Division of Epidemiology, the Chinese University of Hong Kong, Hong Kong, People's Republic of China.
J Hematol Oncol. 2012 Aug 16;5:52. doi: 10.1186/1756-8722-5-52.
Epidermal growth factor receptor gene copy number (EGFR 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.
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 EGFR 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 Q-test and the I2 statistic. If appropriate, a quantitative synthesis of data from different studies would be conducted with a random-effects model.
Nineteen eligible studies were identified. The criteria for increased EGFR 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 EGFR 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 KRAS wild-type patients, while in KRAS mutated patients the difference often did not exist. Almost all patients with EGFR amplification responded to the treatment. However, the prevalence of EGFR amplification was generally low. Incomplete data on progression-free survival and overall survival seemingly supported the findings on ORR.
Although increased EGFR GCN is generally associated with a better outcome of anti-EGFR MAbs treatment, especially among patients with wild-type KRAS, 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 EGFR GCN enumeration due to technical reasons.
表皮生长因子受体基因拷贝数（EGFR GCN）已被广泛研究，作为治疗转移性结直肠癌（mCRC）的潜在预测生物标志物，使用抗 EGFR 单克隆抗体（MAbs）。本研究的目的是系统回顾这方面的现有证据。
全面检索 PubMed、EMBASE、The Cochrane Library、中国生物医学文献数据库、万方数据和美国临床肿瘤学会和欧洲肿瘤内科学会会议摘要。纳入报告了接受抗 EGFR MAb 治疗的 mCRC 患者的客观缓解率（ORR）、无进展生存期和/或总生存期，按 EGFR GCN 状态分层的研究。二项结局（反应）和时间至事件结局（无进展生存期和总生存期）的效应测量指标分别为风险差和风险比。通过 Cochran's Q 检验和 I2 统计量评估研究间的统计异质性。如果适当，将采用随机效应模型对来自不同研究的数据进行定量综合。
确定了 19 项符合条件的研究。不同研究中增加 EGFR GCN（GCN+）的标准高度不一致。GCN+的发生率从 6.9%到 88.9%不等，GCN+患者与非增加 EGFR GCN（GCN-）患者的 ORR 差异从-28%到 84%不等。由于存在显著的异质性，因此未对数据进行定量综合。GCN+患者的 ORR 普遍较高，具有一般趋势。在 KRAS 野生型患者中，GCN+患者与 GCN-患者的 ORR 差异更大，而在 KRAS 突变型患者中，这种差异通常不存在。几乎所有 EGFR 扩增的患者均对治疗有反应。然而，EGFR 扩增的发生率普遍较低。无进展生存期和总生存期的不完全数据似乎支持 ORR 的发现。
尽管增加的 EGFR GCN 通常与抗 EGFR MAb 治疗的更好结果相关，尤其是在 KRAS 野生型患者中，但由于技术原因，由于评分系统的异质性和 EGFR GCN 计数的重现性差，该生物标志物用于选择抗 EGFR MAb 受体的临床实用性将受到严重限制。
