lyman-350 The February issue of the Journal of Clinical Oncology features the most recent update of the ASCO clinical guidelines on venous thromboembolism (VTE) prophylaxis and treatment in patients with cancer. The goal of this guideline update is to provide oncologists and other clinicians with latest recommendations regarding the prevention and treatment of venous thromboembolism (VTE) in patients with cancer. The key recommendations in this paper are as follows:

  • Most hospitalized patients with active cancer require thromboprophylaxis throughout hospitalization. Data are inadequate to support routine thromboprophylaxis in patients admitted for minor procedures or short chemotherapy infusion.
  • Routine thromboprophylaxis is not recommended for ambulatory patients with cancer.
    It may be considered for highly select, high-risk patients. See Table 1 for predicting
    outpatient VTE risk score for patients with cancer.
  • ASCOPatients with multiple myeloma receiving antiangiogenesis agents with chemotherapy and/or dexamethasone should receive prophylaxis with either low-molecular weight heparin (LMWH) or low-dose aspirin to prevent venous thromboembolism (VTE).
  • Patients undergoing major cancer surgery should receive prophylaxis starting before surgery and continuing for at least 7 to 10 days.
  • Extending postoperative prophylaxis up to 4 weeks should be considered in those undergoing major abdominal or pelvic surgery with high-risk features.
  • LMWH is recommended for the initial 5 to 10 days of treatment of established deep vein thrombosis and pulmonary embolism as well as for long-term secondary prophylaxis for at least 6 months.
  • Use of novel oral anticoagulants (NOACs) is currently not recommended for patients with malignancy and VTE.
  • Anticoagulation should not be used to extend survival of patients with cancer in the absence of other indications.
  • Patients with cancer should be periodically assessed for VTE risk.
  • Oncology professionals should educate patients about the signs and symptoms of VTE.

table1

Reference

Lyman G, Bohlke K, Khorana A, et al. Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update 2014. J Clin Oncol 2015;33(6).


 

figuur-350Figure. Acute thrombotic microangiopathyDue to their high safety and efficacy profile, low molecular weight heparins (LMWHs) are recommended as the treatment of choice for acute and long-term management of cancer-associated thrombosis (CAT). In recent years, however, a generation of direct oral anticoagulants (DOACs) has been introduced and evaluated in clinical trials. These pharmacologic agents were found to be at least as safe and effective as traditional anticoagulant therapies (i.e. LMWHs and vitamin-K antagonists [VKA]) for the treatment of acute venous thromboembolism (VTE) and for secondary VTE prophylaxis. Two types of DOACs are currently available: the factor Xa inhibitors apixaban, edoxaban and rivaroxaban, and the thrombin inhibitor dabigatran. In Thrombosis Research a review listing all published clinical trials evaluating the efficacy and safety of DOACs in patients with cancer was recently published as e-pub ahead of print.

The use of DOACs in patients with cancer is potentially attractive as they have favourable pharmacokinetics, do not require subcutaneous injections - due to oral administration - or anticoagulation monitoring and have few significant drug interactions. Unfortunately, beside a randomized trial with apixaban (Levine et al, J Thromb Haemost 2012), no other studies have specifically addressed the role of DOACs in cancer-associated VTE. Moreover, available data come from subgroup analyses of small number of cancer patients recruited in the large phase III randomized acute VTE trials. These data were analysed separately for each DOAC in this review and are summarized in the Table below.

