Comparison of an oral factor Xa inhibitor with low molecular weight heparin in cancer patients with venous thromboembolism : results of a randomized trial (SELECT-D)

Purpose: Venous thromboembolism (VTE) is common in cancer patients. Long-term daily subcutaneous low molecular weight heparin has been standard treatment for such patients. The purpose of this study was to assess if an oral Factor Xa inhibitor, rivaroxaban, would offer an alternative treatment for VTE in cancer patients. Patient and Methods: In this UK multicentre, randomised, open-label, pilot trial, patients with active cancer who had symptomatic pulmonary embolism (PE), incidental PE or symptomatic lower extremity proximal deep vein thrombosis (DVT) were recruited. Allocation was to dalteparin (200 IU/kg daily, month 1, then 150 IU/kg, months 2-6) or rivaroxaban (15 mg twice daily for three weeks, then 20 mg once daily) for six months. The primary outcome was VTE recurrence over six months. Safety was assessed by major bleeding and clinically relevant non-major bleeding (CRNMB). A sample size of 400 patients would provide estimates of VTE recurrence to within +/ 4.5% assuming a VTE recurrence rate at six months of 10%. Results: Two hundred and three patients were randomised to each group; 58% of whom had metastases. Twenty-six patients experienced recurrent VTE (18 dalteparin, 8 rivaroxaban). The six month cumulative VTE recurrence rate with dalteparin was 11% (95% CI 7-16%) and 4% (95% CI 2-9%) with rivaroxaban, hazard ratio (HR) 0.43, (95% CI 0.19-0.99). The six month cumulative rate of major bleeding was 4% (95% CI 2-8%) for dalteparin and 6% (95% CI 3-11%) for rivaroxaban, HR 1.83, (95% CI 0.68-4.96). Corresponding rates of CRNMB were 4% (95% CI 2-9%) and 13% (95% CI 9-19%) respectively, HR 3.76, (95% CI 1.63-8.69). Conclusion: Rivaroxaban was associated with relatively low VTE recurrence but higher CRNMB compared to dalteparin