Antithrombotic therapy for venous thromboembolism in patients with cancer: expert guidance

ABSTRACT

Introduction: Most of the current clinical guidelines recommend the use of Low-Molecular-Weight Heparins (LMWHs) for cancer-associated thrombosis (CAT). The Hokusai VTE-cancer trial reported the first results of a direct comparison between a direct oral anticoagulant (DOAC), edoxaban, and LMWH in this setting.

Areas covered: This review aims to critically appraise the currently available evidence on the efficacy and safety of anticoagulant agents for the long-term treatment of CAT and to provide an expert opinion and guidance in this field.

Expert opinion: Based on the available evidence, DOACs represent a valid alternative to LMWH for the treatment of CAT for the majority of patients with active cancer. Currently, most solid evidence comes from the Hokusai VTE-cancer study, which showed that edoxaban is non-inferior to the LMWH dalteparin, with a trend toward fewer recurrent venous thromboembolic events, but with more major bleeding events. Similar findings were reported with rivaroxaban, although the study was not sufficiently powered to allow definitive conclusions. The majority of bleeding events occurred in the upper gastrointestinal tract and in patients with gastrointestinal cancer. Thus, LMWH remains the preferred option for patients with gastrointestinal cancer. Additional studies aimed to confirm these findings with other DOACs are now warranted.

KEYWORDS:

• (MeSH): low-molecular-weight heparin
• anticoagulants
• edoxaban
• evidence-based practice
• venous thromboembolism

Article highlights

• Cancer-associated thrombosis (CAT) represents a major clinical problem, being the second leading cause of death after the malignancy itself.

• Current clinical guidelines in oncology recommend the use of therapeutic doses of Low-Molecular-Weight Heparins (LMWHs) for the initial and long-term treatment of CAT, but several limitations on the evidence supporting the use of LMWHs as the only agent for treating these patients, as well as practical issues with regard to the long-term therapy with LMWHs, have been reported.

• The Hokusai VTE-cancer trial reported the first results of a direct comparison between a direct oral anticoagulant (DOAC), edoxaban, and LMWH in this setting and showed that edoxaban is non-inferior to the LMWH dalteparin, with a trend toward fewer recurrent venous thromboembolic events and more bleeding events.

• Similar findings were reported with rivaroxaban, although the study was not sufficiently powered to allow definitive conclusions. The majority of bleeding events occurred in the upper gastrointestinal tract and in patients with gastrointestinal cancer.

• The use of the DOACs can be considered in a large proportion of patients with cancer as an alternative to LMWH for the treatment of CAT. Evidence originated from the currently available clinical trials should drive therapeutic decisions in terms of patient selection and dosing regimens.

This box summarizes key points contained in the article.

Acknowledgments

Daiichi Sankyo had no role in the process of design, data interpretation, preparation, and submission of the manuscript for publication.

Declaration of Interest

D Imberti has received consultancy fees from Aspen, Bayer Healthcare, Sanofi, Bristol-Myers Squibb, Pfizer Inc., Daiichi Sankyo, and Boehringer Ingelheim. H Polo Friz has received feeds for collaborations as a medical writer, lecturer, and as part of congresses from Bayer Healthcare, Daiichi Sankyo, Boehringer Ingelheim, Pfizer Inc., Sanofi, Maccann Medical Complete Srl, Health and Life, IMS Health, Clinical Forum Srl, and Medi K Srl. C Cimminiello has received consultancy fees from Bayer Healthcare, Sanofi, Pfizer Inc., Bristol-Myers Squibb, Daiichi Sankyo, Boehringer Ingelheim, Merck Sharp and Dohme, and AstraZeneca. M Di Nisio has received consultancy fees from Bayer Healthcare, Pfizer Inc., Daiichi Sankyo, and Aspen. M Marietta has received personal fees for their participation on advisory boards, collaborations as a consultant and lecture fees from Novo Nordisk, Kedrion, Orphan Europe, and Daiichi Sankyo. Finally, W Ageno has received speaker’s honoraria from Boehringer Ingelheim, Bayer, Bristol-Myers Squibb/Pfizer, Daiichi Sankyo, Aspen, Stago, Sanofi and has participated on scientific advisory boards for Boehringer Ingelheim, Bayer Healthcare, Bristol-Myers Squibb, Pfizer Inc., Daiichi Sankyo, Aspen, Stago, CSL Behring, Sanofi, and Portola and has received research support from Bayer Healthcare. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers of this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This article was developed independently by the authors following an advisory board meeting sponsored by Daiichi Sankyo SpA.