Net Clinical Benefit of Edoxaban for 12 versus 3 Months in Cancer-associated Isolated Distal Deep Vein Thrombosis: ONCO DVT study

Abstract Background The ONCO DVT (Edoxaban for 12 Months Versus 3 Months in Patients With Cancer With Isolated Distal Deep Vein Thrombosis) study has revealed the superiority of a 12-month versus 3-month edoxaban treatment in terms of fewer thrombotic events for cancer-associated isolated distal deep vein thrombosis; however, concern for increased bleeding with longer anticoagulation remains. Methods In this post-hoc analysis of the ONCO DVT study, we compared 12-month and 3-month edoxaban treatments in terms of the net adverse clinical events (NACE) as a composite endpoint of the primary endpoint (symptomatic recurrent VTE and VTE-related death at 12 months) and major secondary endpoint (major bleeding at 12-months) of the ONCO DVT study. The net clinical benefit of a 12-month over 3-month treatment was defined as the sum of the differences in the incidence of thrombotic and bleeding events between the 3-month and 12-month treatments. The weight of bleeding events was set at 1.0, and we assessed the changes in the net clinical benefit with weights of bleeding events set at 0.5 and 2.0. Results With a weight of bleeding events of 1.0, NACE occurred in 30 of 296 patients (10.1%) in the 12-month edoxaban group and in 42 of 305 patients (13.8%) in the 3-month edoxaban group. The net clinical benefit was 3.6% (95% CI, -1.5% to 8.8%). There was a significant treatment-by-subgroup interaction between the thrombocytopenia or cancer metastasis subgroup factors and the effect of the 12-month relative to the 3-month treatment for NACE. As the weights of bleeding events changed from 0.5 to 2.0, the net clinical benefit in the 12-month edoxaban group as compared to the 3-month edoxaban group became attenuated from 4.8% (95% CI, 0.5% to 9.0%) to 0.7% (95% CI, -5.7% to 7.1%). Conclusions The net clinical benefit of the 12-month over 3-month edoxaban treatment was not significant; however, the 12-month treatment had a numerically lower incidence of NACE than the 3-month treatment. Clinical Trial Registration ClinicalTrials.gov, NCT03895502 . Clinical Perspective What is new? The net clinical benefit of the 12-month over 3-month edoxaban treatment was not significant in terms of the net clinical adverse events (NACE) combined with symptomatic recurrent venous thromboembolism (VTE), VTE-related death, or major bleeding with a weight of bleeding events of 1.0, however, the 12-month group had a numerically lower incidence of the NACE than the 3-month group. The net clinical benefit of the 12-month over 3-month edoxaban treatment became attenuated as the weights of the bleeding events increased. What are the clinical implications? The present study revealed that the 12-month edoxaban treatment compared with the 3-month edoxaban treatment was basically favorable in terms of NACE; however, the net clinical benefit of the 12-month edoxaban treatment became attenuated as the weights of the bleeding events increased. Further studies should be required to evaluate the case fatality rate of each event and its impact on cancer treatment.