Efficacy and safety of bevacizumab-based combination therapy for treatment of patients with metastatic colorectal cancer
Authors Xu R, Xu C, Liu C, Cui C, Zhu J
Received 20 April 2018
Accepted for publication 3 September 2018
Published 4 December 2018 Volume 2018:11 Pages 8605—8621
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Yao Dai
Ran Xu,1,2,* Chen Xu,1,* Chuntong Liu,3 Can Cui,4 Jing Zhu5
1Medical School of Nantong University, Jiangsu 226001, China; 2Huai’an Key Laboratory of Gastrointestinal Cancer, Jiangsu 223001, China; 3XuZhou Medical University, Jiangsu 221000, China; 4Macau University of Science and Technology, Macau 519020, China; 5Department of Oncology, The Affiliated Huaian NO 1 People’s Hospital of Nanjing Medical University, Jiangsu 223001, China
*These authors contributed equally to this work
Aim: The use of bevacizumab in combination therapy is an emerging trend in metastatic colorectal cancer treatment. However, the clinical value of different combination types remains under debate. Thus, a meta-analysis of randomized controlled trials (RCTs) comparing bevacizumab-based combination therapy with monotherapy (therapy that uses one type of treatment, such as chemotherapy or surgery alone, to treat metastatic colorectal cancer) was performed, aiming to evaluate the safety and efficacy of bevacizumab-based combination therapy and to find a more beneficial combination.
Methods: We searched for clinical studies that evaluated bevacizumab-based combination therapy in metastatic colorectal cancer. We extracted data from these studies to evaluate the relative risk (RR) of overall response rate (ORR) and grade 3/4 treatment-related adverse events (AEs), HRs of overall survival (OS), and progression-free survival (PFS).
Results: Eight RCTs were identified (n=3,424). Treatments included combinations of bevacizumab and oxaliplatin, fluorouracil, and leucovorin (FOLFOX4), combinations of bevacizumab and capecitabine and oxaliplatin, combinations of bevacizumab and fluorouracil/leucovorin, combinations of bevacizumab and irinotecan, fluorouracil, and leucovorin (IFL), and combinations of bevacizumab and capecitabine. Bevacizumab-based combination therapy showed higher ORR (RR: 1.40; 95% CI: 1.10–1.78; P=0.005), PFS (HR: 0.64; 95% CI: 0.55–0.73; P=0.000), and OS (HR: 0.82; 95% CI: 0.73–0.92; P=0.001) values than monotherapy. However, higher grade 3/4 treatment-related AEs (RR: 1.27; 95% CI: 1.15–1.41; P=0.000) were observed in combination therapy than in monotherapy.
Conclusion: This meta-analysis showed that the addition of IFL to bevacizumab better benefits PFS and safety. Adding FOLFOX4 was associated with better ORR and OS. The efficacy and safety of an IFL–bevacizumab–FOLFOX4 combination should be given greater weight in future clinical trials, guidelines, and clinical practice.
Keywords: combination therapy, bevacizumab, metastatic colorectal cancer, meta-analysis
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php 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]