Treatment of Cancer-Associated Thrombosis: Recent Advances, Unmet Needs, and Future Direction

Cancer-associated thrombosis, with the incidence rising over the years, is associated with significant morbidity and mortality in patients with cancer. Recent advances in the treatment of cancer-associated venous thromboembolism (VTE) include the introduction of direct oral anticoagulants (DOACs), which provide a more convenient and effective option than low-molecular-weight heparin (LMWH). Nonetheless, important unmet needs remain including an increased risk of bleeding in certain patient subgroups such as those with gastroesophageal cancer, concerns about drug-drug interactions, and management of patients with severe renal impairment. Although DOACs are more convenient than LMWH, persistence can decline over time. Factor XI inhibitors have potential safety advantages over DOACs because factor XI appears to be essential for thrombosis but not hemostasis. In phase II trials, some factor XI inhibitors were superior to enoxaparin for the prevention of VTE after knee replacement surgery without increasing the risk of bleeding. Ongoing trials are assessing the efficacy and safety of factor XI inhibitors for the treatment of cancer-associated VTE.

[1]  Tzu‐Fei Wang Drug-drug interactions: Implications for anticoagulation, with focus in patients with cancer. , 2022, Thrombosis research.

[2]  A. Maraveyas,et al.  Practical Treatment Guidance for Cancer-Associated Thrombosis - Managing the Challenging Patient: A Consensus Statement. , 2022, Critical reviews in oncology/hematology.

[3]  G. Raskob,et al.  Milvexian for the Prevention of Venous Thromboembolism. , 2021, The New England journal of medicine.

[4]  D. Gailani,et al.  A proposal for managing bleeding in patients on therapeutic factor XI(a) inhibitors , 2021, Journal of thrombosis and haemostasis : JTH.

[5]  C. Cullen,et al.  Pharmacokinetics and pharmacodynamics of Abelacimab (MAA868), a novel dual inhibitor of Factor XI and Factor XIa , 2021, Journal of thrombosis and haemostasis : JTH.

[6]  G. Chatellier,et al.  Rivaroxaban versus Dalteparin in Cancer-Associated Thromboembolism: A Randomized Trial. , 2021, Chest.

[7]  A. Schmaier,et al.  Polyphosphate expression by cancer cell extracellular vesicles mediates binding of factor XII and contact activation , 2021, Blood advances.

[8]  E. Vicaut,et al.  Extended Anticoagulant Treatment with Full- or Reduced-Dose Apixaban in Patients with Cancer-Associated Venous Thromboembolism: Rationale and Design of the API-CAT Study , 2021, Thrombosis and Haemostasis.

[9]  J. Weitz,et al.  Factor XI Inhibition to Uncouple Thrombosis From Hemostasis: JACC Review Topic of the Week. , 2021, Journal of the American College of Cardiology.

[10]  J. Zwicker,et al.  Characteristics and outcomes of patients on concurrent direct oral anticoagulants and targeted anticancer therapies—TacDOAC registry: Communication from the ISTH SSC Subcommittee on Hemostasis and Malignancy , 2021, Journal of thrombosis and haemostasis : JTH.

[11]  G. Raskob,et al.  Abelacimab for Prevention of Venous Thromboembolism. , 2021, The New England journal of medicine.

[12]  J. Weitz,et al.  Factor XI as a Target for New Anticoagulants , 2021, Hämostaseologie.

[13]  Lara A. Kahale,et al.  American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer. , 2021, Blood advances.

[14]  E. Horváth-Puhó,et al.  Venous thromboembolism in cancer patients: a population-based cohort study. , 2020, Blood.

[15]  L. Bertoletti,et al.  Direct Oral Anticoagulants for the Treatment of Acute Venous Thromboembolism Associated with Cancer: A Systematic Review and Meta-Analysis , 2020, Thrombosis and Haemostasis.

[16]  C. Zielinski,et al.  Direct oral anticoagulants compared to low‐molecular‐weight heparin for the treatment of cancer‐associated thrombosis: Updated systematic review and meta‐analysis of randomized controlled trials , 2020, Research and practice in thrombosis and haemostasis.

[17]  A. Torbicki,et al.  Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer. , 2020, The New England journal of medicine.

[18]  G. Raskob,et al.  Effect of Osocimab in Preventing Venous Thromboembolism Among Patients Undergoing Knee Arthroplasty: The FOXTROT Randomized Clinical Trial. , 2020, JAMA.

