Thrombose associée au cancer. Prévention et traitement. Guy Meyer Université Paris Descartes Hopital Europeen Georges Pompidou, Paris, France

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1 Thrombose associée au cancer Prévention et traitement Guy Meyer Université Paris Descartes Hopital Europeen Georges Pompidou, Paris, France

2 Conflits d intérêt G Meyer Investigateur: Bayer, Daichi-Sankyo, Sanofi Aventis, Leo Pharma Subvention de recherche: Leo Pharma, Boehringer-Ingelheim, Bayer Interventions, boards non rémunérés: Sanofi Aventis, Leo Pharma, Bayer, Boehringer- Ingelheim Invitations congrès: Leo Pharma, Boehringer- Ingelheim, Bayer

3 Une pathologie des cancers les plus agressifs Timp J.F. et al. Blood 2013; 122:

4 Une pathologie des cancers métasta5ques Localized disease Metastatic disease Chew et al. Arch Intern Med 2006; 166:

5 Facteurs de risque de MTVE au cours du cancer Type of cancer: pancreas, myeloma, lung, estomac, ovary Histology: adenocarcinoma Delay: the first four months Stage: metastatic Chemotherapy: platin, anthracyclines, IMiDs Hormons Surgery for cancer Radiotherapy Supportive care: Erythropoeitin, transfusions General risk factors: previous VTE, BMI

6 Score de risque pendant la chimiothérapie 115 US Centers ; 3,196 patients chemotherapy < 4 cycles Characteristics Score Site of cancer Very high risk (pancreas, stomach) High risk (lymphoma, lung, gynecological, genito-urinary) Platelet count > 350,000/mm 3 1 Hemoglobin < 10g/dL 1 Leukocyte count > 11,000/mm 3 1 BMI > 35 kg/m Khorana AA et al. Blood 2008;111:

7 Score de risque pendant la chimiothérapie Risk of VTE over 2.5 months (%) (0) (1-2) (> 3) Khorana A.A. et al. Blood 2008;111:

8 Prolonged prophylaxis: PROTECHT Nadroparin 3800 IU (4 months) (n = 799) vs placebo (n = 387) 3.9% vs 2.0%; p = 0.02 Agnelli G. et al. Lancet Oncol 2009; 10:

9 SAVE- ONCO Metastatic or locally advanced cancer with chemotherapy Semuloparin, n = 1608 or placebo n = 1604; HR: 0,36 ; 0,21-0,60; p < 0,001 Agnelli G. et al. N Engl J Med 2012; 366: 601-9

10 High- risk groups (PROTECHT and SAVE- ONCO) Placebo % VTE Placebo Nadroparin Semuloparin Verso M. et al. Intern Emerg Med 2012; 7:

11 VKA in pa5ents with cancer- associated thrombosis Prospective study 842 VTE patients including 181 patients with CAT Heparin + VKA Patients without cancer N = 661 Patients with cancer N =181 Hazard ratio Recurrent VTE (%) 6.8 ( ) 20.7 ( ) 3.2 ( ) Major bleeding (%) 4.9 ( ) 12.4 ( ) 2.2 ( ) Prandoni P. et al. Blood 2002; 100:

12 The CLOT Study Multicenter randomized open trial 672 patients with cancer and venous thromboembolism Dalteparin (n = 336): 200 IU/kg 1 month followed by 150 IU/kg 5 months Warfarin ( n = 336): INR months Major endpoint : objectively confirmed VTE recurrences. Lee A. et al. N Engl J Med 2003; 349:

13 The CLOT Study Lee A. et al. N Engl J Med 2003; 349:

14 The CLOT Study Recurrences* Major bleedings Mortality Dalteparin 8.8% 5.6% 39% Warfarin 17.4% 3.6% 41% *: p = Lee A. et al. N Engl J Med 2003; 349:

15 Recurrences with LMWH and VKA in pa5ents with cancer- associated thrombosis 0.53 ( ) Louzada M. et al. Thromb Res 2009; 123:

16 Bleedings during LMWH and VKA in pa5ents with cancer- associated thrombosis 0.98 ( ) Louzada M. et al. Thromb Res 2009; 123:

17 Therapeu5c dilemna aqer 3 to 6 months of LMWH treatment No published experience with LMWH Sustained benefit vs VKA? Tolerance of LMWH injections Evolution and cancer treatment Prognosis Patient s preferences

18 Recurrent VTE during an5coagulant treatment? Vena cava interruption? Little published experience, do not provide control of hypercoagulability Fondaparinux? Little experience for the long-term treatment in patients with cancer Increase LMWH dosage?

19 Increase LMWH dosage? 70 patients, cancer, recurrent VTE Increase LMWH dosage by 20% (47) Replacement of VKA by LMWH (23) 3 months follow-up 6 new recurrences (9.9%) 3 bleedings (4.3%) Carrier M. et al. J Thromb Haemost. 2009; 7:

20 Clinically unsuspected incidental PE

21 Incidental and symptoma5c PE share the same risk of recurrent VTE Sahut d Izarn M. et al. J Thromb Haemost 2012; 10:

22 Cancer patients in the pivotal trials of DOA in VTE Study Control Experimental Einstein (DVT-PE) RECOVER-I-II Amplify Hokusai Prins M. et al. Thromb Journal 2013; 11: 21 Schulman S. et al. Circulation 2013; Dec 16 Agnelli G. et al. N Engl J Med 2013; 369: Buller H. et al. N Engl J Med 2013; 369:

23 Recurrent VTE: DOA vs VKA Vedovati MC. et al. Chest Sep 11.

24 Major bleeding: DOA vs VKA Vedovati MC. et al. Chest Sep 11.

25 Conclusion LMWH remains the preferred therapeutic option for the treatment of Cancer Associated Thrombosis. LMWH should be given for at least 3 to 6 months. Anticoagulant treatment should be continued after 6 months for the majority of patients with CAT. The optimal treatment option after 6 months of LMWH treatment remains to be defined.