Risk of Venous Thromboembolism With Bevacizumab in Cancer Patients—Reply

In Reply: We recognize that potential biases may exist because of possible differences in follow-up times or related chemotherapies between bevacizumab and control groups, as pointed out by Dr Minor and by Dr Cortes and colleagues. The prolonged time to progression frequently associated with bevacizumab therapy might result in more follow-up time or exposure to chemotherapy in bevacizumab groups, potentially leading to increased VTE. However, we analyzed 3 RCTs in which bevacizumab was not associated with significant progression-free survival^1- 3 and 1 trial in which follow-up time was not significantly different between the bevacizumab group (median, 13.3 months; range, 0-25.6 months) and controls (median, 12.8 months; range, 0-24.2 months).⁴ We found that the RR of VTE with bevacizumab from these 4 RCTs was 1.39 (95% confidence interval [CI], 0.97-2.01). In addition, the RR was 1.32 (95% CI, 1.10-1.59) from 10 RCTs in which the follow-up time was not specified for bevacizumab group and control, and bevacizumab was associated with significantly prolonged time to progression. Thus, it appears that the potential bias may be limited.