Rivaroxaban for Thromboprophylaxis in High-Risk Ambulatory Patients With Cancer - CASSINI

Feb 27, 2019
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Janssen
Date Published:
02/21/2019
Date Updated:
02/27/2019
Original Posted Date:
02/27/2019
References

Contribution To Literature:

The CASSINI trial failed to show that rivaroxaban was superior to placebo at preventing thromboembolic events.

Description:

The goal of the trial was to evaluate rivaroxaban compared with placebo among high-risk ambulatory patients with cancer.


Study Design

  • Randomized
  • Parallel
  • Placebo
  • Double-blind

High-risk ambulatory patients with cancer were randomized to rivaroxaban 10 mg daily (n = 420) versus placebo (n = 421) for up to 180 days. Patients were screened for venous thromboembolism prior to beginning study medication.

  • Total number of enrollees: 841
  • Duration of follow-up: 180 days
  • Mean patient age: 62 years
  • Percentage female: 51%

Inclusion criteria:

  • Patients ≥18 years of age with cancer (solid tumor or lymphoma)

Exclusion criteria:

  • Venous thromboembolism
  • Primary brain tumor or brain metastases
  • Eastern Cooperative Oncology Group performance-status score of ≥3
  • Active bleeding or risk for bleeding

Other salient features/characteristics:

  • Mean intervention period: 4.3 months
  • In the rivaroxaban group, 43.7% discontinued study medication prematurely vs. 50.2% in the placebo group

Principal Findings:

The primary outcome, 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, or death from venous thromboembolism at 180 days, occurred in 6.0% of the rivaroxaban group compared with 8.8% of the placebo group (p = 0.10). Thirty-nine percent of primary endpoint events occurred after discontinuation of study medication.

Secondary outcomes:

  • Primary outcome during intervention period: 2.6% for rivaroxaban vs. 6.4% for placebo (p < 0.05)
  • Major bleeding: 2.0% for rivaroxaban vs. 1.0% for placebo (p = not significant [NS])
  • Serious adverse events: 43.3% for rivaroxaban vs. 41.5% for placebo (p = NS)

Interpretation:

Among high-risk patients with cancer, rivaroxaban was not superior to placebo at preventing venous thromboembolic events. Bleeding events were low and similar between treatment groups. A large proportion of patients discontinued study medication prematurely, which accounts for the lack of treatment benefit for rivaroxaban.

References:

Khorana AA, Soff GA, Kakkar AK, et al. Rivaroxaban for Thromboprophylaxis in High-Risk Ambulatory Patients With Cancer. N Engl J Med 2019;380:720-8.

Editorial: Agnelli G. Direct Oral Anticoagulants for Thromboprophylaxis in Ambulatory Patients With Cancer. N Engl J Med 2019;380:781-3.

Keywords: Anticoagulants, Cardiotoxicity, Hemorrhage, Lymphoma, Neoplasms, Primary Prevention, Pulmonary Embolism, Vascular Diseases, Venous Thromboembolism, Venous Thrombosis


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