Rivaroxaban for thromboprophylaxis in high-risk ambulatory patients with cancer Journal Article


Authors: Khorana, A. A.; Soff, G. A.; Kakkar, A. K.; Vadhan-Raj, S.; Riess, H.; Wun, T.; Streiff, M. B.; Garcia, D. A.; Liebman, H. A.; Belani, C. P.; O'Reilly, E. M.; Patel, J. N.; Yimer, H. A.; Wildgoose, P.; Burton, P.; Vijapurkar, U.; Kaul, S.; Eikelboom, J.; McBane, R.; Bauer, K. A.; Kuderer, N. M.; Lyman, G. H.; for the CASSINI Investigators
Article Title: Rivaroxaban for thromboprophylaxis in high-risk ambulatory patients with cancer
Abstract: BACKGROUND Ambulatory patients receiving systemic cancer therapy are at varying risk for venous thromboembolism. However, the benefit of thromboprophylaxis in these patients is uncertain. METHODS In 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 deep-vein 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. RESULTS Of 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). CONCLUSIONS In 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. © 2019 Massachusetts Medical Society.
Keywords: adult; controlled study; treatment outcome; aged; aged, 80 and over; middle aged; clinical trial; antineoplastic agents; antineoplastic agent; neoplasm; neoplasms; bleeding; randomized controlled trial; incidence; risk factors; risk factor; phase 3 clinical trial; kaplan meier method; double blind procedure; double-blind method; administration, oral; venous thromboembolism; rivaroxaban; oral drug administration; kaplan-meier estimate; complication; hemorrhage; blood clotting factor 10a inhibitor; very elderly; intention to treat analysis; humans; human; male; female; chemically induced; factor xa inhibitors
Journal Title: New England Journal of Medicine
Volume: 380
Issue: 8
ISSN: 0028-4793
Publisher: Massachusetts Medical Society  
Date Published: 2019-02-21
Start Page: 720
End Page: 728
Language: English
DOI: 10.1056/NEJMoa1814630
PUBMED: 30786186
PROVIDER: scopus
DOI/URL:
Notes: Source: Scopus
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MSK Authors
  1. Eileen O'Reilly
    524 O'Reilly
  2. Gerald A Soff
    86 Soff