Arterial thromboembolic events (ATEs) in a pooled analysis of 5 randomized, controlled trials (RCTs) of bevacizumab (BV) with chemotherapy

3019 Background: BV (Avastin™) is a monoclonal antibody to VEGF with demonstrated survival benefit when combined with CT in metastatic colorectal cancer (mCRC). Individual safety data from several RCT’s suggested that adding BV to CT may increase the risk of ATEs. We conducted a pooled analysis to evaluate this potential safety signal. Methods: Data from 1745 pts with metastatic carcinomas (breast, colorectal, and non-small-cell lung) pooled from 5 RCTs of BV with CT were analyzed to assess ATE risk and identify predisposing factors in the context of overall clinical effect. Clinical parameters, including age, gender, development of proteinuria on study, and history of hypertension, diabetes, atherosclerosis, venous TE (VTE), and use of aspirin or a statin, were assessed for relationship to ATE occurrence by univariate analysis and a Cox proportional hazards regression model. Results: Within this pooled population, the addition of BV to CT increased the risk of ATE compared to CT alone (3.8% vs 1.7%, p < 0.01 by Chi-square test). In addition to BV treatment, history of atherosclerosis and age ≥65 were identified as independent risk factors by multivariate analysis (hazard ratios of 1.9, 2.9, and 2.2 respectively). Conclusion: The addition of BV to CT is associated with an increased risk of ATE in pts with metastatic carcinoma, especially those ≥65 years old with a prior history of atherosclerosis. The risk/benefit of BV in mCRC by ATE-risk group will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech AstraZeneca, Genentech, GlaxoSmithKline, Pfizer Genentech AstraZeneca, Genentech, Novartis Bristol-Myers Squibb, Genentech