To the Editor: The meta-analysis assessing the risk of venous thromboembolism (VTE) with bevacizumab in cancer patients by Dr Nalluri and colleagues1 carefully reviewed 15 well-conducted randomized controlled trials (RCTs) comparing bevacizumab therapy with placebo. However, because the authors failed to distinguish between incidence per treatment episode and incidence per unit of time (the more relevant statistic), their conclusions may be erroneous. In oncology clinical trials such as those reviewed, patients are generally not treated for a predetermined fixed period of time; rather, they are treated until their cancer shows evidence of progression on computed tomographic scans, at which time the patient is removed from the trial and further adverse events are not recorded beyond 30 days after the end of treatment.
Because bevacizumab is a beneficial oncology drug, the patients in these trials often stayed on treatment with bevacizumab much longer than placebo, giving them more time to develop adverse events such as venous thromboembolism. For example, in the study by Hurwitz et al,2 the median progression-free survival with bevacizumab was 10.6 months vs 6.2 months with placebo. Because time on treatment is very close to time to progression, this is a 70% increase in time available for an adverse event to occur. For Miller et al,3 the increase was 100%, and for Sandler et al,4 37%. Nalluri et al relied on the published data that give crude incidence of thromboembolism per treatment episode, not incidence per unit of time. Given the considerably longer period on treatment for patients receiving bevacizumab, it is no surprise that 33% more venous thromboemboli were recorded in the groups receiving bevacizumab. At the minimum, the data should have been corrected for the published figures for median progression-free survival.
Financial Disclosures: Dr Minor reported receiving research funds from Genentech as an investigator in a multicenter trial.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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