TY - JOUR
T1 - Rivaroxaban for thromboprophylaxis in high-risk ambulatory patients with cancer
AU - CASSINI Investigators
AU - Khorana, Alok A.
AU - Soff, Gerald A.
AU - Kakkar, Ajay K.
AU - Vadhan-Raj, Saroj
AU - Riess, Hanno
AU - Wun, Ted
AU - Streiff, Michael B.
AU - Garcia, David A.
AU - Liebman, Howard A.
AU - Belani, Chandra P.
AU - O'Reilly, Eileen M.
AU - Patel, Jai N.
AU - Yimer, Habte A.
AU - Wildgoose, Peter
AU - Burton, Paul
AU - Vijapurkar, Ujjwala
AU - Kaul, Simrati
AU - Eikelboom, John
AU - McBane, Robert
AU - Bauer, Kenneth A.
AU - Kuderer, Nicole M.
AU - Lyman, Gary H.
N1 - Funding Information:
The trial was designed by members of the steering committee, with input regarding end-point selection and statistical analysis from regulatory authorities, and was cosponsored by Janssen and Bayer. The steering committee provided oversight of trial conduct and data reporting. Data were collected by Janssen and analyzed in collaboration with steering committee members. No Janssen employees were members of the steering committee or the data and safety monitoring board. All the authors had access to all the data and contributed to the interpretation of results. The first author wrote the initial draft of the manuscript, and all the authors contributed to revisions, with no conceptual contributions from anyone who was not an author and with no other writing assistance. Assistance in formatting the manuscript and preparing the files for submission was provided by two medical writers and funded by Janssen. All the authors vouch for the accuracy and completeness of the data reported and for the adherence of the trial to the protocol.
Funding Information:
Supported by Janssen, Bayer, and the Sondra and Stephen Hardis Chair in Oncology Research (to Dr. Khorana), by grants (U01HL143402 and R34 HL127156, to Dr. Khorana) from the National Heart, Lung, and Blood Institute, and by the Cleveland Clinic Center of Excellence for Cancer-Associated Thrombosis (to Dr. Khorana) and the Porter Family Fund (to Dr. Khorana).
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
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U2 - 10.1056/NEJMoa1814630
DO - 10.1056/NEJMoa1814630
M3 - Article
C2 - 30786186
AN - SCOPUS:85061961689
VL - 380
SP - 720
EP - 728
JO - New England Journal of Medicine
JF - New England Journal of Medicine
SN - 0028-4793
IS - 8
ER -