Rivaroxaban bei tumorassoziierter venöser Thromboembolie

Rupert Bauersachs; Minna Voigtländer; Florian Langer

doi:10.1055/a-1933-1391

DMW - Deutsche Medizinische Wochenschrift, Inhaltsverzeichnis

Dtsch Med Wochenschr 2022; 147(23): 1545-1551
DOI: 10.1055/a-1933-1391

Review

Rivaroxaban bei tumorassoziierter venöser Thromboembolie

Rivaroxaban in patients with cancer-associated thromboembolism

Rupert Bauersachs

¹Cardioangiologisches Centrum Bethanien – CCB, Gefäß-Centrum; Frankfurt am Main

,

Minna Voigtländer

²II. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg

,

Florian Langer

¹Cardioangiologisches Centrum Bethanien – CCB, Gefäß-Centrum; Frankfurt am Main

› Institutsangaben

Abstract

Zusammenfassung

Diese Übersichtsarbeit beschreibt Erkenntnisse zur Prävention und Therapie der tumorassoziierten venösen Thromboembolie (VTE) mit direkten Faktor-Xa-Inhibitoren (FXaI) und bezieht sich insbesondere auf das Studienprogramm CALLISTO mit Rivaroxaban. CALLISTO umfasst randomisierte klinische Prüfungen unterschiedlicher Fragestellungen sowie Real-World-Evidenz.

Prävention und Therapie der tumorassoziierten VTE beruhten bisher auf niedermolekul1933aren Heparinen (NMH). Randomisierte kontrollierte Studien zeigten nun eine vergleichbare bis überlegene Wirksamkeit von FXaI vs. NMH. Die Erkenntnisse finden mittlerweile Eingang in Empfehlungen und Leitlinien. Zu beachten ist ein ggf. erhöhtes Blutungsrisiko, vor allem bei Patienten mit nicht resezierten gastrointestinalen oder urogenitalen Tumoren. Dieses wurde bei der Therapie mit FXaI zuerst beobachtet, kann jedoch auch NMH betreffen. Der Selektion geeigneter Patienten und der Optimierung von Behandlungspfaden kommt daher eine hohe Bedeutung zu.

Abstract

This review article describes insights into the prevention and treatment of cancer-associated venous thromboembolism (VTE) with direct factor Xa inhibitors (FXaI) and refers in particular to the CALLISTO study program with rivaroxaban. CALLISTO includes randomized clinical trials on different topics as well as real-world evidence.

Prevention and treatment of cancer-associated VTE have so far relied on low molecular weight heparins (LMWH). Meanwhile, randomized controlled trials have found comparable to superior efficacy of FXaI vs. LMWH, and the findings are now being incorporated into recommendations and guidelines. A possibly increased risk of bleeding, especially in patients with unresected gastrointestinal or urogenital tumors, should be considered. This was first observed during therapy with FXaI but can also affect LMWH. The selection of suitable patients and the optimization of treatment pathways are therefore of great importance.

