Extending venous thromboembolism secondary prevention with apixaban in cancer patients: The EVE trial.
apixaban
cancer
secondary prevention
venous thromboembolism
Journal
European journal of haematology
ISSN: 1600-0609
Titre abrégé: Eur J Haematol
Pays: England
ID NLM: 8703985
Informations de publication
Date de publication:
Feb 2020
Feb 2020
Historique:
received:
16
07
2019
revised:
01
10
2019
accepted:
04
10
2019
pubmed:
14
10
2019
medline:
3
10
2020
entrez:
14
10
2019
Statut:
ppublish
Résumé
Cancer-associated venous thromboembolism (VTE) carries a high rate of recurrence and death. Guidelines recommend continued anticoagulation therapy as long as active cancer persists. Apixaban 2.5 mg twice daily is the FDA-approved dose for secondary prevention regardless of VTE causation. Whether this apixaban dose is appropriate for secondary VTE prevention in cancer patients is not clear. The rationale and design of this investigator initiated phase III, multicenter, randomized, double-blind, trial assessing apixaban 2.5 mg vs 5 mg twice daily for 12 months for the secondary VTE prevention in cancer patients (n = 370) who have completed 6 months (but no more than 12 months) of anticoagulation is provided (NCT03080883). The primary study objective is to estimate differences in the combined rate of major plus clinically relevant non-major bleeding for apixaban 2.5 mg vs 5 mg twice daily. Secondary efficacy outcome is to assess rates of venous or arterial thromboembolism. Participating centers are chosen from the Academic and Community Cancer Research United (ACCRU) consortium. We anticipate these trial results to provide evidence supporting low-dose apixaban as a safe agent for secondary prevention of cancer-associated VTE for patients who have already completed 6-12 months of anticoagulation.
Sections du résumé
BACKGROUND
BACKGROUND
Cancer-associated venous thromboembolism (VTE) carries a high rate of recurrence and death. Guidelines recommend continued anticoagulation therapy as long as active cancer persists. Apixaban 2.5 mg twice daily is the FDA-approved dose for secondary prevention regardless of VTE causation. Whether this apixaban dose is appropriate for secondary VTE prevention in cancer patients is not clear. The rationale and design of this investigator initiated phase III, multicenter, randomized, double-blind, trial assessing apixaban 2.5 mg vs 5 mg twice daily for 12 months for the secondary VTE prevention in cancer patients (n = 370) who have completed 6 months (but no more than 12 months) of anticoagulation is provided (NCT03080883).
METHODS/DESIGN
METHODS
The primary study objective is to estimate differences in the combined rate of major plus clinically relevant non-major bleeding for apixaban 2.5 mg vs 5 mg twice daily. Secondary efficacy outcome is to assess rates of venous or arterial thromboembolism. Participating centers are chosen from the Academic and Community Cancer Research United (ACCRU) consortium.
CONCLUSION
CONCLUSIONS
We anticipate these trial results to provide evidence supporting low-dose apixaban as a safe agent for secondary prevention of cancer-associated VTE for patients who have already completed 6-12 months of anticoagulation.
Substances chimiques
Anticoagulants
0
Pyrazoles
0
Pyridones
0
apixaban
3Z9Y7UWC1J
Banques de données
ClinicalTrials.gov
['NCT03080883']
Types de publication
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
88-96Subventions
Organisme : Bristol Myer Squibb
Organisme : Pfizer Alliance
Informations de copyright
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Heit JA, Mohr DN, Silverstein MD, Petterson TM, O'Fallon WM, Melton LJ III. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study. Arch Intern Med. 2000;160:761-768.
Hutten BA, Prins MH, Gent M, Ginsberg J, Tijssen JG, Buller HR. Incidence of recurrent thromboembolic and bleeding complications among patients with venous thromboembolism in relation to both malignancy and achieved international normalized ratio: a retrospective analysis. J Clin Oncol. 2000;18:3078-3083.
Hansson PO, Sorbo J, Eriksson H. Recurrent venous thromboembolism after deep vein thrombosis: incidence and risk factors. Arch Intern Med. 2000;160(6):769-774.
Douketis JD, Foster GA, Crowther MA, Prins MH, Ginsberg JS. Clinical risk factors and timing of recurrent venous thromboembolism during the initial 3 months of anticoagulant therapy. Arch Intern Med. 2000;160:3431-3436.
Prandoni P, Lensing AW, Piccioli A, et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood. 2002;100:3484-3488.
Cushman M, Tsai AW, White RH, et al. Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology. Am J Med. 2004;117:19-25.
Descourt R, Le Gal G, Couturaud F, et al. Recurrent venous thromboembolism under anticoagulant therapy: a high risk in adenocarcinoma? Thromb Haemost. 2006;95:912-913.
Heit JA, Lahr BD, Petterson TM, Bailey KR, Ashrani AA, Melton LJ III. Heparin and warfarin anticoagulation intensity as predictors of recurrence after deep vein thrombosis or pulmonary embolism: a population-based cohort study. Blood. 2011;118(18):4992-4999.
