Edoxaban for 12 Months Versus 3 Months in Patients With Cancer With Isolated Distal Deep Vein Thrombosis (ONCO DVT Study): An Open-Label, Multicenter, Randomized Clinical Trial

Abstract

Background: The optimal duration of anticoagulation therapy for isolated distal deep vein thrombosis (DVT) in patients with cancer is clinically relevant, but the evidence is lacking. The prolonged anticoagulation therapy could have a potential benefit for prevention of thrombotic events, however, it could also increase the risk of bleeding. Methods: In a multicenter, open-label, adjudicator-blinded, randomized clinical trial at 60 institutions in Japan, we randomly assigned cancer patients with isolated distal DVT, in a 1-to-1 ratio, to receive either a 12-month or 3-month edoxaban treatment. The primary endpoint was a composite of a symptomatic recurrent venous thromboembolism (VTE) or VTE-related death at 12 months. The major secondary endpoint was major bleeding at 12 months, according to the criteria of the International Society on Thrombosis and Hemostasis. The primary hypothesis was that a 12-month edoxaban treatment was superior to a 3-month edoxaban treatment with respect to the primary endpoint. Results: From April 2019 through June 2022, 604 patients were randomized, and after excluding 3 patients who withdrew consent, 601 patients were included in the intention-to-treat population: 296 patients in the 12-month edoxaban group and 305 patients in the 3-month edoxaban group. The mean age was 70.8 years, 28% of the patients were men, and 20% of the patients had symptoms of DVT at baseline. The primary endpoint of a symptomatic recurrent VTE event or VTE-related death occurred in 3 of the 296 patients (1.0%) in the 12-month edoxaban group and in 22 of the 305 (7.2%) in the 3-month edoxaban group (odds ratio, 0.13; 95% CI, 0.03 to 0.44). The major secondary endpoint of major bleeding occurred in 28 of the 296 patients (9.5%) in the 12-month edoxaban group and in 22 of the 305 (7.2%) in the 3-month edoxaban group (odds ratio, 1.34; 95% CI, 0.75 to 2.41). The prespecified subgroups did not affect the estimates on the primary endpoint. Conclusions: In cancer patients with isolated distal DVT, 12 months was superior to 3 months for an edoxaban treatment with respect to the composite outcome of a symptomatic recurrent VTE or VTE-related death.

Clinical Course of Isolated Distal Venous Thromboembolism in Patients With Active Cancer in a Nation With an Overall Low Risk of Thrombosis

“…It should be noted that there was no VTE-related death at 12 months in either group of patients. 4 However, the risk of symptomatic recurrent VTE of 7.2% at 12 months in patients who stopped OAC at 3 months is higher than previously reported in the literature, showing a 4.8% (95% CI, 3.9 to 5.9) VTE recurrence rate at 12 months for isolated distal VTE in real-world practice. 7 Both arms in the current study had a higher incidence of recurrent VTE than seen in patients without cancer with extended treatment.…”

“…Death attributable to cancer was the most common event, regardless of the length of OAC treatment (21% and 20% in 3-month and 12-month OAC groups, respectively; Figure ). The results shown by Yamashita et al 4 affirm previously published data in patients with active cancer: a high risk of death at 1 year (cancer, 48.1% [95% CI, 43.4-53.2] versus no cancer, 3.2% [95% CI, 2.9-3.6]) and moderate risk of major bleeding (cancer, 9.7% [95% CI, 7.7-12.2] versus no cancer, 2.0% [95% CI, 1.7-2.3]) or VTE recurrence (cancer, 9.3% [95% CI, 7.4-11.8] versus no cancer, 4.6% [95% CI, 4.2-5.1]). 11 Because the mortality incidence was high in asymptomatic patients, the presence of VTE may be an adverse outcome marker worthy of screening.…”

“…7 Fewer than half of patients with isolated distal VTE were treated with any anticoagulants for 12 months in this study group. 7 The results shown by Yamashita et al 4 suggest that the reduction in thrombotic events conferred by longer OAC extends to populations from regions with low baseline VTE risk.…”

“…The diagnosis of isolated distal VTE is difficult to make in comparison with proximal VTE or pulmonary embolism. Indeed, Yamashita et al 4 reported that only ≈20% of patients objectively diagnosed with isolated distal VTE in their population were symptomatic at baseline. Distal VTE was identified through ultrasonographic screening in patients at high thrombotic risk within the active cancer cohort.…”

“…In this issue of Circulation, Yamashita et al 4 report the results of their open-label clinical trial that compared 12 months versus 3 months of therapeutic-dose edoxaban therapy in patients with active cancer found to have isolated distal venous thrombosis (below the knee). The investigators reported a reduced risk of the primary efficacy end point (symptomatic recurrence of VTE or VTErelated death) at 12 months in patients treated with 12 months of oral anticoagulation (OAC) as compared with participants treated for 3 months (Figure ).…”