Meta-Analysis
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 14, 2015; 21(22): 7022-7035
Published online Jun 14, 2015. doi: 10.3748/wjg.v21.i22.7022
Standard chemotherapy with cetuximab for treatment of colorectal cancer
Xin-Xiang Li, Lei Liang, Li-Yong Huang, San-Jun Cai
Xin-Xiang Li, Lei Liang, Li-Yong Huang, San-Jun Cai, Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
Xin-Xiang Li, Lei Liang, Li-Yong Huang, San-Jun Cai, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Author contributions: Li XX participated in data collection and analysis, and wrote the manuscript; Liang L and Huang LY participated in data collection and help to perform the statistical analysis; Cai SJ conceived of the study, participated in its design and provided the critical revision; all authors read and approved the final manuscript.
Conflict-of-interest: All the authors declare no conflicts of interest.
Data sharing: Technical appendix, statistical code, and dataset available from the corresponding author at cai_sanjunsci@163.com.
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: San-Jun Cai, MD, Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai 200032, China. cai_sanjunsci@163.com
Telephone: +86-21-64085875 Fax: +86-21-64085875
Received: October 17, 2014
Peer-review started: October 19, 2014
First decision: December 2, 2014
Revised: December 12, 2014
Accepted: February 12, 2015
Article in press: February 13, 2015
Published online: June 14, 2015
Abstract

AIM: To review and assess the evidence related to cetuximab treatment in metastatic colorectal cancer (mCRC) with regard to KRAS status.

METHODS: PubMed, EMBASE, Cochrane database and American Society of Clinical Oncology meeting abstracts were searched for randomized controlled trials (RCTs) reporting the effect of KRAS status on efficacy of chemotherapy regimen with or without cetuximab in mCRC. Baseline information such as sex and age was summarized from the included studies. Hazard ratios of progression-free survival (PFS) and overall survival (OS) as well as objective response based on KRAS status were extracted for analysis.

RESULTS: A total of 8 RCTs with 6780 patients were included. The combined analysis showed that cetuximab failed to improve the OS and PFS in patients with mCRC. However, in subgroup analysis, the pooled data showed that addition of cetuximab to irinotecan containing chemotherapy regimen was sufficient to improve OS and PFS in wild-type KRAS mCRC patients, but not in patients with mutant-type KRAS. The addition of cetuximab increased the incidence of adverse events such as diarrhea, rash, skin toxicity/rash, and nausea and vomiting. There was no significant publication bias existing in the included studies.

CONCLUSION: The clinical benefit of cetuximab was only confirmed in patients with wild-type KRAS. KRAS status could be considered a biomarker of efficacy of cetuximab.

Keywords: Cetuximab, KRAS, Standard chemotherapy, Metastatic colorectal cancer, Meta-analysis

Core tip: The addition of cetuximab to irinotecan containing chemotherapy regimen was sufficient to improve overall survival and progression-free survival in wild-type KRAS metastatic colorectal cancer patients, but not in patients with mutant-type KRAS.