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VTE in patients with cancer – treatment guidance – evidence from RCTs
Learn about the use of NOACs in the treatment of CAT
Venous thromboembolism (VTE) is a leading cause of mortality and morbidity in patients with cancer.1 The risk of VTE is ~4–7-times higher in patients with cancer compared with those without, and the risk varies by cancer type.1 Approximately 20% of all VTE cases are attributable to cancer;2 such cases are otherwise known as cancer-associated thrombosis (CAT).
Risk of VTE in patients with cancer compared with those without1
Anticoagulant therapy is the mainstay of VTE treatment,3 but can be challenging in patients with cancer because they have a higher risk of VTE recurrence and bleeding than patients without cancer.4,5 In addition, some side effects of cancer treatments, such as thrombocytopenia and gastric disturbances, and the need for frequent interventions, further complicate the use of anticoagulants in these patients.6,7
For the treatment of acute VTE in patients with cancer, guidelines recommend the use of low molecular weight heparins (LMWHs) over vitamin K antagonists (VKAs) based on the better efficacy of LMWHs over VKAs, as demonstrated in several randomized controlled trials (RCTs) in patients with CAT.3,8-11
Despite the evolution from VKAs to LMWHs as the standard of care, anticoagulation treatment for CAT still has limitations. The residual risk of recurrent VTE remains high for patients receiving LMWHs, with a reported incidence of approximately 7–9%.8,12 In addition, treatment with LMWHs has been associated with various challenges, including the burden of daily injections and high treatment costs,3,13 which are especially important in patients who require long-term treatment. These factors are likely to contribute to the low persistence with long-term LMWH therapy observed in real-world evidence studies.14,15
Non-vitamin K antagonist oral anticoagulants (NOACs), such as rivaroxaban, edoxaban, dabigatran and apixaban, may be able to overcome some of the challenges associated with VKAs and LMWHs.7
The phase III Hokusai-VTE-Cancer study and the select-d pilot study provide the first randomized comparisons of NOACs versus LMWH in patients with CAT.16,17
In the Hokusai-VTE-Cancer study, treatment with edoxaban (60 mg once daily [od]) for up to 12 months was found to be non-inferior to dalteparin for the composite primary outcome of recurrent VTE or major bleeding in patients with CAT.16 Although the rate of recurrent VTE was reduced, the rate of major bleeding was significantly increased with edoxaban versus dalteparin.16 The results of the select-d study demonstrated that rivaroxaban (15 mg twice daily [bid] for 3 weeks followed by 20 mg od) was associated with a lower cumulative rate of VTE recurrence at 6 months than dalteparin in patients with CAT.17 However, the cumulative rate of major and clinically relevant non-major bleeding at 6 months was increased with rivaroxaban versus dalteparin.17 The majority of bleeding events in these studies occurred in the upper gastrointestinal tract of patients with gastrointestinal cancer.16,17
Based on these data, NOACs may be an effective alternative to LMWH for the treatment of VTE in patients with cancer.16,17 However, the increased bleeding risk, particularly in certain subsets of patients with cancer, suggests that patients who might benefit from this regimen need to be selected carefully.16,17
Patients with cancer are at an increased risk of experiencing VTE compared with those without cancer. Current guidelines recommend the use of LMWH over VKAs for the treatment of CAT. However, daily injections and the costs of LMWH therapy hinder long-term use, which is needed for the prevention of recurrent thrombotic events. NOACs circumvent some of the challenges associated with VKAs and LMWHs. Evidence from recent RCTs suggest that NOACs, such as edoxaban and rivaroxaban, are an effective alternative to LMWHs in the prevention of recurrent VTE in patients with CAT.
Real-world evidence has shown that NOACs are being widely used in patients with cancer in clinical practice, starting from before this was supported by evidence from RCTs.5 There are several studies reporting the use of rivaroxaban for the treatment of CAT in clinical practice,18-20 but real-world data for apixaban, dabigatran and edoxaban are lacking. Studies, such as the US prospective cohort study conducted by the Memorial Sloan Kettering Cancer Center or the subgroup analysis of the non-interventional XALIA study, provide some reassurance for the use of rivaroxaban in the treatment of CAT in a clinical setting.18,19