Benjamin Planquette1, Laurent Bertoletti2, Anaïs Charles-Nelson3, Silvy Laporte4, Claire Grange5, Isabelle Mahé6, Gilles Pernod7, Antoine Elias8, Francis Couturaud9, Nicolas Falvo10, Marie Antoinette Sevestre11, Valérie Ray12, Alexis Burnod13, Nicolas Brebion14, Pierre-Marie Roy15, Miruna Timar-David16, Sandro Aquilanti17, Joel Constans18, Alessandra Bura-Rivière19, Dominique Brisot20, Gilles Chatellier3, Olivier Sanchez1, Guy Meyer1, Philippe Girard21, Patrick Mismetti22. 1. Service de Pneumologie et Soins Intensifs, Hôpital Européen Georges Pompidou, APHP, Université de Paris, Paris, France; INSERM UMR_S1140, Innovations Thérapeutiques en Hémostase, Laboratoire de Chirurgie expérimentale, Fondation Alain Carpentier, Paris, France; F-CRIN INNOVTE Network, Saint-Etienne, France. 2. F-CRIN INNOVTE Network, Saint-Etienne, France; Service de Médecine Vasculaire et Thérapeutique, CHU Saint-Etienne, Hôpital Nord, Saint-Etienne, France; INSERM, CIC-1408, CHU Saint-Etienne, Hôpital Nord, Saint-Etienne, France; SAINBIOSE U1059, Université Jean Monnet, INSERM, Saint-Etienne, France. 3. Unité de Recherche Clinique, CIC-EC1418, Hôpital Européen Georges-Pompidou, Paris, France. 4. F-CRIN INNOVTE Network, Saint-Etienne, France; Unité de Recherche Clinique, Innovation, Pharmacologie, CHU Saint-Etienne, Hôpital Nord, Saint-Etienne, France; SAINBIOSE U1059, Université Jean Monnet, INSERM, Saint-Etienne, France. 5. F-CRIN INNOVTE Network, Saint-Etienne, France; Service de Médecine Interne, CHU de Lyon, Pierre Bénite, France. 6. INSERM UMR_S1140, Innovations Thérapeutiques en Hémostase, Laboratoire de Chirurgie expérimentale, Fondation Alain Carpentier, Paris, France; F-CRIN INNOVTE Network, Saint-Etienne, France; Université de Paris, APHP, Hôpital Louis Mourier, Colombes, France. 7. F-CRIN INNOVTE Network, Saint-Etienne, France; Service de Médecine Vasculaire, Université Grenoble-Alpes, Grenoble, France. 8. F-CRIN INNOVTE Network, Saint-Etienne, France; Médecine Vasculaire, Pôle Cardiologie-Vasculaire, Hôpital Sainte Musse, CH de Toulon La Seyne sur Mer, Toulon, France. 9. F-CRIN INNOVTE Network, Saint-Etienne, France; Département de Médecine Interne et Pneumologie, CHU de Brest, Université de Bretagne Occidentale, and EA 3878, CIC INSERM 1412, Brest, France. 10. F-CRIN INNOVTE Network, Saint-Etienne, France; Service de Médecine Interne, CHU de Dijon, Dijon, France. 11. F-CRIN INNOVTE Network, Saint-Etienne, France; Service de Médecine Vasculaire, CHU d'Amiens, Amiens, France. 12. F-CRIN INNOVTE Network, Saint-Etienne, France; Service de Médecine Polyvalente, CHU de Nîmes, Nîmes, France. 13. Département de Soins de Support, Institut Curie, PSL Research University, Paris, France; F-CRIN INNOVTE Network, Saint-Etienne, France. 14. F-CRIN INNOVTE Network, Saint-Etienne, France; Service de Médecine Vasculaire, CHD de Vendée, La Roche sur Yon, France. 15. F-CRIN INNOVTE Network, Saint-Etienne, France; Département des Urgences, CHU d'Angers, et Institut Mitovasc UMR (CNRS 6015-INSERM 1083), Université d'Angers, Angers, France. 16. Service d'Oncologie Médicale, CHU de Nîmes, Nîmes, France. 17. F-CRIN INNOVTE Network, Saint-Etienne, France; Hôpital Privé Arras les Bonnettes, Arras, France. 18. F-CRIN INNOVTE Network, Saint-Etienne, France; Service de Médecine Interne et Vasculaire, CHU de Bordeaux, Bordeaux, France. 19. F-CRIN INNOVTE Network, Saint-Etienne, France; Service de Médecine Vasculaire, CHU de Toulouse, Toulouse, France; Stromalab, UMR 5273 CNRS/UPS-EFS-INSERM U1031, Toulouse, France. 20. F-CRIN INNOVTE Network, Saint-Etienne, France; Service de Médecine Interne et Vasculaire, CHU de Montpellier, Montpellier, France. 21. Département de Pneumologie, Institut Mutualiste Montsouris, Paris, France; F-CRIN INNOVTE Network, Saint-Etienne, France. Electronic address: philippe.girard@imm.fr. 22. F-CRIN INNOVTE Network, Saint-Etienne, France; Service de Médecine Vasculaire et Thérapeutique, CHU Saint-Etienne, Hôpital Nord, Saint-Etienne, France.
