Key Points:
- The optimal duration of therapy for distal deep vein thrombosis (DVT) among patients with an active malignancy is unknown.
- ONCO-DVT was the first randomized controlled trial comparing 12-months to 3-months of Edoxaban in patients with an active malignancy and recently diagnosed distal DVT
- Treatment with Edoxaban for 12 months compared to 3 months reduced symptomatic recurrent venous thromboembolism (VTE) or VTE-related death events without significantly increasing major bleeding risk.
Compared with the general population, patients with cancer are at an increased risk of not only developing incident venous thromboembolism (VTE) but also recurrent VTE events associated with increased morbidity and mortality. In recent times, direct oral anticoagulants, particularly direct factor Xa inhibitors like Edoxaban, have become an effective, safe, and more convenient alternative for managing acute VTEs compared to low molecular weight heparin, which had been the standard of care for many years. However, the optimal duration of therapy among patients with cancer and distal DVT remains unclear. To address this knowledge gap, Dr. Yugo Yamashita from Kyoto University, Japan, presented the “Optimal Duration of Anticoagulation Therapy for Isolated Distal Deep Vein Thrombosis in Patients With Cancer Study”, or the ONCO-DVT study, in a hotline session at ESC 2023, along with a simultaneous publication in Circulation.
The ONCO-DVT study (NCT03895502) marked the first multicenter, open-label, adjudicator-blinded, superiority trial that compared 12 months to 3 months of Edoxaban in patients with active malignancy and a recent diagnosis of isolated distal DVT. Enrolling patients from 60 institutions across Japan, the trial excluded patients with a pulmonary embolism, on an anticoagulant, who had contraindications to Edoxaban, or those with a life expectancy of under 3 months. These participants were then randomly assigned in a 1:1 fashion to either 12 months or 3 months of Edoxaban. The doses of Edoxaban were 60 mg daily or 30 mg daily if patients met certain criteria such as creatinine clearance of 30-50 mL/minute, body weight of 60 kg or less, or concurrent use of a P-glycoprotein inhibitor. The primary endpoint was the occurrence of symptomatic recurrent VTE or VTE-related death events at the 12-month mark, while the secondary endpoint was major bleeding events defined per the International Society on Thrombosis and Hemostasis (ISTH) criteria at 12 months.
In total, the study included 604 patients with an average age of 70.8 years, of whom 72% were women. The most prevalent cancer types were ovarian, uterine, and lung. Notably, patients in the 12-month group experienced a significant reduction in the primary endpoint of symptomatic recurrent VTE or VTE-related death when compared to those in the 3-month Edoxaban group (OR 0.13; 95% CI 0.03 to 0.44). However, there was no discrepancy in the secondary endpoint of major bleeding between the two groups (9.5% vs 7.2% respectively, OR, 1.34; 95% CI, 0.75 to 2.41). Prespecified subgroup analyses according to age, body weight and renal function did not affect the estimates on the primary endpoint.
Principal investigator Dr. Yugo Yamashita stated “In cancer patients with isolated distal DVT, 12 months of Edoxaban treatment was superior to 3 months with respect to the composite outcome of symptomatic recurrent VTE or VTE-related death with no difference in the rate of major bleeding. This is the first and only randomized trial to show the superiority of longer duration over shorter duration of anticoagulation therapy for reducing thrombotic events in cancer patients with isolated distal DVT. We expect that the results will change practice and clinical guidelines in the cardio-oncology field.”
