Extended Rivaroxaban Therapy for Cancer-Associated Low-Risk Pulmonary Embolism by Chemotherapy Status: Insights from the ONCO PE Trial

The ONCO PE trial demonstrated the superiority of 18-month compared with 6-month rivaroxaban treatment for cancer-associated acute low-risk pulmonary embolism (PE) in reducing recurrent venous thromboembolism (VTE). However, it was uncertain whether the results could be applicable to patients in different stages of chemotherapy exposure. In this prespecified subgroup analysis of the ONCO PE trial, patients were classified into chemotherapy (n = 107) and nonchemotherapy (n = 71) subgroups based on the status of chemotherapy exposure at the PE diagnosis. We compared the primary endpoint of recurrent VTE and the major secondary endpoint of major bleeding between the 18- and 6-month rivaroxaban treatment groups in each subgroup. The cumulative 18-month incidence rate of recurrent VTE was numerically lower in the 18-month rivaroxaban group than in the 6-month rivaroxaban group among both the chemotherapy (6.6% vs. 20.8%, log-rank p = 0.06) and nonchemotherapy subgroups (6.6% vs. 23.4%, log-rank p = 0.09) without a significant interaction between chemotherapy exposure and treatment duration (p-interaction = 0.94). There was no significant difference in the cumulative 18-month incidence of major bleeding between the 18- and 6-month rivaroxaban groups among either the chemotherapy (9.7% vs. 4.1%, log-rank p = 0.29) or nonchemotherapy subgroup (6.2% vs. 8.0%, log-rank p = 0.73) without a significant interaction between chemotherapy exposure and treatment duration (p-interaction = 0.36). Extended anticoagulation therapy for patients with cancer-associated acute low-risk PE might have a potential benefit in reducing thrombotic risk irrespective of the status of chemotherapy exposure without a significantly increased risk of major bleeding.