Treatment and outcomes after on-treatment recurrent venous thromboembolism in patients with cancer: a post hoc analysis of the Hokusai venous thromboembolism cancer study

Background: The management of recurrent venous thromboembolism (VTE) despite anticoagulant treatment in patients with cancer is uncertain. To address this, we used data from the Hokusai VTE Cancer trial, which compared edoxaban with dalteparin to treat cancer-associated VTE. Objectives: To characterize and evaluate anticoagulant treatment strategies during and after on-treatment recurrent VTE, including the type and dose of anticoagulant. Methods: In this post hoc analysis, all patients with adjudicated on-treatment recurrent VTE within 12 months after randomization were included. Outcomes were second recurrent VTE and major bleeding within 3 months after the first recurrent VTE. Results: A total of 67 patients developed on-treatment recurrent VTE while receiving therapeutic-dose edoxaban (31%), therapeutic-dose low-molecular-weight heparin (LMWH) (34%), maintenance-dose LMWH (21%), or other therapies (14%). After the recurrent event, 28 patients (42%) received an increased dose, 35 (52%) a comparable dose, and 4 (6%) a reduced dose or stopped anticoagulants. Common treatment regimens included supratherapeutic-dose LMWH (21%), therapeutic-dose LMWH (51%), direct oral anticoagulants (16%), or another treatment strategy (12%). In the 3 months after recurrent VTE, 6 (9%) patients had a second recurrence and 7 (10%) had major bleeding. Conclusion: Treatment strategies for recurrent VTE in patients with cancer are heterogeneous. The risk of a second recurrence and major bleeding are considerable. More studies are needed to determine the optimal treatment strategy for recurrent cancer-associated thrombosis.