The influence of metastasis on clinical outcomes in patients with cancer-associated isolated distal deep vein thrombosis: A pre-specified subgroup analysis from the ONCO DVT study

BACKGROUND: The risk-benefit balance of extended anticoagulation in patients with metastatic cancer remains unclear. OBJECTIVES: This prespecified subgroup analysis aimed to evaluate the efficacy and safety of 12-and 3-month edoxaban treatment in patients with cancer-associated isolated distal deep vein thrombosis (DVT) based on cancer metastasis. METHODS: The ONCO DVT study, a randomized clinical trial, included 601 patients with cancer-associated isolated distal DVT, divided into metastasis (N = 147) and no metastasis subgroups (N = 454). The primary endpoint was symptomatic recurrent venous thromboembolism (VTE) or VTE-related death at 12 months, and the major secondary endpoint was major bleeding at 12 months. RESULTS: The cumulative incidence of the primary endpoint was lower in the 12-month edoxaban group than in the 3-month edoxaban group in both metastasis (3.2 % vs. 21.6 %, Log-rank P = 0.01) and no metastasis subgroups (0.5 % vs. 5.0 %, Log-rank P = 0.006). The cumulative incidence of the major secondary endpoint did not differ between the 2 groups in the metastasis subgroup (13.7 % vs. 16.2 %, Log-rank P = 0.42), but it was numerically higher in the 12-month group than in the 3-month group in the no metastasis subgroup (9.6 % vs. 4.7 %, Log-rank P = 0.051). CONCLUSIONS: Compared with 3-month edoxaban treatment, the 12-month treatment significantly reduced thrombotic risk in cancer-associated isolated distal DVT without increasing bleeding risk in patients with metastasis, suggesting that prolonged anticoagulation therapy had potential benefits for these patients. However, the bleeding risk was higher in the 12-month compared with 3-month edoxaban treatment in patients without metastasis.