Risk of arterial (ATE) and venous thromboembolism (VTE) in a population-based cohort of bevacizumab-treated metastatic colorectal cancer (mCRC) patients.

Abstract

545 Background: Bevacizumab is associated with both arterial (ATE) and venous thromboembolic (VTE) events, estimated to be </=15% from clinical trials. Our objectives were to 1) characterize the incidence of ATE or VTE among mCRC patients receiving bevacizumab in a non-clinical trial setting; 2) determine patient and treatment-related factors that predispose to an increased risk of ATE or VTE; and 3) explore how thromboembolism is managed and whether bevacizumab is discontinued and/or resumed after an event. Methods: A random sample of mCRC patients diagnosed between 2008 and 2009, referred to 1 of 5 regional cancer centers in British Columbia, and who were offered bevacizumab was reviewed. Summary statistics were used to describe and compare clinical factors between those who experienced an ATE or VTE and those who did not. Results: Of the 200 mCRC patients offered bevacizumab, 10 never received the drug and 12 were lost to follow up. Among the 178 remaining patients, median age was 61 years, 103 (58%) were male, and 121 (85%) had ECOG 0 to 1. A total of 39 patients (28%) experienced at least 1 documented thromboembolic event. Compared to patients who developed a clot, those who did not had similar median age (62 vs 61), gender distribution (23% men and 20% women), ECOG 0 to 1 (84% vs 85%) and body mass index (26.4 vs 25.3). However, the mean number of bevacizumab doses was higher in the group with thromboembolism (12.6 vs 9.0), suggesting a potential dose-related effect. There were a total of 43 VTE and 5 ATE events documented, with 7 of the 39 patients (18%) experiencing more than 1 event. Bevacizumab was held or discontinued in 60% of cases, but it was continued in 25% of the cases; 4% of the events were fatal, and 10% of the VTE/ATE occurred after bevacizumab was stopped. Conclusions: The incidence of ATE and VTE in a non-study setting appears to be higher than that reported in clinical trials. There may be a dose-related effect. Bevacizumab was not consistently held or discontinued in the setting of a VTE or ATE. Development of guidelines for the management of thromboembolism with bevacizumab may be warranted.