Factor XI inhibitors in cancer-associated venous thromboembolism: what’s next?

Venous thromboembolism (VTE) is an important cause of morbidity and mortality in individuals with active cancer. Most cancer-associated VTE occurs in the ambulatory setting in individuals receiving systemic therapy. Multiple anticoagulants are currently available for the treatment of cancer-associated VTE; a major drawback is the risk of bleeding. No drugs are currently approved for primary prevention of VTE in cancer in the outpatient setting. Adherence/compliance issues, drug-drug interactions, and concern about renal and hepatic metabolism are other ongoing concerns with these agents. Thus, there are major unmet needs in the quest to optimize the treatment and prevention of VTE in cancer. Factor XI (FXI) has only a small impact on hemostasis but contributes significantly to thrombosis. It is therefore a potential therapeutic target with less concern for enhancing bleeding. Several early-phase studies suggest that FXI inhibitors have reduced the risk of bleeding at therapeutic doses in the prevention of venous and arterial events in cardiology and postoperative settings. Multiple studies are now addressing the utility of this new class of drugs in cancer-associated VTE, including completed, ongoing, and planned trials of primary prevention and treatment. This narrative review addresses the role of FXI in thrombosis, the rationale for FXI inhibitors in primary and secondary prevention settings in malignancy and provides an overview of preliminary results and future directions.