[19]  S. Noble,et al.  Patient Experience of Living With Cancer‐Associated Thrombosis in Canada (PELICANADA) , 2019, Research and practice in thrombosis and haemostasis.

[20]  C. Flowers,et al.  Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update. , 2020, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  C. Loprinzi,et al.  Apixaban and dalteparin in active malignancy‐associated venous thromboembolism: The ADAM VTE trial , 2020, Journal of thrombosis and haemostasis : JTH.

[22]  Daniel F. Freitag,et al.  Leveraging Human Genetics to Estimate Clinical Risk Reductions Achievable by Inhibiting Factor XI , 2019, Stroke.

[23]  S. Kakkos,et al.  Editor's Choice - A Systematic Review and Meta-Analysis of the Efficacy and Safety of Anticoagulation in the Treatment of Venous Thromboembolism in Patients with Cancer. , 2019, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[24]  M. Carrier,et al.  How I treat cancer-associated venous thromboembolism. , 2019, Blood.

[25]  G. Raskob,et al.  Clinical Impact of Bleeding in Cancer-Associated Venous Thromboembolism: Results from the Hokusai VTE Cancer Study , 2018, Thrombosis and Haemostasis.

[26]  G. Lyman,et al.  Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism: Results of a Randomized Trial (SELECT-D). , 2018, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  S. Noble,et al.  Patients’ Experience of Living with Cancer-associated thrombosis in Spain (PELICANOS) , 2018, Supportive Care in Cancer.

[28]  G. Raskob,et al.  Edoxaban for the Treatment of Cancer‐Associated Venous Thromboembolism , 2017, The New England journal of medicine.

[29]  S. Dewilde,et al.  What Impact Does Venous Thromboembolism and Bleeding Have on Cancer Patients' Quality of Life? , 2017, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[30]  A. Khorana,et al.  Current practice patterns and patient persistence with anticoagulant treatments for cancer‐associated thrombosis , 2017, Research and practice in thrombosis and haemostasis.

[31]  G. Rennert,et al.  Factor XI deficiency is associated with lower risk for cardiovascular and venous thromboembolism events. , 2017, Blood.

[32]  A. Cohen,et al.  Cancer-associated venous thromboembolism: Burden, mechanisms, and management , 2016, Thrombosis and Haemostasis.

[33]  C. Martinez,et al.  Epidemiology of first and recurrent venous thromboembolism in patients with active cancer , 2016, Thrombosis and Haemostasis.

[34]  Elie A Akl,et al.  Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. , 2012, Chest.

[35]  Catch Investigators Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer: A randomized clinical trial , 2015 .

[36]  S. Noble,et al.  Patients’ Experiences of LIving with CANcer-associated thrombosis: the PELICAN study , 2015, Patient preference and adherence.

[37]  G. Raskob,et al.  Factor XI antisense oligonucleotide for prevention of venous thrombosis. , 2014, The New England journal of medicine.

[38]  A. Khorana,et al.  Efficacy and safety of anticoagulant therapy for the treatment of acute cancer-associated thrombosis: a systematic review and meta-analysis. , 2014, Thrombosis research.

[39]  H. Büller,et al.  Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials. , 2014, Blood.

[40]  J. Connors,et al.  New oral anticoagulants and the cancer patient. , 2014, The oncologist.

[41]  S. Braekkan,et al.  Epidemiology of cancer-associated venous thrombosis. , 2013, Blood.

[42]  A. Carsin,et al.  Associations between cancer‐related financial stress and strain and psychological well‐being among individuals living with cancer , 2013, Psycho-oncology.

[43]  D. Steinberg,et al.  Patients with severe factor XI deficiency have a reduced incidence of deep-vein thrombosis , 2010, Thrombosis and Haemostasis.

[44]  D. Tanné,et al.  Reduced incidence of ischemic stroke in patients with severe factor XI deficiency. , 2008, Blood.

[45]  A. Khorana,et al.  Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy , 2007, Journal of thrombosis and haemostasis : JTH.

[46]  M. Prins,et al.  Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. , 2003, The New England journal of medicine.

[47]  Paolo Prandoni,et al.  Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. , 2002, Blood.

[48]  F. Rosendaal,et al.  High levels of coagulation factor XI as a risk factor for venous thrombosis. , 2000, The New England journal of medicine.

[49]  L. Melton,et al.  Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study. , 2000, Archives of internal medicine.