Rivaroxaban for Thromboprophylaxis in High-Risk Ambulatory Patients with Cancer

Abstract

BACKGROUNDAmbulatory patients receiving systemic cancer therapy are at varying risk for venous thromboembolism. However, the benefit of thromboprophylaxis in these patients is uncertain. METHODSIn this double-blind, randomized trial involving high-risk ambulatory patients with cancer (Khorana score of ≥2, on a scale from 0 to 6, with higher scores indicating a higher risk of venous thromboembolism), we randomly assigned patients without deep-vein thrombosis at screening to receive rivaroxaban (at a dose of 10 mg) or placebo daily for up to 180 days, with screening every 8 weeks. The primary efficacy end point was a composite of objectively confirmed proximal deep-vein thrombosis in a lower limb, pulmonary embolism, symptomatic deepvein thrombosis in an upper limb or distal deep-vein thrombosis in a lower limb, and death from venous thromboembolism and was assessed up to day 180. In a prespecified supportive analysis involving the same population, the same end point was assessed during the intervention period (first receipt of trial agent to last dose plus 2 days). The primary safety end point was major bleeding. RESULTSOf 1080 enrolled patients, 49 (4.5%) had thrombosis at screening and did not undergo randomization. Of the 841 patients who underwent randomization, the primary end point occurred in 25 of 420 patients (6.0%) in the rivaroxaban group and in 37 of 421 (8.8%) in the placebo group (hazard ratio, 0.66; 95% confidence interval [CI], 0.40 to 1.09; P = 0.10) in the period up to day 180. In the prespecified intervention-period analysis, the primary end point occurred in 11 patients (2.6%) in the rivaroxaban group and in 27 (6.4%) in the placebo group (hazard ratio, 0.40; 95% CI, 0.20 to 0.80). Major bleeding occurred in 8 of 405 patients (2.0%) in the rivaroxaban group and in 4 of 404 (1.0%) in the placebo group (hazard ratio, 1.96; 95% CI, 0.59 to 6.49). CONCLUSIONSIn high-risk ambulatory patients with cancer, treatment with rivaroxaban did not result in a significantly lower incidence of venous thromboembolism or death due to venous thromboembolism in the 180-day trial period. During the intervention period, rivaroxaban led to a substantially lower incidence of such events, with a low incidence of major bleeding. (Funded by Janssen and others; CASSINI ClinicalTrials .gov number, NCT02555878.

Direct oral anticoagulant for the prevention of thrombosis in ambulatory patients with cancer: A systematic review and meta‐analysis

“…The RCT compared 291 patients assigned to apixaban 2.5 mg twice daily vs 283 patients on placebo and reported symptomatic or incidental VTE outcome at 6 months. The CASSINI trial (international including the United States) enrolled adult patients with active cancer who were initiating new systemic therapy and had a Khorana score of 2 or higher . The median age was 63, and 51% were male.…”

Risk factors for cancer‐associated venous thromboembolism: The venous thromboembolism prevention in the ambulatory cancer clinic (VTE‐PACC) study

“…Over time, VTE risk assessment at baseline may become less relevant for patients, but assessing dynamic risk factors such as hospitalization (demonstrated here), chemotherapy choice, or performance status may become more important. Two randomized trials were recently published using the Khorana score to risk stratify cancer patients for pharmacologic thromboprophylaxis . These trials demonstrated a modest benefit in VTE reduction at the expense of increased bleeding.…”

The use of direct oral anticoagulants for primary thromboprophylaxis in ambulatory cancer patients: Guidance from the SSC of the ISTH

“…DOACs have the advantage of oral administration without requiring intense laboratory monitoring. Apixaban for the Prevention of Venous Thromboembolism in High‐Risk Ambulatory Cancer Patients (AVERT) and CASSINI studies evaluated their benefit for primary VTE prophylaxis in intermediate to high‐risk ambulatory cancer patients …”

“…Both studies incorporated the Khorana score to target intermediate to high‐risk patients. AVERT used apixaban, whereas CASSINI used rivaroxaban for thromboprophylaxis …”

“…CASSINI study was a randomized, placebo‐controlled, double‐blinded clinical trial in 841 ambulatory cancer patients with locally advanced or metastatic disease with Khorana score ≥2 starting a new systemic therapy regimen, to assess the efficacy and safety of rivaroxaban in the primary prevention of VTE . Patients were randomized to rivaroxaban 10 mg once daily versus placebo.…”