Edoxaban is an effective treatment option for patients with cancer associated venous thromboembolism

Cancer patients face an increased risk for venous thromboembolism (VTE). The current treatment guidelines for cancer-associated thrombosis (CAT) prescribe 3 to 6 months of low-molecular-weight heparin (LMWH). In recent years, several new direct oral anticoagulants (DOAC) were developed. These agents are now widely used for the treatment of VTE in patients without cancer, but their role in patients with CAT is uncertain. Results of the phase III HOKUSAI trial, presented at ASH 2017, demonstrate that the DOAC edoxaban is as effective as the LMWH dalteparin and could therefore offer an alternative treatment strategy for patients with CAT.

In the presented randomised, open-label non-inferiority trial, cancer patients with acute symptomatic or incidental VTE were assigned to receive LMWH for a minimum of 5 days followed by the oral factor Xa inhibitor edoxaban at a dose of 60 mg once daily (or 30 mg once daily in patients with a creatinine clearance of 30 to 50 ml per minute or a body weight below 60 kg), or subcutaneous dalteparin 200 units per kg once daily for one month followed by 150 units per kg thereafter. Patients received these regimens for up to 12 months. The primary outcome was the composite of the first recurrent VTE or major bleeding event during follow-up for 12 months. Secondary endpoints of the trial included recurrent VTE and major bleeding analysed separately, and survival, free of recurrent VTE or major bleeding.

The trial enrolled 1,050 individuals from 114 centres in 13 countries. Patients had a wide range of cancer types and were treated with different chemotherapy regimens. About 10% of patients had a haematological malignancy and the rest had solid tumours. At study entry, pulmonary embolism with or without deep-vein thrombosis was present in 657 patients (63%) while the remainder had isolated deep-vein thrombosis. Of the 1,050 patents, 706 (67%) had symptomatic VTE and the rest was incidental. Active cancer at entry was present in 97% of the patients and 53% had metastatic disease.

The study showed that edoxaban is non-inferior to dalteparin with respect to the composite endpoint of recurrent clots and bleeding, which occurred in 12.8% of patients receiving edoxaban and in 13.5% of patients treated with dalteparin (HR[95%CI]: 0.97[0.70-1.36]). Although edoxaban was associated with a slightly higher rate of major bleeding compared to dalteparin (6.3% vs. 3.2%), this was balanced by a slightly lower rate of recurrent VTE (6.5% vs. 10.3). The frequencies of severe major bleeding events (categories 3 and 4) were similar during treatment with edoxaban and dalteparin (12 patients, corresponding with 2.3% in both treatment arms). Also the event free survival, defined as survival free of death, major bleeding, or recurrent VTE, was similar for both treatments.

In summary, oral edoxaban for up to 12 months was non-inferior to subcutaneous dalteparin in the treatment of cancer-associated VTE. The lower rate of recurrent VTE observed with edoxaban was balanced by a similar increase in the risk of major bleeding. The rate of severe major bleeding and the event-free survival were similar for both treatments. As such, the investigators concluded that oral edoxaban could replace the injectable dalteparin in the vast majority of patients with CAT. It is important to note that these findings do not necessarily apply to all DOACs, given the fact that some act through different mechanisms, or are metabolized differently than edoxaban.

Reference

Raskob G, Van Es N, Verhamme P, et al. A Randomized, Open-Label, Blinded Outcome Assessment Trial Evaluating the Efficacy and Safety of LMWH/Edoxaban Versus Dalteparin for Venous Thromboembolism Associated with Cancer: Hokusai VTE-Cancer Study. Presented at ASH 2017; Abstract LBA-6.