Meta-Analysis
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2015; 21(14): 4365-4372
Published online Apr 14, 2015. doi: 10.3748/wjg.v21.i14.4365
Anti-epidermal growth factor receptor monoclonal antibodies in metastatic colorectal cancer: A meta-analysis
Qi-Bin Song, Qi Wang, Wei-Guo Hu
Qi-Bin Song, Qi Wang, Wei-Guo Hu, Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
Author contributions: Song QB, Wang Q and Hu WG contributed equally to this work; Song QB designed the research; Wang Q performed the research; Hu WG analyzed the data; Wang Q wrote the paper.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Qi-Bin Song, Professor, Department of Oncology, Renmin Hospital of Wuhan University, Zhangzhidong District, Wuhan 430060, Hubei Province, China. qibinsong@163.com
Telephone: +86-27-88041911 Fax: +86-27-88041911
Received: July 20, 2014
Peer-review started: July 20, 2014
First decision: August 15, 2014
Revised: September 10, 2014
Accepted: October 15, 2014
Article in press: October 15, 2014
Published online: April 14, 2015
Abstract

AIM: To investigate the correlation between Kirsten rat sarcoma viral oncogene homolog (KRAS) status and the therapeutic effects of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs) in metastatic colorectal cancer (mCRC).

METHODS: Randomized controlled trials (RCTs) were identified and the association between KRAS mutation and clinical outcome in mCRC patients treated with anti-EGFR MoAbs was investigated. Ten RCTs were included in this meta-analysis. Progression-free survival and overall survival were used to assess the strength of the relationship between KRAS mutation and clinical outcome.

RESULTS: In first-line treatment, survival benefit was confined to patients with wild-type KRAS. Chemotherapy regimens and angiogenesis inhibitor treatment influenced the results of the analysis. Wild-type KRAS mCRC patients did not seem to benefit from oxaliplatin-based chemotherapy (PFS: HR = 0.88, 95%CI: 0.70-1.10; OS: HR = 0.93, 95%CI: 0.82-1.04). Clinical benefit in mCRC patients was limited to therapeutic regimens which included anti-EGFR MoAbs and fluorouracil-based therapy (PFS: HR = 0.77, 95%CI: 0.69-0.86; OS: HR = 0.85, 95%CI: 0.75-0.95). When anti-EGFR MoAbs were used as second- or further-line treatment, clinical benefit was still confined to patients with wild-type KRAS.

CONCLUSION: KRAS status is a potential predictive marker of clinical benefit due to anti-EGFR MoAb therapy in mCRC patients.

Keywords: Colorectal neoplasm, Kirsten rat sarcoma viral oncogene homolog, Cetuximab, Panitumumab, Meta-analysis

Core tip: In this study, we evaluated the correlation between Kirsten rat sarcoma viral oncogene homolog (KRAS) status and the therapeutic effects of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs) in patients with metastatic colorectal cancer. We focused on the relationship between KRAS status and the curative effect of anti-EGFR MoAbs in patients with metastatic colorectal cancer, and conducted a systematic meta-analysis of chemotherapy regimens, line of treatment and bevacizumab treatment. This analysis provides the first evidence that patients with wild-type KRAS metastatic colorectal cancer may not benefit from anti-EGFR MoAbs and oxaliplatin-based therapy as first-line treatment. Clinical benefit was confined to therapeutic regimens which included anti-EGFR MoAbs and fluorouracil-based therapy.