Efficacy and safety of prolonged edoxaban treatment for gastrointestinal cancer patients with isolated distal deep vein thrombosis: insight from the ONCO DVT study

Abstract Background Patients with gastrointestinal (GI) cancer could be at a high risk of bleeding with anticoagulation therapy of direct oral anticoagulants. The ONCO DVT study (NCT03895502) revealed that 12-month edoxaban treatment for cancer patients with isolated distal deep vein thrombosis (DVT) reduced a composite outcome of a symptomatic recurrent venous thromboembolism (VTE) or VTE-related death compared with 3-month edoxaban treatment. However, it has been still uncertain whether these results are applicable to patients with GI cancer. Purpose The purpose of this post-hoc subgroup analysis was to evaluate the efficacy and safety of 12-month edoxaban treatment for GI cancer patients. Methods The ONCO DVT study was a randomized clinical trial which randomly assigned cancer patients with isolated distal DVT to receive either 12-month or 3-month edoxaban treatment in a 1-to-1 ratio and evaluated clinical outcomes at 12 months. In the current study, 601 patients were stratified into the GI cancer (N=102) and non-GI cancer (N=499) subgroups. GI cancer was defined as esophageal, gastric, duodenal, small intestinal, cecal or colon cancer. The primary endpoint was a composite outcome of a symptomatic recurrent VTE or VTE-related death at 12 months. The major secondary endpoint was major bleeding at 12 months. Results Patients with GI cancer were older (73.4 vs. 70.3 years, P=0.004) and more often men (38% vs. 26%, P=0.01) compared with those without, whereas there was no significant difference in body weight, symptoms at baseline, site of thrombus, or dosing of edoxaban between the 2 subgroups. There was also no significant difference in cancer status including metastatic disease. In the GI cancer subgroup, the primary endpoint did not occur in the 12-month edoxaban group, and occurred in 3 of 53 (5.7%) patients in the 3-month edoxaban group, whereas in the non-GI cancer subgroup, the primary endpoint occurred in 3 of 247 (1.3%) patients in the 12-month edoxaban group, and in 19 of 252 (7.5%) patients in the 3-month edoxaban group (OR 0.15; 95% CI 0.04–0.45). There was no significant interaction in the primary endpoint (P interaction=0.38). In the GI cancer subgroup, the major secondary endpoint occurred in 3 of 49 (6.1%) patients in the 12-month edoxaban group, and in 4 of 53 (7.6%) patients in the 3-month edoxaban group (OR 0.80; 95% CI 0.15–3.81), whereas in the non-GI cancer subgroup, the major secondary endpoint occurred in 25 of 247 (10.1%) patients in the 12-month edoxaban group, and in 18 of 252 (7.1%) patients in the 3-month edoxaban group (OR 1.46; 95% CI 0.78–2.79). There was also no significant interaction in the major secondary endpoint (P interaction=0.48). Conclusions In patients with cancer-associated isolated distal DVT, patients with GI cancer did not show a signal of an increased risk of major bleeding with prolonged anticoagulation therapy of edoxaban.