CC BY 4.0 · TH Open 2019; 03(03): e309-e315
DOI: 10.1055/s-0039-1696659
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Treatment of Cancer-Associated Thrombosis: Beyond HOKUSAI

Isabelle Mahé
1   Université de Paris, Innovations Thérapeutiques en Hémostase, INSERM, Paris, France
2   Service de médecine Interne, AH-HP, Hôpital Louis Mourier, Colombes, Université de Paris, France
3   F-CRIN INNOVTE, Saint Etienne, France
,
Ismaïl Elalamy
3   F-CRIN INNOVTE, Saint Etienne, France
4   Hematology and Thrombosis Center, Tenon University Hospital, Sorbonne University, INSERM U938, Paris, France
5   Department of Obstetrics and Gynecology, The First I.M. Sechenov Moscow State Medical University, Moscow, Russia
,
Grigoris T. Gerotziafas
6   Research Group “Cancer, Haemostasis and Angiogenesis,” INSERM UMR_S 938, Centre de Recherche Saint-Antoine, Faculty of Medicine, Institut Universitaire de Cancérologie, Sorbonne Universities, Paris, France
7   Service d’Hématologie Biologique Hôpital Tenon, Hôpitaux Universitaires de l’Est Parisien, APHP.6, Paris, France
,
Philippe Girard
3   F-CRIN INNOVTE, Saint Etienne, France
8   Institut du Thorax Curie-Montsouris, l’Institut Mutualiste Montsouris, Paris, France
› Author Affiliations
Further Information

Publication History

27 February 2019

25 July 2019

Publication Date:
16 September 2019 (online)

Abstract

Direct oral anticoagulants (DOACs) represent an attractive alternative to low-molecular-weight heparins (LMWHs) for the long-term treatment of cancer-associated thrombosis (CT) since they avoid the burden of daily injections. Analyses in subgroups of cancer patients from large randomized trials suggested that DOACs were at least as effective as vitamin K antagonists, while indirect comparisons suggested that DOACs' efficacy and safety profile were comparable to those of LMWHs. In the randomized controlled HOKUSAI-VTE Cancer study, currently the only completed phase III trial on DOACs in CT patients, edoxaban was shown noninferior to dalteparin on the composite primary endpoint of time to first recurrent venous thromboembolism or major bleeding during the 12 months after randomization. Study results suggest that both agents had comparable benefit/risk ratio in patients with CT. Even though this conclusion was valid from a strict statistical viewpoint, it was potentially misleading when interpreting benefit/risk ratios. Besides the obvious heterogeneity of the study population (e.g., 23% of patients no longer had cancer) and significantly different treatment durations between arms, secondary outcomes for efficacy were in favor of edoxaban for recurrent deep-vein thrombosis but not for recurrent pulmonary embolism, and major bleeding episodes were significantly more frequent in the edoxaban group, with an excess of gastrointestinal (GI) bleeding episodes observed mainly but not only in patients with GI cancers. More research is needed regarding specific patients' profiles, cancer types, and treatment period to better clarify the respective roles of DOACs and LMWHs in CT patients.

 
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