Researchers have found that 12 months of the oral factor Xa inhibitor edoxaban may be superior to 3 months for the reduction of thrombotic events in patients with cancer and distal deep vein thrombosis, according to new findings presented by Yamashita et al at the European Society of Cardiology Congress 2023.
Although the mainstay of treatment for deep vein thrombosis is anticoagulation therapy, optimal anticoagulation strategies for patients with cancer who have isolated distal deep vein thrombosis are not currently established.
Study Methods and Results
In the new multicenter, open-label, adjudicator-blinded, superiority ONCO DVT trial, the researchers randomly assigned 604 patients with active cancer and newly diagnosed isolated distal deep vein thrombosis to receive 60 mg of oral edoxaban once daily for either 12 or 3 months. The patients who had a creatinine clearance of 30 to 50 mL per minute, a body weight of 60 kg or less, or were receiving concomitant treatment with P-glycoprotein inhibitors received a lower dose of 30 mg once daily.
The average age of patients who participated in the trial was 70.8 years, and 72% (n = 433) of the patients identified as women. Among the patients, 14% of them had ovarian cancer; 13% had endometrial cancer; 11% had lung cancer; 9% had colorectal cancer; 8% had pancreatic cancer; and 5% each had gastric cancer, breast cancer, and hematologic malignancies.
The researchers confirmed the diagnosis of deep vein thrombosis with compression ultrasonography. Patients were excluded if they were taking anticoagulation therapy at the time of randomization, had a contraindication to edoxaban, were expected to have a prognosis of 3 months or less, or had a pulmonary embolism.
The primary endpoint of the trial was symptomatic recurrent venous thromboembolism or a venous thromboembolism–related death event at 12 months. The secondary endpoint was a major bleeding event defined according to the International Society on Thrombosis and Haemostasis criteria at 12 months.
The researchers discovered that the primary endpoint occurred in 1% (n = 3/296) of the patients in the 12-month edoxaban group and in 7.2% (n = 22/305) of those in the 3-month edoxaban group (odds ratio [OR] = 0.13, 95% confidence interval [CI] = 0.03–0.44). Further, major bleeding events occurred in 9.5% (n = 28/296) of the patients in the 12-month group and in 7.2% (n = 22/305) of those in the 3-month group (OR = 1.34, 95% CI = 0.75–2.41). The researchers reported that prespecified subgroup analyses according to age, body weight, and renal function did not affect the primary endpoint estimates.
Conclusions
“In patients [with cancer] with isolated distal [deep vein thrombosis], 12 months of edoxaban treatment was superior to 3 months with respect to the composite outcome of symptomatic recurrent [venous thromboembolism] or [venous thromboembolism]–related death with no difference in the rate of major bleeding,” underscored principal investigator Yugo Yamashita, MD, PhD, of the Kyoto University Graduate School of Medicine. “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 [this patient population]. We expect that the results will change practice and clinical guidelines in the cardio-oncology field,” he concluded.
