Introduction: Venous thromboembolism (VTE) affects ~20% of patients with cancer prior to death and may be present in up to half of cancer patients upon autopsy. International Society of Thrombosis and Haemostasis (ISTH) guidelines recommend oral factor Xa inhibitors for the acute treatment and secondary prevention of cancer-associated thrombosis (CAT) in patients considered low risk of bleeding and without a potential for drug-drug interactions with current systemic therapy. We sought to evaluate the effectiveness and safety of rivaroxaban versus a low molecular weight heparin (LMWH) for the treatment of CAT in routine practice.
Methods: Using United States Surveillance, Epidemiology and End Results (SEER)-Medicare-linked data from 2013 to 2015, we identified adults diagnosed with lung, breast, pancreatic, prostate or ovarian cancer, having at ≥1 hospitalization or emergency department admission (index event) with a primary discharge diagnosis code for VTE (indicating VTE was the foremost reason for admission) , ≥12-months of continuous medical and prescription benefits prior to the index CAT and who received rivaroxaban or a LMWH as their first outpatient anticoagulant. Patients with primary or metastatic gastrointestinal cancers, stage 4 or worse chronic kidney disease or liver failure were excluded. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the composite outcome of recurrent VTE or major bleeding, each of these outcomes alone as well as all-cause mortality in the subsequent 12-months were calculated using a multivariable Fine-Gray (competing risk) Cox regression model adjusted for baseline covariates and propensity score decile (c-index=0.76) estimated using generalized boosted models on the basis of 10,000 regression trees.
Results: We included 259 rivaroxaban- and 559 LMWH-managed patients with CAT. The median age (25%, 75% range) of patients was 73 (68, 79) years, 62.5% were men and 43.6% had pulmonary embolism. The incident cancer diagnosis was made between 2010 and 2013 in 87.8% of patients. Primary cancer locations included lung (41.8%), breast (21.8%), pancreatic (12.1%), prostate (11.9%), ovarian (5.3%) and other (7.1%). Nearly all patients (96.5%) were diagnosed with stage 2 or 3 disease. During the 12-month follow-up period, the incidence of the composite of recurrent VTE or major bleeding was 13.8%, recurrent VTE alone occurred in 11.4% and major bleeding alone in 2.9% of patients and all-cause mortality occurred in 48.4%. No significant difference in patients' relative hazard of the experiencing the composite outcome (HR=0.86, 95%CI=0.52-1.41), recurrent VTE (HR=0.91, 95%CI=0.51-1.62), major bleeding (HR=0.90, 95%CI=0.29-2.83) or all-cause mortality (HR=0.86, 95%CI=0.62-1.21) were observed between the rivaroxaban and LMWH-managed cohorts.
Conclusions: In this real-world study of rivaroxaban- and LMWH-managed CAT patients, no significant difference in patients' relative hazard of experiencing the composite outcome, recurrent thrombosis, major bleeding or all-cause mortality were observed between the two cohorts. These data are consistent with recommendation that the oral factor Xa inhibitor, rivaroxaban, is a reasonable alternative to LMWH for the treatment of CAT and prevention of recurrent thrombosis.
Lyman:Amgen Inc.: Other: Research support, Research Funding; Janssen Scientific Affairs, LLC: Research Funding; Generex Biotechnology: Membership on an entity's Board of Directors or advisory committees; G1 Therapeutics, Halozyme Therapeutics, Partners Healthcare, Hexal, Bristol-Myers Squibb, Helsinn Therapeutics, Amgen Inc., Pfizer, Agendia, Genomic Health, Inc.: Consultancy. Kuderer:Mylan: Consultancy, Other: Travel, Accommodations, Expenses; Celldex: Consultancy; Myriad Genetics: Consultancy; Coherus Biosciences: Consultancy, Other: Travel, Accommodations, Expenses; Pfizer: Consultancy; Halozyme: Consultancy; Janssen Scientific Affairs, LLC: Consultancy, Other: Travel, Accommodations, Expenses. Coleman:Bayer AG: Consultancy, Honoraria, Research Funding; Janssen Scientific Affairs LLC: Consultancy, Honoraria, Research Funding.
Asterisk with author names denotes non-ASH members.