A Multicenter, Prospective Study on the PK/PD/PGx Analysis of Direct Oral Anticoagulants in Cancer Patients with Venous Thromboembolism

Abstract

Venous thromboembolism (VTE) is a common complication occurring in patients with cancer, significantly affecting prognosis. Although the efficacy of direct oral anticoagulants, including edoxaban, for treating cancer-associated VTE has been demonstrated, Japanese patients often experience bleeding when administered standard doses. Conversely, dose reduction may compromise the efficacy, making dose adjustment challenging. We prospectively analyzed the relationship between edoxaban plasma trough concentrations and bleeding events or therapeutic efficacy in cancer patients with VTE. We included cancer patients diagnosed with VTE and treated with edoxaban at the Shiga University of Medical Science Hospital and Kyoto University Hospital between April 2022 and December 2024. Edoxaban concentrations were measured using liquid chromatography-tandem mass spectrometry. Major bleeding and clinically relevant non-major bleeding (CRNMB) were assessed using ISTH criteria. Efficacy was evaluated using an imaging-based assessment of the thrombus size. Eleven patients (median age: 72 years) were included; nine patients received 60 mg/day, and two received 30 mg/day. Cancer types included lung (three patients), uterine (two patients), ovarian, bladder, gastric, pancreatic, intrahepatic cholangiocarcinoma, and melanoma (one patient each). Five patients had metastatic disease, and nine received chemotherapy. The VTE types included pulmonary embolism (eight patients) and deep vein thrombosis (six patients), with overlap in three cases. Median trough edoxaban concentrations were higher in patients with major bleeding than those without (32.6 vs. 13.5 ng/mL, P = 0.200). Among the seven patients assessed for efficacy, the concentration was 50.3 ng/mL in the case with no change in thrombus (one patient), 29.7 ng/mL in the case with thrombus improvement (one patient), and a median of 13.4 ng/mL (range: 9.3-223.7 ng/mL) in cases with thrombus disappeared (five patients). The measurement of edoxaban concentrations may help predict major bleeding in cancer patients with VTE. However, owing to the small sample size and preliminary nature of this study, further investigation is warranted.