Do Antiangiogenics Promote Clot Instability? Data from the TESEO Prospective Registry and Caravaggio Clinical Trial

Abstract

Background: Venous thromboembolism (VTE) is a common complication in cancer patients. Much of its morbidity stems from the development of fatal pulmonary embolisms (PE). Little is known about the factors involved in clot stability, with angiogenesis possibly being implicated. Methods: The database is from the TESEO prospective registry that recruits cancer patients with VTE from 41 Spanish hospitals. Independent validation was conducted in a cohort from the Caravaggio trial. The objective is to evaluate the association between exposure to antiangiogenic therapies and the PE/VTE proportion in oncological patients. Results: 1536 subjects were evaluated; 58.4% (n=894) had a PE and 7% (n=108) received antiangiogenic therapy (bevacizumab in 75%). The PE/VTE proportion among antiangiogenic-treated individuals was 77/108 (71.3%) versus 817/1428 (57.2%) among those receiving other alternative therapies (p=0.004). The effect of the antiangiogenics on the PE/VTE proportion held up across all subgroups except for active smokers or those with chronic obstructive pulmonary disease. Exposure to antiangiogenics was associated with increased PEs, odds ratio (OR) 2.27 (95% CI, 1.42-3.63). In the Caravaggio trial, PE was present in 67% of the individuals treated with antiangiogenics, 50% of those who received chemotherapy without antiangiogenic treatment, and 60% without active therapy (p=0.0016). Conclusions: Antiangiogenics are associated with increased proportion of PE in oncological patients with VTE. If an effect on clot stability is confirmed, the concept of thrombotic risk in cancer patients should be reconsidered in qualitative terms.

Angiogenesis in Chronic Thromboembolic Pulmonary Hypertension: A Janus-Faced Player?

“…The reported incidence of venous thromboembolism encountered in patients under antiangiogenic therapy ranges from 1% to 14% per year, highlighting the complex interplay between angiogenesis and the clotting system. 64,66 Recently, the use of antiangiogenic drugs in oncological patients has been shown to be associated with increased proportion of PE, 67 suggesting that such molecules could contribute to clot instability. Adverse events related to venous thromboembolism have also been reported in patients with age-related macular degeneration treated with intravitreal anti-VEGF agents.…”