Khorana AA, et al. - Researchers assessed the benefit of thromboprophylaxis in ambulatory patients receiving systemic cancer therapy and at risk for venous thromboembolism. In the 180-day trial period, no remarkably lower incidence of venous thromboembolism or death due to venous thromboembolism was observed in association with treatment with rivaroxaban in high-risk ambulatory patients with cancer. A substantially lower incidence of such events, with a low incidence of major bleeding, resulting from the rivaroxaban treatment was reported during the intervention period.

Methods

• This was a double-blind, randomized trial.
• Participants were 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).
• For up to 180 days, daily rivaroxaban (at a dose of 10 mg) or placebo was administered randomly to patients without deep-vein thrombosis at screening.
• Participants were screened every 8 weeks.
• Up to day 180, primary efficacy end point was assessed, which comprised 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.
• During the intervention period (first receipt of trial agent to last dose plus 2 days), evaluation of the same end point was done in a prespecified supportive analysis involving the same population.
• Major bleeding was assessed as primary safety end point.

Results

• Among 1080 enrollees, thrombosis was present in 49 (4.5%) at screening and these subjects did not undergo randomization.
• A total of 841 patients were randomized.
• In the rivaroxaban group and in the placebo group, the occurrence of primary end point was noted in 25 of 420 patients (6.0%) and 37 of 421 (8.8%) patients in the respective groups (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, in 11 patients (2.6%) in the rivaroxaban group and in 27 (6.4%) in the placebo group, the occurrence of primary end point was reported (hazard ratio, 0.40; 95% CI, 0.20 to 0.80).
• In 405 patients in the rivaroxaban group and 404 in the placebo group, the occurrence of major bleeding was observed in 8 patients (2.0%) and in 4 (1.0%) patients, respectively (hazard ratio, 1.96; 95% CI, 0.59 to 6.49).