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A systematic review and meta-analysis on the effect of angiogenesis blockade for the treatment of gastric cancer

Authors Bai ZG, Zhang ZT

Received 28 March 2018

Accepted for publication 1 June 2018

Published 17 October 2018 Volume 2018:11 Pages 7077—7087

DOI https://doi.org/10.2147/OTT.S169484

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 4

Editor who approved publication: Dr Carlos E Vigil


Zhi-Gang Bai, Zhong-Tao Zhang

Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Cancer Invasion and Metastasis Research and National Clinical Research Center for Digestive Diseases, Beijing 100050, People’s Republic of China

Introduction: To date, anti-vascular endothelial growth factor (VEGF) monoclonal antibody (mAb, bevacizumab), anti-VEGF receptor mAb (ramucirumab) and selective vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (sunitinib, sorafenib and apatinib) have been tested in the clinical trials.
Materials and methods: In the current study, results of 32 clinical trials (24 Phase I or II, 8 Phase III) were systematically reviewed and meta-analysis was performed in 8 Phase III trial results.
Results: It was found that median overall survival (OS) time and progression-free survival (PFS) time were significantly longer in the patients treated with antiangiogenic reagents compared to that in the patients with placebo when all of 8 Phase III clinical trials were analyzed together (OS: odds ratio = 0.805, 95% CI: 0.719–0.901, P < 0.001; PFS: odds ratio = 0.719, 95% CI: 0.533–969, P = 0.030).
Conclusion:
Meta-analysis on bevacizumab (4 out 8 Phase III trials) indicated that neither OS nor PFS was significantly different between the groups treated with bevacizumab or placebo with or without combination of other chemotherapeutic reagents (OS: odds ratio = 0.909, 95% CI: 0.780–1.059, P = 0.221; PFS: odds ratio = 0.985, 95% CI: 0.865–1.122, P = 0.826). By contrast, meta-analysis on ramucirumab (3 out of 8 Phase III trials) revealed that ramucirumab was significantly favored in the treatment of gastric cancer with significant different OS between the two groups (odds ratio = 0.720, 95% CI: 0.604–0.858, P < 0.001). In addition, patients treated with VEGF or VEGFR blockers had higher morbidity of hypertension and neutropenia, but lower risk of side effects of vomiting and anemia. These findings suggest that addition of antiangiogenesis reagents, especially anti-VEGFR-mAb, to the first- or second-line chemotherapy could prolong patient’s OS and PFS time in the advanced or metastatic gastric cancer.

Keywords: anti-VEGF monoclonal antibody, anti-VEGF receptor mAb, VEGFR tyrosine kinase inhibitors, Phase III trial, overall survival, progression-free survival, chemotherapy

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