Evaluating the incidence of thrombosis in patients with concurrent second-generation androgen receptor inhibitor therapy and direct oral anticoagulants: A retrospective chart review.

[INTRODUCTION] Many patients with prostate cancer have an indication for anticoagulation. This presents a pharmacokinetic dilemma as enzalutamide and apalutamide have significant effects on the metabolism of direct oral anticoagulants. To date, data on coadministration of these agents is limited to pharmacokinetic studies and post-hoc analysis, which suggest no deleterious effects. Our study seeks to elucidate whether the concomitant administration of enzalutamide or apalutamide with apixaban or rivaroxaban results in a clinically meaningful change in thromboembolic events.

[METHODS] We conducted a retrospective, observational cohort study of adult prostate cancer patients on concomitant apalutamide or enzalutamide and apixaban or rivaroxaban for ≥ 3 months from January 1, 2018 to August 9, 2024 at all 3 tertiary sites of our care network. The primary outcome was incidence of deep vein thrombosis, pulmonary embolism, or ischemic stroke. The secondary outcomes included the incidence of switching of anticoagulant therapy or prostate-directed therapy due to concern for drug-drug interaction. The secondary outcomes were assessed in the entire cohort without exclusion.

[RESULTS] A total of 500 patients were assessed for eligibility, of which 94 were included in the final analysis of primary outcome. The primary outcome occurred in 4 patients (4.3%). The switching of anticoagulant therapy occurred in 32 patients (6.4%). The switching of prostate-directed therapy occurred in 5 patients (1%).

[CONCLUSION] This study suggests that there is not an increased incidence of VTE or stroke when compared to historical controls. This study may help clinicians make risk benefit decisions regarding concurrent therapies.