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Rivaroxaban reduces risk for venous thromboembolism recurrence among patients with cancer
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ATLANTA —Patients with cancer at risk for recurrent venous thromboembolism appeared less likely to experience recurrence with rivaroxaban than dalteparin, according to results of a pilot study presented at the ASH Annual Meeting and Exposition.
Researchers observed a similar number of major bleeds among patients treated with rivaroxaban (Xarelto, Janssen) — a direct oral anticoagulant — than those treated with dalteparin, a form of low-molecular-weight heparin administered subcutaneously.
However, more clinically relevant nonmajor bleeds occurred in the rivaroxaban group.
VTE is an increasingly common yet often overlooked comorbidity for patients with cancer.
As many as 20% of patients with cancer develop VTE. Incidence is higher among those who are hospitalized, have metastatic disease, or undergo chemotherapy or surgery.
Limited research has been conducted to compare low-molecular-weight heparin with direct oral anticoagulants for treatment or prevention of VTE among patients with cancer.
Annie Young, PhD, professor of nursing at Warwick Medical School at University of Warwick in the United Kingdom, and colleagues conducted the prospective, randomized open-label Select-D trial to compare rivaroxaban — a highly selective direct factor Xa inhibitor — with dalteparin. Prior to trial initiation, dalteparin had been considered standard in the United Kingdom for extended treatment and prevention of acute VTE recurrence among patients with cancer.
The analysis included 406 patients (median age, 67 years; range, 22-87; 53% men; 95% white) recruited between October 2013 and December 2016 from 58 sites across the United Kingdom. All study participants had cancer (early or locally advanced disease, 38%; metastatic disease, 59%; hematologic malignancies, 3%) and VTE. More than half (53%) had incidental pulmonary embolism, and 47% had symptomatic pulmonary embolism or deep vein thrombosis.
The majority (69%) were receiving anticancer treatment at the time of VTE (chemotherapy, 83%; targeted therapy, 15%).
Researchers randomly assigned patients 1:1 to dalteparin — administered at 200 IU/kg daily in month 1, followed by 150 IU/kg in months 2 through 6) — or rivaroxaban, administered at 15 mg twice daily for 3 weeks, followed by 20 mg once daily until total treatment duration reached 6 months.
After 6 months of treatment, patients with DVT who were residual vein thrombosis positive as determined by compression ultrasound, as well as patients with pulmonary embolism at presentation, could be randomly assigned to rivaroxaban or placebo for an additional 6 months.
VTE recurrence served as the primary outcome measure. Secondary outcomes included major bleeds and clinically nonmajor bleeds — which included overt bleeds resulting in unscheduled contact with a physician, or discontinuation or interruption of the study drug — survival, acceptability and health economics.
At 6 months, researchers reported VTE recurrence rates of 11% (95% CI, 7-17) among patients assigned dalteparin and 4% (95% CI, 2-9) among patients assigned rivaroxaban.
Incidence of major bleeds was comparable among those assigned dalteparin (six bleeds among six patients [3%; 95% CI, 1-6]) and rivaroxaban (nine bleeds among eight patients [4%; 95% CI, 2-8]).
However, more clinically relevant nonmajor bleeds occurred in the rivaroxaban group (28 bleeds among 27 patients [13%; 95% CI, 9-19) than the dalteparin group (five bleeds among five patients [2%; 95% CI, 1-6]).
Three times as many patients assigned rivaroxaban (17%; n = 34) than dalteparin (5%; n = 11) experienced bleeds categorized as either major bleeds or clinically relevant nonmajor bleeds.
A similar percentage of patients in the rivaroxaban and dalteparin groups completed 6 months of trial treatment (54% vs. 52%). OS rates at 6 months were 74% (95% CI, 68-80) in the rivaroxaban group and 70% (95% CI, 63-76) in the dalteparin group.
“A large phase 3 trial will confirm the use of rivaroxaban for the treatment of VTE [among patients with cancer,” Young and colleagues wrote.
The second randomization closed due to high attrition rate, as only 92 of the 300 required patients were recruited. Reasons for patients not continuing to the second randomization included death or withdrawal (50%), being residual vein thrombosis negative (12%), failing other eligibility criteria (24%) or declining randomization (14%). – by Mark Leiser
For more information:
Young A, et al. Abstract 625. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2017; Atlanta.
Disclosures: Young reports honoraria from Bayer, Helsin and Leo Pharma, as well as research funding from Bayer. Please see the abstract for all other authors’ relevant financial disclosures.
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Alok A. Khorana, MD
This was a trial of patients with active cancer and newly diagnosed VTE for whom the standard of care is low-molecular-weight heparin therapy for 6 months.
In this study, researchers randomly assigned patients to a direct oral anticoagulant, rivaroxaban, or dalteparin for 6 months. Overall, the study results were encouraging. Rivaroxaban appeared associated with a substantially lower rate of recurrent VTE than dalteparin (4% v 11%), but bleeding risk was somewhat higher. Fatal bleeds were similar in both groups, and survival also was similar.
Based on these findings, along with known issues related to adherence and cost for low-molecular-weight heparins, this study — taken in context with the edoxaban (Savaysa, Daiichi-Sankyo) randomized trial, which had similar results — direct oral anticoagulants can now be considered one of the first-line options for treatment of cancer-associated thrombosis.
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