclonal antibodies; Cetuximab; Panitumumab; Epidermal growth factor receptor; Systematic review; Meta-analysis
• Online Access: http://www.jhoonline.org/content/5/1/52

<p>Abstract</p> <p>Background</p> <p>Epidermal growth factor receptor gene copy number (<it>EGFR</it> GCN) has been heavily investigated as a potential predictive biomarker for the treatment of metastatic colorectal cancer (mCRC) with anti-EGFR monoclonal antibodies (MAbs). The objective of this study was to systematically review current evidences on this issue.</p> <p>Methods</p> <p>PubMed, EMBASE, The Cochrane Library, Chinese Biomedical Literature Database, Wanfang Data, and the conference abstracts of American Society of Clinical Oncology and European Society of Medical Oncology were comprehensively searched. Studies that reported the objective response rate (ORR), progression-free survival, and/or overall survival of mCRC patients treated with anti-EGFR MAbs, stratified by <it>EGFR</it> GCN status, were included. The effect measures for binary outcome (response) and time-to-event outcomes (progression-free survival and overall survival) were risk difference and hazard ratio, respectively. Statistical heterogeneity among the studies was assessed by the Cochran’s <it>Q</it>-test and the <it>I</it>² statistic. If appropriate, a quantitative synthesis of data from different studies would be conducted with a random-effects model.</p> <p>Results</p> <p>Nineteen eligible studies were identified. The criteria for increased <it>EGFR</it> GCN (GCN+) were highly inconsistent across different studies. The prevalence of GCN + ranged from 6.9% to 88.9%, and the difference in ORR between patients with GCN + and those with non-increased <it>EGFR</it> GCN (GCN-) varied from −28% to 84%. Because of the significant heterogeneity, no quantitative synthesis of data was performed. There was a general trend towards higher ORR in patients with GCN+. The difference in ORRs between patients with GCN + and those with GCN- was even greater in <it>KRAS</it> wild-type patients, while in <it>KRAS</it> mutated patients the difference often did not exist. Almost all patients with <it>EGFR</it> amplification responded to the treatment. However, the prevalence of <it>EGFR</it> amplification was generally low. Incomplete data on progression-free survival and overall survival seemingly supported the findings on ORR.</p> <p>Conclusions</p> <p>Although increased <it>EGFR</it> GCN is generally associated with a better outcome of anti-EGFR MAbs treatment, especially among patients with wild-type <it>KRAS</it>, the clinical utility of this biomarker for selecting recipients of anti-EGFR MAbs would be severely limited by the heterogeneous scoring system and the poor reproducibility of <it>EGFR</it> GCN enumeration due to technical reasons.</p>