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

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.