Back to Journals » OncoTargets and Therapy » Volume 11

Efficacy of bevacizumab versus epidermal growth factor receptor inhibitors for wild-type RAS metastatic colorectal cancer: a meta-analysis

Authors Jiang W, Yu Q, Ning R, Zhao W, Wei C

Received 20 March 2018

Accepted for publication 24 May 2018

Published 24 July 2018 Volume 2018:11 Pages 4271—4281


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Sanjeev Srivastava

Wei Jiang,1,* Qitao Yu,1,* Ruiling Ning,1 Wenhua Zhao,1 Changyuan Wei2

1Department of Medical Oncology, Tumor Hospital Affiliated to Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Breast Surgery, Tumor Hospital Affiliated to Guangxi Medical University, Nanning, People’s Republic of China

*These authors contributed equally to this work

Background: Results from several prospective clinical trials comparing anti-epidermal growth factor receptor (EGFR) therapy and anti-vascular endothelial growth factor (VEGF) therapy plus chemotherapy for wild-type RAS metastatic colorectal cancer (mCRC) have been inconsistent. This meta-analysis aims to investigate the optimal choice for these target agents.
Methods: We searched for clinical trials in both electronic databases from inception until January 2018 and recent conference abstracts to identify prospective clinical studies comparing the efficacy of a VEGF inhibitor (bevacizumab) versus EGFR inhibitors (cetuximab or panitumumab) on wild-type RAS (including its subset KRAS) mCRC. All analyses were conducted using RevMan 5.3 software.
Results: A total of 5 studies were included. EGFR inhibitors were associated with a significant benefit in terms of overall survival (OS) compared with VEGF inhibitors in wild-type KRAS or wild-type RAS populations, with hazard ratios (HRs) equal to 0.86 (95% CI: 0.78, 0.95; p=0.003) and 0.83 (95% CI: 0.72, 0.95; p=0.007), respectively. This survival benefit was limited to the first-line setting. No difference was found for progression-free survival (PFS), whereas the objective response rate (ORR) was significantly increased in the wild-type RAS population (OR: 0.64; 95% CI: 0.50, 0.82; p=0.0004). No difference in OS was noted between EGFR inhibitors versus a VEGF inhibitor plus the FOLFIRI regimen, whereas superior survival was noted for EGFR inhibitors plus the mFOLFOX6 regimen versus a VEGF inhibitor (HR: 0.75; 95% CI: 0.57, 0.98; p=0.04). PFS was significantly prolonged (HR: 1.48; 95% CI: 1.14, 1.92; p=0.003), whereas a trend favoring OS (HR: 1.23; 95% CI: 0.93, 1.63; p=0.14) was noted for a VEGF inhibitor in patients with right-sided tumors, with no difference in the ORR (OR: 0.85; 95% CI: 0.52, 1.38; p=0.51). However, left-sided tumors exhibited superior OS (HR: 0.71; 95% CI: 0.59, 0.85; p=0.0002), PFS (HR: 0.84; 95% CI: 0.72, 0.98; p=0.03), and ORR (OR: 0.66; 95% CI: 0.48, 0.92; p=0.01) for EGFR inhibitors.
Conclusion: This meta-analysis suggests the superiority of anti-EGFR therapy compared with anti-VEGF therapy for mCRC with wild-type RAS. Primary tumor location should be taken into account in target drug selection. Further research is still needed to confirm which inhibitor may be a better choice when combined with different chemotherapy regimens.

Keywords: bevacizumab, cetuximab, panitumumab, colorectal cancer, meta-analysis

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]