Schlüsselwörter

Antikoagulation - Krebs - Rivaroxaban - Thrombose - venöse Thromboembolie

Keywords

anticoagulation - cancer - rivaroxaban - thrombosis - venous thromboembolism

Volltext

Referenzen

Literatur
1 Mulder FI, Horváth-Puhó E, van Es N. et al. Venous thromboembolism in cancer patients: a population-based cohort study. Blood 2021; 137: 1959-1969
2 Lyman GH. Venous thromboembolism in the patient with cancer: focus on burden of disease and benefits of thromboprophylaxis. Cancer 2011; 117: 1334-1349
3 Bach M, Bauersachs R. Spotlight on advances in VTE management: CALLISTO and EINSTEIN CHOICE. Thromb Haemost 2016; 116: S24-S32
4 Mahajan A, Brunson A, Adesina O. et al. The incidence of cancer-associated thrombosis is increasing over time. Blood Adv 2022; 6: 307-320
5 Farge D, Frere C, Connors JM. et al. 2019 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. Lancet Oncol 2019; 20: e566-e581
6 Carrier M, Abou-Nassar K, Mallick R. et al. Apixaban to Prevent Venous Thromboembolism in Patients with Cancer. N Engl J Med 2019; 380: 711-719
7 Becattini C, Pace U, Rondelli F. et al. Rivaroxaban for extended antithrombotic prophylaxis after laparoscopic surgery for colorectal cancer. Design of the PRO-LAPS II STUDY. Eur J Intern Med 2020; 72: 53-59
8 Fadoi Foundation, Italy. Rivaroxaban or Placebo for Extended Antithrombotic Prophylaxis After Laparoscopic Surgery for Colorectal Cancer: a Randomized, Double Blind, Placebo-controlled Study. clinicaltrials.gov 2019;
9 Raskob GE, van Es N, Verhamme P. et al. Edoxaban for the Treatment of Cancer-Associated Venous Thromboembolism. N Engl J Med 2018; 378: 615-624
10 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 Off J Am Soc Clin Oncol 2018; 36: 2017-2023
11 McBane RD, Wysokinski WE, Le-Rademacher JG. et al. Apixaban and dalteparin in active malignancy-associated venous thromboembolism: The ADAM VTE trial. J Thromb Haemost JTH 2020; 18: 411-421
12 Cohen AT, Maraveyas A, Beyer-Westendorf J. et al. Patient-reported outcomes associated with changing to rivaroxaban for the treatment of cancer-associated venous thromboembolism – The COSIMO study. Thromb Res 2021; 206: 1-4
13 Agnelli G, Becattini C, Meyer G. et al. Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer. N Engl J Med 2020; 382: 1599-1607
14 Planquette B, Bertoletti L, Charles-Nelson A. et al. Rivaroxaban vs Dalteparin in Cancer-Associated Thromboembolism: A Randomized Trial. Chest 2021; S0012-3692(21)04079-4
15 Riess H, Verhamme P, Weitz JI. et al. Treatment of cancer-associated thrombosis: The evolution of anticoagulant choice and clinical insights into practical management. Crit Rev Oncol Hematol 2021; 157: 103125
16 Mulder FI, Bosch FTM, Young AM. et al. Direct oral anticoagulants for cancer-associated venous thromboembolism: a systematic review and meta-analysis. Blood 2020; 136: 1433-1441
17 Moik F, Posch F, Zielinski C. 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. Res Pract Thromb Haemost 2020; 4: 550-561
18 Khorana AA, Soff GA, Kakkar AK. et al. Rivaroxaban for Thromboprophylaxis in High-Risk Ambulatory Patients with Cancer. N Engl J Med 2019; 380: 720-728
19 Khorana AA, Kuderer NM, Culakova E. et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008; 111: 4902-4907
20 Hart C, Heudobler D, Linnemann B. [Thromboprophylaxis in ambulatory patients with cancer]. Dtsch Med Wochenschr 1946 2020; 145: 130-134
21 Pabinger I, van Es N, Heinze G. et al. A clinical prediction model for cancer-associated venous thromboembolism: a development and validation study in two independent prospective cohorts. Lancet Haematol 2018; 5: e289-e298
22 Kimpton M, Wells PS, Carrier M. Apixaban for the prevention of venous thromboembolism in high-risk ambulatory cancer patients receiving chemotherapy: Rational and design of the AVERT trial. Thromb Res 2018; 164 (Suppl. 01) S124-S129
23 Becattini C, Pace U, Pirozzi F. et al. Rivaroxaban versus placebo for extended antithrombotic prophylaxis after laparoscopic surgery for colorectal cancer. Blood 2022;
24 Marshall A, Levine M, Hill C. et al. Treatment of cancer-associated venous thromboembolism: 12-month outcomes of the placebo versus rivaroxaban randomization of the SELECT-D Trial (SELECT-D: 12m). J Thromb Haemost JTH 2020; 18: 905-915
25 Kraaijpoel N, Di Nisio M, Mulder FI. et al. Clinical Impact of Bleeding in Cancer-Associated Venous Thromboembolism: Results from the Hokusai VTE Cancer Study. Thromb Haemost 2018; 118: 1439-1449
26 Mulder FI, van Es N, Kraaijpoel N. et al. Edoxaban for treatment of venous thromboembolism in patient groups with different types of cancer: Results from the Hokusai VTE Cancer study. Thromb Res 2020; 185: 13-19
