Subscribe to RSS
Assessing Full Benefit of Rivaroxaban Prophylaxis in High-Risk Ambulatory Patients with Cancer: Thromboembolic Events in the Randomized CASSINI TrialFunding This study was funded by Janssen and Bayer (ClinicalTrials.gov number: NCT02555878).
03 October 2019
09 April 2020
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.
Keywordsarterial thrombosis - cancer - thrombolysis/thrombolytic agents - thromboprophylaxis - venous thrombosis
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.
- 1 Connors JM. Prophylaxis against venous thromboembolism in ambulatory patients with cancer. N Engl J Med 2014; 370 (26) 2515-2519
- 2 Navi BB, Reiner AS, Kamel H. , et al. Risk of arterial thromboembolism in patients with cancer. J Am Coll Cardiol 2017; 70 (08) 926-938
- 3 Agnelli G, Gussoni G, Bianchini C. , et al; PROTECHT Investigators. Nadroparin for the prevention of thromboembolic events in ambulatory patients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomised, placebo-controlled, double-blind study. Lancet Oncol 2009; 10 (10) 943-949
- 4 Agnelli G, George DJ, Kakkar AK. , et al; SAVE-ONCO Investigators. Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. N Engl J Med 2012; 366 (07) 601-609
- 5 Khorana AA, Soff GA, Kakkar AK. , et al; CASSINI Investigators. Rivaroxaban for thromboprophylaxis in high-risk ambulatory patients with cancer. N Engl J Med 2019; 380 (08) 720-728
- 6 Carrier M, Abou-Nassar K, Mallick R. , et al; AVERT Investigators. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med 2019; 380 (08) 711-719
- 7 Khorana AA, Vadhan-Raj S, Kuderer NM. , et al. Rivaroxaban for preventing venous thromboembolism in high-risk ambulatory patients with cancer: rationale and design of the CASSINI trial. Thromb Haemost 2017; 117 (11) 2135-2145
- 8 Flanc C, Kakkar VV, Clarke MB. The detection of venous thrombosis of the legs using 125-I-labelled fibrinogen. Br J Surg 1968; 55 (10) 742-747
- 9 Beck-Razi N, Kuzmin A, Koren D. , et al. Asymptomatic deep vein thrombosis in advanced cancer patients: the value of venous sonography. J Clin Ultrasound 2010; 38 (05) 232-237
- 10 Yamashita Y, Shiomi H, Morimoto T. , et al. Asymptomatic lower extremity deep vein thrombosis- clinical characteristics, management strategies, and long-term outcomes. Circ J 2017; 81 (12) 1936-1944
- 11 Menapace LA, Peterson DR, Berry A, Sousou T, Khorana AA. Symptomatic and incidental thromboembolism are both associated with mortality in pancreatic cancer. Thromb Haemost 2011; 106 (02) 371-378
- 12 Gary T, Belaj K, Steidl K. , et al. Asymptomatic deep vein thrombosis and superficial vein thrombosis in ambulatory cancer patients: impact on short-term survival. Br J Cancer 2012; 107 (08) 1244-1248
- 13 Brenner B, Bikdeli B, Tzoran I. , et al; RIETE Investigators. Arterial ischemic events are a major complication in cancer patients with venous thromboembolism. Am J Med 2018; 131 (09) 1095-1103
- 14 Galanaud JP, Sevestre MA, Pernod G. , et al. Long-term outcomes of cancer-related isolated distal deep vein thrombosis: the OPTIMEV study. J Thromb Haemost 2017; 15 (05) 907-916