Antineoplastic therapies associated with venous thromboembolism: disproportionality analysis of the WHO database

The risk of venous thromboembolic events (VTE) is elevated in patients with active cancer. Recent antineoplastic therapies, including immunotherapies and targeted therapies, may further increase VTE risk, although evidence is limited. In March 2024, we conducted a disproportionality analysis using reporting odds ratios (Reporting-OR) in VigiBase, the World Health Organization's (WHO's) pharmacovigilance database, to assess the association between 280 antineoplastic therapies approved by the US Food and Drug Administration and/or the European Medicines Agency and VTE (symptomatic or not), defined as deep vein thrombosis and/or pulmonary embolism. Reporting-OR were adjusted (aReporting-OR) for case characteristics, including primary tumor site and metastatic status. A total of 37 803 VTE reports associated with at least 1 antineoplastic therapy were identified. We identified 19 antineoplastic therapies significantly associated with an increased reporting of VTE, with nintedanib emerging as a newly recognized association. The strongest associations were observed for lenalidomide (aReporting-OR, 3.64; 95% confidence interval [CI], 3.47-3.82), bevacizumab (aReporting-OR, 3.64; 95% CI, 3.43-3.86), and cyproterone (aReporting-OR, 3.52; 95% CI, 2.55-4.87). The median time to VTE onset was 64 days (interquartile range, 27-143), with 81% of VTE events occurring within the first 6 months after antineoplastic therapy initiation. Future studies should include antineoplastic therapies in VTE risk assessments and evaluate the management of VTE when recurrences occur while under treatment. This trial was registered at www.clinicaltrials.gov as NCT04696250.