Abstract
BACKGROUND: Direct oral anticoagulants (DOACs) are an alternative to low-molecular-weight heparin for treating cancer-associated VTE. RESEARCH QUESTION: Is rivaroxaban as efficient and safe as dalteparin to treat patients with cancer-associated VTE? STUDY DESIGN AND METHODS: In a randomized open-label noninferiority trial, patients with active cancer who had proximal DVT, pulmonary embolism (PE), or both were assigned randomly to therapeutic doses of rivaroxaban or dalteparin for 3 months. The primary outcome was the cumulative incidence of recurrent VTE, a composite of symptomatic or incidental DVT or PE, and worsening of pulmonary vascular or venous obstruction at 3 months. RESULTS: Of 158 randomized patients, 74 and 84 patients were assigned to receive rivaroxaban and dalteparin, respectively. Mean age was 69.4 years, and 115 patients (76.2%) had metastatic disease. The primary outcome occurred in 4 and 6 patients in the rivaroxaban and dalteparin groups, respectively (both the intention-to-treat and per-protocol populations: cumulative incidence, 6.4% vs 10.1%; subdistribution hazard ratio [SHR], 0.75; 95% CI, 0.21-2.66). Major bleeding occurred in 1 and 3 patients in the rivaroxaban and dalteparin groups, respectively (cumulative incidence, 1.4% vs 3.7%; SHR, 0.36; 95% CI, 0.04-3.43). Major or clinically relevant nonmajor bleeding occurred in 9 and 8 patients in the rivaroxaban and dalteparin groups, respectively (cumulative incidence, 12.2% vs 9.8%; SHR, 1.27; 95% CI, 0.49-3.26). Overall, 19 patients (25.7%) and 20 patients (23.8%) died in the rivaroxaban and dalteparin groups, respectively (hazard ratio, 1.05; 95% CI, 0.56-1.97). INTERPRETATION: In this trial comparing rivaroxaban and dalteparin in the treatment of cancer-associated VTE, the number of patients was insufficient to reach the predefined criteria for noninferiority, but efficacy and safety results were consistent with those previously reported with DOACs. An updated meta-analysis of randomized trials comparing DOACs with low-molecular-weight heparin in patients with cancer-associated VTE is provided. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02746185; URL: www. CLINICALTRIALS: gov.
BACKGROUND: Direct oral anticoagulants (DOACs) are an alternative to low-molecular-weight heparin for treating cancer-associated VTE. RESEARCH QUESTION: Is rivaroxaban as efficient and safe as dalteparin to treat patients with cancer-associated VTE? STUDY DESIGN AND METHODS: In a randomized open-label noninferiority trial, patients with active cancer who had proximal DVT, pulmonary embolism (PE), or both were assigned randomly to therapeutic doses of rivaroxaban or dalteparin for 3 months. The primary outcome was the cumulative incidence of recurrent VTE, a composite of symptomatic or incidental DVT or PE, and worsening of pulmonary vascular or venous obstruction at 3 months. RESULTS: Of 158 randomized patients, 74 and 84 patients were assigned to receive rivaroxaban and dalteparin, respectively. Mean age was 69.4 years, and 115 patients (76.2%) had metastatic disease. The primary outcome occurred in 4 and 6 patients in the rivaroxaban and dalteparin groups, respectively (both the intention-to-treat and per-protocol populations: cumulative incidence, 6.4% vs 10.1%; subdistribution hazard ratio [SHR], 0.75; 95% CI, 0.21-2.66). Major bleeding occurred in 1 and 3 patients in the rivaroxaban and dalteparin groups, respectively (cumulative incidence, 1.4% vs 3.7%; SHR, 0.36; 95% CI, 0.04-3.43). Major or clinically relevant nonmajor bleeding occurred in 9 and 8 patients in the rivaroxaban and dalteparin groups, respectively (cumulative incidence, 12.2% vs 9.8%; SHR, 1.27; 95% CI, 0.49-3.26). Overall, 19 patients (25.7%) and 20 patients (23.8%) died in the rivaroxaban and dalteparin groups, respectively (hazard ratio, 1.05; 95% CI, 0.56-1.97). INTERPRETATION: In this trial comparing rivaroxaban and dalteparin in the treatment of cancer-associated VTE, the number of patients was insufficient to reach the predefined criteria for noninferiority, but efficacy and safety results were consistent with those previously reported with DOACs. An updated meta-analysis of randomized trials comparing DOACs with low-molecular-weight heparin in patients with cancer-associated VTE is provided. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02746185; URL: www. CLINICALTRIALS: gov.
Authors: Dominique Farge; Corinne Frere; Jean M Connors; Alok A Khorana; Ajay Kakkar; Cihan Ay; Andres Muñoz; Benjamin Brenner; Pedro H Prata; Dialina Brilhante; Darko Antic; Patricia Casais; María Cecilia Guillermo Esposito; Takayuki Ikezoe; Syed A Abutalib; Luis A Meillon-García; Henri Bounameaux; Ingrid Pabinger; James Douketis Journal: Lancet Oncol Date: 2022-07 Impact factor: 54.433
Authors: Mario Enrico Canonico; Ciro Santoro; Marisa Avvedimento; Giuseppe Giugliano; Giulia Elena Mandoli; Maria Prastaro; Anna Franzone; Raffaele Piccolo; Federica Ilardi; Matteo Cameli; Giovanni Esposito Journal: Biomolecules Date: 2022-02-04
Authors: Marc Carrier; Normand Blais; Mark Crowther; Petr Kavan; Grégoire Le Gal; Otto Moodley; Sudeep Shivakumar; Deepa Suryanarayan; Vicky Tagalakis; Cynthia Wu; Agnes Y Y Lee Journal: Curr Oncol Date: 2021-12-18 Impact factor: 3.677