Trujillo-Santos J, Ruiz-Gamietea A, Luque JM, et al. Predicting recurrences or major bleeding in women with cancer and venous thromboembolism. Findings from the RIETE Registry. Thromb Res. 2009;123(Suppl2):S10-S15.
Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016;149:315-352.
Palareti G, Legnani C, Lee A, et al. A comparison of the safety and efficacy of oral anticoagulation for the treatment of venous thromboembolic disease in patients with or without malignancy. Thromb Haemost. 2000;84:805-810.
Elting LS, Escalante CP, Cooksley C, et al. Outcomes and cost of deep venous thrombosis among patients with cancer. Arch Intern Med. 2004;164:1653-1661.
Gross CP, Galusha DH, Krumholz HM. The impact of venous thromboembolism on risk of death or hemorrhage in older cancer patients. J Gen Intern Med. 2007;22(3):321-326.
Ruíz-Giménez N, Suárez C, González R, et al. Predictive variables for major bleeding events in patients presenting with documented acute venous thromboembolism. Findings from the RIETE Registry. Thromb Haemost. 2008;100:26-31.
Hull RD, Pineo GF, Brant RF, et al. Long-term low-molecular-weight heparin versus usual care in proximal-vein thrombosis patients with cancer. Am J Med. 2006;119:1062-1072.
Napolitano M, Saccullo G, Malato A, et al. Optimal duration of low molecular weight heparin for the treatment of cancer-related deep vein thrombosis: the Cancer-DACUS Study. J Clin Oncol. 2014;32:3607-3612.
Francis CW, Kessler CM, Goldhaber SZ, et al. Treatment of venous thromboembolism in cancer patients with dalteparin for up to 12 months: the DALTECAN Study. J Thromb Haemost. 2015;13:1028-1035.
Raskob GE, van Es N, Verhamme P, et al. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med. 2018;378(7):615-624.
Di Nisio M, van Es N, Carrier M, et al. Extended treatment with edoxaban in cancer patients with venous thromboembolism: a post-hoc analysis of the Hokusai-VTE Cancer study. J Thromb Haemost. 2019. [Epub ahead of print].
Young A, Dunn J, Chapman O, et al. Anticoagulation therapy in selected cancer patients at risk of recurrence of venous thromboembolism. J Clin Oncol. 2014;32(15_suppl):TPS9661.
Young AM, Marshall A, Thirlwall J, 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). J Clin Oncol. 2018;36:2017-2023.
McBane R, Loprinzi CL, Ashrani A, et al. Apixaban and dalteparin in active malignancy associated venous thromboembolism. The ADAM VTE Trial. Thromb Haemost. 2017;117:1952-1961.
McBane R2nd, Wysokinski WE, Le-Rademacher JG, et al. Apixaban and Dalteparin in active malignancy associated venous thromboembolism: the ADAM VTE trial. J Thromb Haemost. 2019. [Epub ahead of print].
Khorana AA, Noble S, Lee AYY, et al. Role of direct oral anticoagulants in the treatment of cancer-associated venous thromboembolism: guidance from the SSC of the ISTH. J Thromb Haemost. 2018;16:1891-1894.
Key NS, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol. 2019. [Epub ahead of print].
Streiff MB, Holmstrom B, Angelini D, et al. NCCN guidelines insights: cancer-associated venous thromboembolic disease, version 2.2018. J Natl Compr Canc Netw. 2018;16(11):1289-1303.
Agnelli G, Buller HR, Cohen A, et al. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013;368:699-708.
EINSTEIN Investigators, Bauersachs R, Berkowitz SD, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363:2499-2510.
Weitz JI, Lensing AWA, Prins MH, et al. Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med. 2017;376:1211-1222.
Schulman S, Kearon C, Kakkar AK, et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013;368:709-718.
Lee AYY. When can we stop anticoagulation in patients with cancer-associated thrombosis? Hematology Am Soc Hematol Educ Program. 2017;2017(8):128-135.
Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008;111:4902-4907.
Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005;3:692-694.
Kaatz S, Ahmad D, Spyropoulos AC, Schulman S. Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. J Thromb Haemost. 2015;13:2119-2126.
Girard P, Penaloza A, Parent F, et al. Reproducibility of clinical events adjudications in a trial of venous thromboembolism prevention. J Thromb Haemost. 2017;15:662-669.
Chee CE, Ashrani AA, Marks RS, et al. Predictors of venous thromboembolism recurrence and bleeding among active cancer patients: a population-based cohort study. Blood. 2014;123:3972-3978.
Baron TH, Kamath PS, McBane RD. Management of antithrombotic therapy in patients undergoing invasive procedures. N Engl J Med. 2013;368:2113-2124.
Vedovati MC, Germini F, Agnelli G, et al. Direct oral anticoagulants in patients with VTE and cancer: a systematic review and meta-analysis. Chest. 2015;147:475-483.
Bott-Kitslaar DM, McBane RD, Casanegra AI, et al. Apixaban and rivaroxaban in patients with acute venous thromboembolism. Mayo Clin Proc. 2019;94:1242-1252.