CC BY 4.0 · TH Open 2020; 04(02): e107-e112
DOI: 10.1055/s-0040-1712143
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Assessing Full Benefit of Rivaroxaban Prophylaxis in High-Risk Ambulatory Patients with Cancer: Thromboembolic Events in the Randomized CASSINI Trial

Alok A. Khorana
1   Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, Ohio, United States
Mairéad G. McNamara
2   Division of Cancer Sciences, Department of Medical Oncology, University of Manchester, The Christie NHS Foundation Trust, Manchester, United Kingdom
Ajay K. Kakkar
3   Thrombosis Research Institute and University College London, London, United Kingdom
Michael B. Streiff
4   Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
Hanno Riess
5   Department of Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
Ujjwala Vijapurkar
6   Clinical Biostatistics, Janssen Research & Development, LLC, Raritan, New Jersey, United States
Simrati Kaul
7   Medical Affairs Internal Medicine, Janssen Scientific Affairs, LLC, Titusville, New Jersey, United States
Peter Wildgoose
7   Medical Affairs Internal Medicine, Janssen Scientific Affairs, LLC, Titusville, New Jersey, United States
Gerald A. Soff
8   Hematology Service, Memorial Sloan Kettering Cancer Center, New York, New York, United States
on behalf of the CASSINI Investigators › Author Affiliations
Funding This study was funded by Janssen and Bayer ( number: NCT02555878).
Further Information

Publication History

03 October 2019

09 April 2020

Publication Date:
23 May 2020 (online)


Introduction In the CASSINI study, rivaroxaban thromboprophylaxis significantly reduced primary venous thromboembolism (VTE) endpoints during the intervention period, but several thromboembolic events designated as secondary efficacy endpoints were not included in the primary analysis. This study was aimed to evaluate the full impact of rivaroxaban thromboprophylaxis on all prespecified thromboembolic endpoints occurring on study.

Methods CASSINI was a double-blind, randomized, placebo-controlled study in adult ambulatory patients with cancer at risk for VTE (Khorana score ≥2). Patients were screened at baseline for deep-vein thrombosis (DVT) and randomized if none was found. The primary efficacy endpoint was a composite of lower extremity proximal DVT, symptomatic upper extremity, or lower extremity distal DVT, any pulmonary embolism, and VTE-related death. This analysis evaluated all prespecified thromboembolic endpoints occurring on study to determine the full benefit of rivaroxaban prophylaxis. All endpoints were independently adjudicated.

Results Total thromboembolic events occurred in fewer patients randomized to rivaroxaban during the full study period (29/420 [6.9%] and 49/421 [11.6%] patients in rivaroxaban and placebo groups, respectively [hazard ratio (HR) = 0.57; 95% confidence interval (CI): 0.36–0.90; p = 0.01]; number needed to treat [NNT] = 21). Similarly, fewer patients randomized to rivaroxaban experienced thromboembolism during the intervention period (13/420 [3.1%] patients) versus placebo (38/421 [9.0%] patients; HR = 0.33; 95% CI: 0.18–0.62; p < 0.001; NNT = 17).

Conclusion Our findings confirm the substantial benefit of rivaroxaban thromboprophylaxis when considering all prespecified thromboembolic events, even after excluding baseline screen-detected DVT. The low NNT, coupled with prior data demonstrating a high number needed to harm, should assist clinicians in determining the risk/benefit of thromboprophylaxis in high-risk patients with cancer.

Authors' Contributions

A.A.K. contributed to the study design and conduct, data interpretation, and wrote the manuscript. M.G.M., A.K.K., M.B.S., H.R., and G.A.S. contributed to the study design and conduct and data interpretation. U.V. contributed to the data analysis and interpretation. S.K. and P.W. contributed to data interpretation. All authors reviewed and approved the final version of the manuscript for submission.