12 Vs 3 Months of Edoxaban is Superior in Lowering Thrombotic Cancer Events

"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 patients [with cancer] with isolated distal DVT," according to Yugo Yamashita, MD.

Investigators reported that treatment with edoxaban (Lixiana) for 12 months appeared superior in decreasing thrombotic events vs a 3-month course in patients with active cancer who had newly diagnosed isolate distal deep vein thrombosis (DVT), according to a press release on findings from the ONCO DVT trial from the European Society of Cardiology.¹

Symptomatic recurrent venous thromboembolism (VTE) or VTE-related death events occurred in 1.0% of patients who received edoxaban for 12 months compared with 7.2% of patients who were treated for 3 months (odds ratio [OR], 0.13; 95% CI, 0.03-0.44).² Investigators also reported that major bleeding occurred in 9.5% vs 7.2% of patients, respectively (OR, 1.34; 95% CI, 0.75-2.41). The study’s outcomes were consistent regardless of age, body weight, and renal function.

“In patients [with cancer] 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,” principal investigator Yugo Yamashita, MD of Kyoto University, Japan said in the press release.¹ “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 patients [with cancer] with isolated distal DVT. We expect that the results will change practice and clinical guidelines in the cardio-oncology field.”

Although DVT is primary treated with anticoagulation agents, investigators have yet to determine an optimal strategy for those with isolated, distal DVT and cancer. The study marked the first randomized attempt to assess how treatment durations with Xa inhibitor edoxaban could affect outcomes in the aforementioned patient population. Moreover, investigators wanted to examine the prolonged regimen’s impact on bleeding events.

The multicenter, open-label, adjudicator-blinded superiority study included patients with active malignancies whose DVT was confirmed via compression ultrasonography. Patients who had treatment with an anticoagulation agent during trial randomization, an edoxaban counterindication, a life expectancy of 3 months or less, or pulmonary embolism were excluded from the study.

Investigators enrolled a total of 604 patients in 60 Japanese institutions between April 2019 and June 2022. Patients had an average age of 70.8 years, and most of the population were women (72%). The study included patients with cancer of the ovaries (14%), uterus (13%), lung (11%), colon (9%), pancreas (8%), stomach (5%), blood (5%), and breast (5%).

Those who enrolled were randomly assigned 1:1 to either the 12-month or 3-month arm. Patients were treated with either a 60 mg fixed dose of edoxaban or 30 mg in the case of those who had a creatinine clearance of 30 to 50 mL per minute or weight of 60 kg or lower, as well as those being treated with a concomitant P-glycoprotein inhibitor.

The study’s primary end point was symptomatic recurrent VTE or VTE-related mortality events at 12 months. Key secondary end points included major bleeding events at 12 months via International Society on Thrombosis and Haemostasis criteria.

These data read out at the 2023 European Society of Cardiology Congress.

References

1. 12 months of anticoagulation improves outcomes in cancer patients with minor blood clots. News release. European Society of Cardiology. August 28, 2023. Accessed September 1, 2023. https://bit.ly/3R4QGfs
2. Yamashita Y, Morimoto T, Muraoka N, et al. Edoxaban for 12 months versus 3 months in cancer patients with isolated distal deep vein thrombosis (ONCO DVT study): an open-label, multicenter, randomized clinical trial. Circulation. Published online August 28, 2023. doi:10.1161/CIRCULATIONAHA.123.066360