A consensus viewpoint on the role of direct factor Xa inhibitors in the management of cancer-associated venous thromboembolism in the UK

Abstract

Objective

Cancer patients are at high risk of venous thromboembolism (VTE), a significant cause of cancer-related death. Historically, low molecular weight heparins (LMWH) were the gold standard therapy for cancer-associated VTE, but recent evidence supports the use of direct factor Xa inhibitors in cancer-associated VTE and this is now reflected in many guidelines. However, uptake of direct factor Xa inhibitors varies and guidance on the use of direct factor Xa inhibitors in specific cancer sub-populations and clinical situations is lacking. This review presents consensus expert opinion alongside evaluation of evidence to support healthcare professionals in the use of direct factor Xa inhibitors in cancer-associated VTE.

Methods

Recent guidelines, meta-analyses, reviews and clinical studies on anticoagulation therapy for cancer-associated VTE were used to direct clinically relevant topics and evidence to be systematically discussed using nominal group technique. The consensus manuscript and recommendations were developed based on these discussions.

Results

Considerations when prescribing anticoagulant therapy for cancer-associated VTE include cancer site and stage, systemic anti-cancer therapy (including vascular access), drug-drug interactions, length of anticoagulation, quality of life and needs during palliative care. Treatment of patients with kidney or liver impairment, gastrointestinal disorders, extremes of bodyweight, elevated bleeding or recurrence risk, VTE recurrence and COVID-19 is discussed.

Conclusion

Anticoagulant therapy for cancer-associated VTE patients should be carefully selected with consideration given to the relative benefits of specific drugs when individualizing care. Direct factor Xa inhibitors are typically the treatment of choice for preventing VTE recurrence in non-cancer patients and should also be considered as such for cancer-associated VTE in most situations.

Keywords:

• Anticoagulation
• cancer-associated thrombosis
• consensus
• direct oral anticoagulant
• venous thromboembolism

Transparency

Declaration of funding

This work was supported by Pfizer and Bristol Myers Squibb, who financed the medical writing and publication costs during the development and publication of this manuscript. Bristol Myers Squibb actively participated in the development of this manuscript.

Declaration of financial/other relationships

ATC has received fees for serving on an adjudication committee from Boehringer Ingelheim and AbbVie; grant support and fees for serving on committees from Bristol Myers Squibb, Daiichi Sankyo and Pfizer; consulting fees from Janssen, Portola Pharmaceuticals and Ono Pharmaceuticals; fees for serving on a steering committee and consulting fees from Bayer. CAB has received consultant fees/honoraria from Ablynx, Bayer, BMS/Pfizer Alliance, Lilly, Novartis, and Portola Pharmaceuticals; in addition to fees from Amgen, Bayer, BMS/Pfizer Alliance, Eli Lilly, Janssen, and Novartis. AY has received consultant fees/honoraria from BMS/Pfizer Alliance, Chugai and LEO Pharma and an unrestricted educational grant from Bayer. AM has received financial support from Bayer, Boehringer Ingelheim, BMS and LEO Pharma, in addition to consultant fees/honoraria from Bayer, BMS, LEO Pharma and Pfizer. He has also received speaker fees from Bayer, LEO Pharma, Pfizer and Sanofi, and served on advisory boards for Bayer, BMS, LEO Pharma and Pfizer. BV has received consulting fees from Eisai, EUSA Pharma and Ipsen, speaker fees for BMS, Eisai, EUSA Pharma, Ipsen, Merck Sharp & Dohme Oncology, Pfizer/EMD Serono, travel support from BMS, EUSA Pharma and Ipsen, and participation on Data Safety Monitoring boards and//or advisory boards for Merch Sharp & Dohme Oncology, Esai, Janssen. NHJ has received speaker fees from Bayer, BMS, Pfizer, Daiichi Sankyo and Leo Pharma. GB has received speakers and served on advisory boards for BMS, Bayer and Daiichi Sankyo. SC has served on advisory boards with Pfizer, BMS, Jazz and Sanofi. KGP, DB, CC and SM are employees of BMS. ARM and PDG are/were employees of Health Economics and Outcomes Research Ltd., Cardiff, UK. Health Economics and Outcomes Research Ltd. received fees from BMS in relation to this study. RA has received financial support and consultant fees/honoraria from BMS, Bayer, Daiichi Sankyo, Pfizer and Portola Pharmaceuticals.

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

Author contributions

All authors contributed to the conception, writing and review of this article. All authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Acknowledgements

Medical writing and editorial support was provided by Chloe Salter and Jo Whelan of Health Economics and Outcomes Research Ltd., Cardiff, UK. Health Economics and Outcomes Research Ltd. received fees from BMS in relation to this study.

Data availability  statement

None