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

Journal of Hematology & Oncology

Jin-Ling Tang¹  Chen Mao¹  Jin-Zhang Chen²  Ya-Fang Huang¹  Xin-Yin Wu¹  Da-Yong Zheng²  Xue-Feng Hu¹  Wei-Xi Shen³  Zu-Yao Yang¹ 

[1] Division of Epidemiology, the Jockey Club School of Public Health and Primary Care, the Chinese University of Hong Kong, Hong Kong, People’s Republic of China;Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China;Cancer Institute, the Second Clinical Medical College, Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong Province, People’s Republic of China

关键词: Meta-analysis;    Systematic review;    Epidermal growth factor receptor;    Panitumumab;    Cetuximab;    Monoclonal antibodies;    Colorectal neoplasms;   

Others  :  822195
DOI  :  10.1186/1756-8722-5-52

 received in 2012-06-21, accepted in 2012-07-17,  发布年份 2012

【 摘 要 】

Background

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.

Methods

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2012 Yang et al.; licensee BioMed Central Ltd.

【 图 表 】

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