Background
Pulmonary embolism (PE) represents a major cause of morbidity and mortality in patients with cancer due to their heightened prothrombotic state. Proper anticoagulation is critical to prevent recurrent venous thromboembolism (VTE), but the optimal duration for anticoagulation in cancer-associated acute low-risk PE remains unclear. Extending anticoagulation might reduce recurrent thrombotic events but raises concerns about increased bleeding, especially in a vulnerable oncologic population. This clinical equipoise underpins the ONCO PE trial conducted in Japan, evaluating rivaroxaban treatment duration in this patient group.
Study Design
The ONCO PE trial was a multicenter, open-label, randomized clinical trial with blinded adjudication involving 32 Japanese institutions. It enrolled patients with active cancer diagnosed with acute low-risk PE, specifically with a simplified Pulmonary Embolism Severity Index (sPESI) score of 1. Participants were randomized 1:1 to receive oral rivaroxaban anticoagulation for either 18 months or 6 months. The primary endpoint was recurrent VTE at 18 months, assessed via clinical and imaging criteria. The major secondary endpoint was major bleeding, defined per the International Society on Thrombosis and Hemostasis standards. The trial was designed to test the superiority of the extended 18-month course over the 6-month regimen in preventing recurrent thrombotic events.
Key Findings
Between February 2021 and March 2023, 179 patients were randomized; however, one withdrew consent, leaving 178 patients for intention-to-treat analysis. Baseline characteristics were comparable between both groups: mean age 65.7 years, 47% male, and 12% symptomatic at presentation. Notably, the 18-month rivaroxaban group experienced a significantly lower rate of recurrent VTE (5.6%, 5/89) compared to the 6-month group (19.1%, 17/89), with an odds ratio (OR) of 0.25 (95% CI 0.09–0.72; P=0.01). Among 22 recurrent VTEs, 5 were symptomatic; 11 were recurrent PEs, including severe cases with main and lobar involvement; 11 were recurrent deep vein thromboses (DVT), including proximal DVT.
Regarding safety, major bleeding events were numerically higher in the extended-treatment group (7.8% vs. 5.6%; OR 1.43, 95% CI 0.44–4.70; P=0.55), though the difference was not statistically significant. These data suggest that prolonged rivaroxaban reduces VTE recurrence without a significant increase in major bleeding.
Kaplan-Meier curves for the first persistent rivaroxaban discontinuation.
Expert Commentary
The ONCO PE trial provides robust evidence supporting extended anticoagulation in cancer patients with low-risk PE. Previous guidelines often extrapolated data from non-cancer populations or shorter treatment durations, leaving a gap in evidence for management tailored to oncology patients at low PE risk. The striking reduction in recurrent VTE underscores the biological plausibility that ongoing cancer-related hypercoagulability persists beyond 6 months, necessitating longer therapy.
While bleeding risks did not reach significance, the observed trend warrants individualized clinical judgment, weighing bleeding risk factors such as tumor type, thrombocytopenia, or concomitant therapies. Open-label design and geographic homogeneity may limit generalizability, but blinded adjudication strengthens outcome validity.
Future research might explore biomarkers for risk stratification to personalize anticoagulation duration further and evaluate direct comparisons with other direct oral anticoagulants or low molecular weight heparins in this setting.
Conclusion
For patients with cancer-associated acute low-risk PE, extending rivaroxaban therapy to 18 months significantly reduces recurrent VTE compared to a 6-month regimen, without a statistically significant increase in major bleeding. These findings fill a critical evidence gap and may inform guideline updates and personalized management strategies aimed at improving thrombotic event prevention while maintaining safety in this vulnerable population.
References
Yamashita Y, Morimoto T, Muraoka N, et al; ONCO PE Trial Investigators. Rivaroxaban for 18 Months Versus 6 Months in Patients With Cancer and Acute Low-Risk Pulmonary Embolism: An Open-Label, Multicenter, Randomized Clinical Trial (ONCO PE Trial). Circulation. 2025;151(9):589-600. doi:10.1161/CIRCULATIONAHA.124.072758 IF: 38.6 Q1 . PMID: 39556015 IF: 38.6 Q1 ; PMCID: PMC11875411 IF: 38.6 Q1 .
ClinicalTrials.gov. Identifier: NCT04724460.
