Rivaroxaban for thromboprophylaxis in high-risk ambulatory patients with cancer

CASSINI Investigators

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)720-728
Number of pages9
JournalNew England Journal of Medicine
Volume380
Issue number8
DOIs
StatePublished - Jan 1 2019

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Venous Thromboembolism
Neoplasms
Venous Thrombosis
Placebos
Confidence Intervals
Hemorrhage
Random Allocation
Lower Extremity
Incidence
Rivaroxaban
Pulmonary Embolism
Upper Extremity
Thrombosis
Demography
Safety
Therapeutics
Population

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Rivaroxaban for thromboprophylaxis in high-risk ambulatory patients with cancer. / CASSINI Investigators.

In: New England Journal of Medicine, Vol. 380, No. 8, 01.01.2019, p. 720-728.

Research output: Contribution to journalArticle

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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.",
author = "{CASSINI Investigators} and Khorana, {Alok A.} and Soff, {Gerald A.} and Kakkar, {Ajay K.} and Saroj Vadhan-Raj and Hanno Riess and Ted Wun and Streiff, {Michael B.} and Garcia, {David A.} and Liebman, {Howard A.} and Belani, {Chandra P.} and O'Reilly, {Eileen M.} and Patel, {Jai N.} and Yimer, {Habte A.} and Peter Wildgoose and Paul Burton and Ujjwala Vijapurkar and Simrati Kaul and John Eikelboom and McBane, {Robert D} and Bauer, {Kenneth A.} and Kuderer, {Nicole M.} and Lyman, {Gary H.}",
year = "2019",
month = "1",
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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 D

AU - Bauer, Kenneth A.

AU - Kuderer, Nicole M.

AU - Lyman, Gary H.

PY - 2019/1/1

Y1 - 2019/1/1

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

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