Risk of venous and arterial thromboembolic events in patients with metastatic breast cancer treated with bevacizumab: A meta-analysis.

Abstract

1043 Background: The use of bevacizumab, a vascular endothelial growth factor inhibitor, has been associated with an increase in risk of arterial thromboembolic events (ATE) and venous thromboembolic events (VTE) in some clinical trials. The aim of this systematic review and meta-analysis of randomized trials was to assess the overall risk of both grade 3-5 ATE and VTE associated with bevacizumab in patients with metastatic breast cancer (MBC). Methods: We selected all randomized phase III trials which compared chemotherapy with or without bevacizumab in MBC. For the analysis, we used a fixed-effects and random effects models to calculate the pooled event-based relative risk ratios (RR) with 95% confidence interval (CI). The Cochran's Q statistic and I2 statistics were first calculated to assess the heterogeneity among the proportions of the included trials. For this study, we collected all grade 3-5 events reported in these trials. We analyzed the overall RR for vascular events (ATE + VTE) because differentiation between ATE and VTE was not clearly defined in some studies. Results: Five trials were included in the meta-analysis: E2100, AVADO, RIBBON-1, RIBBON-2 and AVF-2119g. In total, 2,368 patients received bevacizumab-based therapy and 1,416 chemotherapy alone. Vascular events were reported in 72 and 41 patients, respectively. There was a tendency for heterogeneity (p=0.082) considering all trials, so both the fixed-effects and the random-effects models were used. Patients treated with bevacizumab-containing regimens had a RR for vascular events of 1.095 (95% CI, 0.747-1.606; p=COPY fixed-model) and 1.066 (95% CI, 0.596-1.908; p=0.829) (random-model). Conclusions: Although patients with MBC treated with chemotherapy present a remarkable risk of vascular events, the addition of bevacizumab to chemotherapy did not increase the risk of VTE and ATE in this patient population. No significant financial relationships to disclose.