Rivaroxaban Versus Apixaban for Treatment of Cancer-Associated Venous Thromboembolism: A Head-to-Head Analysis of the United States Cohort of the Observational Study in Cancer-Associated Thrombosis for Rivaroxaban: (H2H-OSCAR-US)

BACKGROUND: No head-to-head randomized trials of rivaroxaban vs apixaban for the treatment of cancer-associated thrombosis (CAT) have been published. We sought to assess whether rivaroxaban was associated with comparable effectiveness and safety as apixaban for CAT treatment in patients with an active cancer type in which direct-acting oral anticoagulant (DOAC) therapy is not associated with a high risk of bleeding.

METHODS: This retrospective study used US Optum De-Identified electronic health data from January 1, 2013 to December 31, 2020. To be included, patients had to be >18 years old, diagnosed with active (primary or metastatic) cancer excluding esophageal, gastric, unresected colorectal, bladder, leukemia, or central nervous system cancers (except brain cancer, which was included) (ie, a cohort of patients with CAT for whom DOACs are endorsed by guidelines as alternatives to low molecular weight heparin); experienced a hospital, emergency department or observation unit admission for venous thromboembolism (VTE); received a therapeutic VTE dose of rivaroxaban or apixaban, and was on rivaroxaban or apixaban on day 7 after the qualifying VTE; and were actively recorded in the data set ≥12 months prior to experiencing CAT. Active cancer was defined as cancer being actively treated, diagnosed within 6 months prior to the index CAT, or associated with metastatic disease regardless of time from cancer diagnosis. Patients were excluded if they had an alternative indication for anticoagulation, were anticoagulated in the 12 months prior, or were pregnant. The study was powered to assess the time to first composite event of recurrent VTE or any bleeding resulting in hospitalization at a maximum follow up of 3 months. Other outcomes assessed included the composite of recurrent VTE or any critical organ bleeding, recurrent VTE, any bleeding resulting in hospitalization, and any critical organ bleeding at 3 and 6 months. Stabilized inverse probability of treatment weighting (IPTW) was used to balance anticoagulant cohorts for baseline covariates. Hazard ratios (HRs) with 95% confidence intervals (CIs) for all outcomes were calculated using Cox regression with robust estimators. A priori, we calculated 958 patients/group were needed to demonstrate non-inferiority of rivaroxaban for the composite of recurrent VTE or any bleeding resulting in hospitalization with 80% power, assuming an incidence rate of 7% in both groups and an upper limit of the 95% CI for non-inferiority of 1.50 (previously used in the in the HOKUSAI VTE Cancer trial).

RESULTS: We identified a total of 2437 patients (1344 apixaban and 1093 rivaroxaban). Of these, 29.0% were ≥75 years old, 56.9% were female, 20.6% had a body mass index ≥35 kg/m², and 19.4% had an estimated glomerular filtration rate <60 mL/min at baseline. The CAT event was a pulmonary embolism ± deep vein thrombosis in 45.6% of patients, 37.8% had metastatic disease, and 57.8% received active cancer treatment within 4 weeks of the CAT event. The most common cancer types (>10% prevalence) included breast (23.5%), lung (20.1%), prostate (14.9%), and hepatobiliary (12.1%). After IPTW, characteristics of patients receiving rivaroxaban and apixaban were similar for all covariates included in the propensity score model (absolute standardized difference ≤0.07 for all). At 3 months, rivaroxaban was found to be at least as effective and safe as apixaban for the composite of recurrent VTE or bleeding-related hospitalization (5.3% versus 6.0%; HR=0.87, 95% CI 0.60-1.27)(Figure). No significant differences were observed between groups for this outcome at 6 months or for other outcomes at 3 or 6 months.

CONCLUSIONS: Rivaroxaban appeared to be at least as effective and safe as apixaban, with non-inferiority demonstrated for the composite outcome of recurrent VTE or any bleeding resulting in hospitalization at 3 months. No statistical difference in any other outcome was observed after 3 or 6 months of follow up.

Abdelgawwad:Bayer AG: Current Employment. Psaroudakis:Bayer AG: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company. Rivera:Bayer Hispania, S.L.: Current Employment. Brobert:Bayer AB: Ended employment in the past 24 months; Bayer AG: Consultancy. Cohen:Alexion/Astra Zeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; Bayer AG: Consultancy, Honoraria, Speakers Bureau; BMS/Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau. Khorana:Janssen: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; Anthos: Consultancy, Honoraria; sanofi: Consultancy, Honoraria. Becattini:BMS: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Bayer AG: Consultancy, Honoraria. Lee:Bayer AG: Consultancy, Honoraria; LEO Pharma: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Servier: Consultancy; BMS: Honoraria. Carrier:Sanofi: Consultancy; Pfizer: Consultancy, Honoraria, Research Funding; Leo Pharma: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Servier: Consultancy, Honoraria. Coleman:Bayer AG: Consultancy, Honoraria, Other: Support for attending meetings and/or travel, Research Funding; Alexion Pharmaceuticals: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Medscape: Honoraria, Speakers Bureau.