27 Konstantinides SV, Meyer G, Becattini C. et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J 2020; 41: 543-603
28 Kearon C, Akl EA, Ornelas J. et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest 2016; 149: 315-352
29 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 JTH 2015; 13: 1028-1035
30 Lee AYY. When can we stop anticoagulation in patients with cancer-associated thrombosis?. Blood 2017; 130: 2484-2490
31 Jara-Palomares L, Solier-Lopez A, Elias-Hernandez T. et al. Tinzaparin in cancer associated thrombosis beyond 6months: TiCAT study. Thromb Res 2017; 157: 90-96
32 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 JTH 2019; 17: 1866-1874
33 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 Off J Am Soc Clin Oncol 2020; 38: 496-520
34 Riess H, Angelillo-Scherrer A, Alt-Epping B. et al Thromboembolien bei Tumorpatienten (früher: Venöse Thromboembolien (VTE) bei Tumorpatienten). Onkopedia. Im Internet (Stand: 21.12.2021): https://www.onkopedia.com/de/onkopedia/guidelines/thromboembolien-bei-tumorpatienten-frueher-venoese-thromboembolien-vte-bei-tumorpatienten
35 Stevens SM, Woller SC, Kreuziger LB. et al. Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report. Chest 2021; 160: e545-e608
36 Konstantinides S, Lankeit M. Kommission für Klinische Kardiovaskuläre Medizin der DGK. et al. Kommentar zu den Leitlinien (2019) der European Society of Cardiology zum Management der akuten Lungenembolie: Unter Mitwirkung der European Respiratory Society (ERS). Kardiologe 2020; 14: 248-255
37 Lyman GH, Carrier M, Ay C. et al. American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer. Blood Adv 2021; 5: 927-974
38 Steffel J, Collins R, Antz M. et al. 2021 European Heart Rhythm Association Practical Guide on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation. Eur Eur Pacing Arrhythm Card Electrophysiol J Work Groups Card Pacing Arrhythm Card Cell Electrophysiol Eur Soc Cardiol 2021; 23: 1612-1676
39 McBane RD, Wysokinski WE, Le-Rademacher J. et al. Apixaban, Dalteparin, in Active Cancer Associated Venous Thromboembolism, the ADAM VTE Trial. Blood 2018; 132: 421
40 Maraveyas A, Beyer-Westendorf J, Lee AYY. et al. Baseline Characteristics and Clinical Outcomes from the Cancer Associated Thrombosis – Patient Reported Outcomes with Rivaroxaban (COSIMO) Trial. Blood 2019; 134: 2161
41 EUPAS12608. COSIMO Cancer associated thrombosis – patient reported outcomes with rivaroxaban. A non-interventional study on patients changing to Xarelto® for treatment of venous thromboembolism (VTE) and prevention of recurrent VTE in patients with active cancer. Im Internet (Stand: 21.12.2021): https://www.encepp.eu/encepp/viewResource.htm?id=33638
42 Picker N, Lee AY, Cohen AT. et al. Anticoagulation Treatment in Cancer-Associated Venous Thromboembolism: Assessment of Patient Preferences Using a Discrete Choice Experiment (COSIMO Study). Thromb Haemost 2021; 121: 206-215
43 Kakkar AK, Bauersachs R, Falanga A. et al. Fundamental Research in Oncology and Thrombosis 2 (FRONTLINE 2): A Follow-Up Survey. The Oncologist 2020; 25: e1091-e1097
44 Kakkar AK, Levine M, Pinedo HM. et al. Venous thrombosis in cancer patients: insights from the FRONTLINE survey. The Oncologist 2003; 8: 381-388
45 Riess H, Kretzschmar A, Heinken A. et al. Anticoagulation Therapy in Cancer Patients with Thrombosis in the Outpatient Sector of Germany (The CERTIFICAT Initiative)—German Practice of Anticoagulation Therapy of Cancer Patients with Thrombosis. Hämostaseologie 2022; 42: 166-173
46 Klamroth R, Sinn M, Pollich C. et al. Anticoagulation Practice in Patients with Cancer-Associated Thrombosis: Insights from GeCAT, a German Prospective Registry Study. Oncol Res Treat 2022; 45: 178-185
47 Mantha S, Laube E, Miao Y. et al. Safe and effective use of rivaroxaban for treatment of cancer-associated venous thromboembolic disease: a prospective cohort study. J Thromb Thrombolysis 2017; 43: 166-171
48 Soff GA, Mones J, Wilkins C. et al. Rivaroxaban treatment of cancer-associated venous thromboembolism: Memorial Sloan Kettering Cancer Center institutional experience. Res Pract Thromb Haemost 2019; 3: 349-356
49 Langer F. Antikoagulation mit NMH und NOAK. Therapie von tumorassoziierten Thromboembolien. Best Pract Onkol Beil Für Onkol 2019; 14: 1-4
50 Ay C, Beyer-Westendorf J, Pabinger I. Treatment of cancer-associated venous thromboembolism in the age of direct oral anticoagulants. Ann Oncol Off J Eur Soc Med Oncol 2019; 30: 897-907
51 Wang T-F, Zwicker JI, Ay C. et al. The use of direct oral anticoagulants for primary thromboprophylaxis in ambulatory cancer patients: Guidance from the SSC of the ISTH. J Thromb Haemost JTH 2019; 17: 1772-1778

Zusatzmaterial