LBA48 - Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism in patients with cancer

Date 27 September 2014
Event ESMO 2014
Session Supportive and palliative care
Topics Supportive Measures
Presenter Martin Prins
Citation Annals of Oncology (2014) 25 (5): 1-41. 10.1093/annonc/mdu438
Authors M.H. Prins1, T. Lensing2, P. Prandoni3, A.T. Cohen4, B. Davidson5, F. Misselwitz2, Á. Pap2, M. Trajanovic6, S. Berkowitz6, P. Wells7
  • 1Medical Center, Maastricht University Medical Center, 6211 - Maastricht/NL
  • 2Bayer Healthcare, Bayer HealthCare AG, Wuppertal/DE
  • 3Department Of Cardiothoracic And Vascular Sciences, University Hospital of Padua, Padue/IT
  • 4Department Of Haematological Medicine, King’s College Hospital, London/GB
  • 5University Of Washington School Of Medicine, University of Washington School of Medicine, Seattle/GB
  • 6Bayer Healthcare Pharmaceuticals, Bayer HealthCare Pharmaceuticals, Whippany/US
  • 7Department Of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa/CA




Objective: To compare the efficacy and safety of oral rivaroxaban with that of enoxaparin/vitamin K antagonist (VKA) in patients with cancer among 8282 patients with acute venous thromboembolism (VTE) enrolled in the EINSTEIN programme.

Rationale: Patients with cancer and VTE constitute a medical challenge for physicians because anticoagulant treatment is indicated to prevent recurrent VTE but is associated with a high risk of major bleeding.


EINSTEIN DVT and EINSTEIN PE were randomized, event-driven, non-inferiority, open-label phase III studies. Patients were treated for 3, 6 or 12 months with rivaroxaban (15 mg twice daily for 21 days followed by 20 mg once daily) or enoxaparin/VKA (international normalized ratio 2.0–3.0) and followed for suspected recurrent VTE, bleeding and mortality. Cancer patients were classified as: active cancer at baseline (diagnosis or treatment within 6 months before enrolment or recurrent/metastatic cancer) or diagnosed during the study (n = 655); or a history of cancer (n = 469).


Recurrent VTE occurred with a similar incidence in the rivaroxaban and enoxaparin/VKA groups in patients with active cancer (hazard ratio [HR] 0.67; 95% confidence interval [CI] 0.35–1.30) and patients with a history of cancer (HR 0.98; 95% CI 0.28–3.43). In patients with active cancer, the risk of major bleeding was significantly reduced in the rivaroxaban group (HR 0.42; 95% CI 0.18–0.99), whereas it was similar between treatments in patients with a history of cancer (HR 0.23; 95% CI 0.03–2.06). Mortality occurred with a similar incidence between treatments in patients with active cancer (HR 0.93; 95% CI 0.64–1.35) and patients with a history of cancer (HR 1.12; 95% CI 0.30–4.22).

Rivaroxaban Enoxaparin/VKA HR (95% CI)
Recurrent VTE, n (%)
Active cancer 16/354 (4.5) 20/301 (6.6) 0.67 (0.35–1.30)
History of cancer 5/233 (2.1) 5/236 (2.1) 0.98 (0.28–3.43)
Major bleeding, n (%)
Active cancer 8/353 (2.3) 15/298 (5.0) 0.42 (0.18–0.99)
History of cancer 1/231 (0.4) 4/236 (1.7) 0.23 (0.03–2.06)
Mortality, n (%)
Active cancer 58/354 (16.4) 53/301 (17.6) 0.93 (0.64–1.35)
History of cancer 5/233 (2.1) 4/236 (1.7) 1.12 (0.30–4.22)


Rivaroxaban had similar efficacy to enoxaparin/VKA in patients with VTE and active cancer or a history of cancer, but was associated with a significant reduction in major bleeding in patients with active cancer.


M.H. Prins: is a consultant advisor for Bayer HealthCare Pharmaceuticals, Daiichi Sankyo, Pfizer, Sanofi, Boehringer Ingelheim, GlaxoSmithKline (GSK), LEO, and ThromboGenics; T. Lensing, F. Misselwitz, Á.F. Pap, M. Trajanovic and S.D. Berkowitz: is an employee of Bayer HealthCare Pharmaceuticals; P. Prandoni: has received consultant fees from Bayer Pharma, Daiichi Sankyo, Pfizer, Boehringer-Ingelheim and Sanofi-Aventis; A.T. Cohen: has received consultancy and clinical trial funding from Astellas, AstraZeneca, Bayer, Boehringer-Ingelheim, BMS, Daiichi, GSK, Johnson & Johnson, Mitsubishi Pharma, Pfizer, Portola, Sanofi-aventis, Schering-Plough & Takeda; B.L. Davidson: has received travel support from Bayer Healthcare, and is a steering committee member for Bayer HealthCare and Daiichi Sankyo;P. Wells: has received research support from Bristol-Myers Squibb, Pfizer; has participated on scientific advisory boards for Bayer Schering Pharma, Pfizer & Boehringer Ingelheim; and has received honoraria from Bayer Schering Pharma, Pfizer & Biomerieux.