Venous thromboembolic events with chemotherapy plus bevacizumab: a pooled analysis of patients in randomized phase II and III studies.
PURPOSE: Thromboembolism is a major source of morbidity and mortality in patients with cancer. The contribution of anti-vascular endothelial growth factor therapy to these events remains controversial. PATIENTS AND METHODS: Individual patient data were available for 6,055 patients in 10 randomized studies. Unadjusted and exposure-adjusted incidence of venous thromboembolisms (VTEs) was estimated for the overall population and by tumor type. Multivariate analysis was performed to identify risk factors for development of VTE. The safety of anticoagulant therapy in patients undergoing bevacizumab treatment was also examined. RESULTS: There were no statistically significant increases in the unadjusted or exposure-adjusted incidences of all-grade VTEs for bevacizumab versus controls in the overall population or by tumor type. The unadjusted incidence in the overall population was 10.9% with bevacizumab versus 9.8% with controls (odds ratio, 1.14; 95% CI, 0.96 to 1.35; P = .13); the rate per 100 patient-years was 18.5 for bevacizumab and 20.3 for controls (rate ratio, 0.91; 95% CI, 0.77 to 1.06; P =.23). Incidences of grade 3 to 5 events were similar in both groups. Several risk factors for VTEs were identified, including tumor type, older age, poorer performance status, VTE history, and baseline oral anticoagulant use. No interactions between bevacizumab treatment and these factors were observed. For patients who had a VTE and received full-dose anticoagulation therapy, the risk of severe bleeding was low (< 1%) and unaffected by bevacizumab treatment. CONCLUSION: The addition of bevacizumab to chemotherapy did not statistically significantly increase the risk of VTEs versus chemotherapy alone. The risk for VTEs is driven predominantly by tumor and host factors.
Hurwitz, HI; Saltz, LB; Van Cutsem, E; Cassidy, J; Wiedemann, J; Sirzén, F; Lyman, GH; Rohr, U-P
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