Based on the results of this analysis and on the outcome of three recently reported meta-analyses including data from the studies listed below (Sardar et al, Am J Ther 2014; van der Hulle et al, J Thromb Haemost 2014; Vedovati et al, Chest 2015) the authors conclude that DOACs have potential for treating and preventing VTE in cancer patients and pave the way for a head-to-head comparison of DOACs with traditional therapy in this clinical setting. However, they underline that almost all the available data are derived indirectly from subgroup analyses of randomized trials including very few and highly selected patients with cancer, and that no studies specific to the cancer population have been concluded so far. In particular, further trials are eagerly awaited to evaluate the safety and efficacy of DOACs against LMWHs, which are currently the standard of care of VTE in cancer patients and are known to exert a specific anti-cancer activity beyond their antithrombotic effect. As such, the very limited data in cancer patients do not support the use of DOACs over LMWHs and until the result of cancer-specific studies in VTE treatment and prevention provide robust evidence on their safety and efficacy, the potential therapeutic value of DOACs in the cancer setting remains to be defined.

tabel1

Table. Randomized clinical trials evaluating DOACs in the treatment or prevention of cancer-associated VTE.

Reference

  1. Franchini M, Bonfanti C, Lippi G, et al. Cancer-associated thrombosis: investigating the role of new oral anticoagulants. Thromb Res 2015; Epub ahead of print.

 

scotte-350Previous studies, mainly from the US, indicate that the annual average cost per patient is significantly higher in cancer patients with VTE than in patients without VTE. These American studies indicate that healthcare costs are significantly higher in patients with VTE ($110,719 vs. $76,804, respectively, p< 0.0001) (Lyman et al, Oncologist 2012). In addition, complications (e.g. bleedings) and recurrences are frequent, resulting in additional costs. In fact, the cost of a recurrent thrombosis can be as high as $15,000 in the US (Bullano et al, J Manag Care Pharm 2005). Unfortunately, these data are not easily applicable to other countries, due to differences in patients and treatment pathways and in costs of hospital admissions and treatments. A recently reported French study aimed at determining the number of hospital admissions related to VTE occuring in patients with breast cancer (BC) or prostate cancer (PC) and calculated the associated hospital costs.

The published study included 62,365 and 45,551 patients diagnosed with BC and PC, respectively, in 2010. Of these populations, 1,271 (BC: 2.0%) and 997 (PC: 2.2%) were hospitalized for, or experienced a VTE during hospitalization. During the 2 years of follow-up, 346 patients (15%) presented a recurrence of thrombosis requiring hospitalization. A total of 1,604 and 1,210 inpatient VTE-related admissions were analyzed in the BC and PC cohorts, respectively. The mean cost per admission was € 3,302 and € 2,916 for a first event and a recurrence in BC patients (total cost: € 1.98 million over 2 years) and € 3,611 and € 3,363 in PC patients (total cost € 1.43 million over 2 years). In patients who had at least one recurrence, the mean hospitalization cost was € 5,545 and € 5,692 in BC and PC, respectively.

This study confirms that the healthcare burden of VTE is important, with about 2800 hospital admissions. The cost of this appeared to be substantial, close to € 3,4 million dedicated over 2 years to the management of a single complication in quite a small population (107,000 patients). Considering that the mean yearly expenditure for a patient with cancer is € 10,000,- it can be concluded that VTE increased the cost of management by nearly € 1,500 per year per patient with cancer. The authors of this study conclude that every effort should be made to prevent thromboembolic events by an appropriate prophylaxis and to avoid recurrences using an adequate and prolonged curative treatment and a good follow-up of recommendations.

Figure. Mean costs per hospital admission and per patient, for first venous thromboembolic event and recurrences.

figure-costs

 

Reference

Scotte F, Martelli N, Vainchtock A, et al. The cost of thromboembolic events in hospitalized patients with breast or prostate cancer in France. Adv Ther 2015;32:138-47.


 

AppApp-iconBased on international guidelines published in 2013, this app is a practical, step-by-step guide for the prophylaxis and treatment of venous thromboembolism in patients with cancer, including:
- Prophylaxis in hospitalized and ambulatory patients
- Treatment guidance for both non-catheter and catheter-related VTE
- Specific guidance related to various cancer and treatment types
- Early, short-term, and long-term treatment guidance

This treatment algorithm is intended for physicians and other healthcare professionals treating patients with cancer. It should not replace clinical judgement. It is based on two clinical practice guidelines published in 2013:

  1. Farge D, Debourdeau P, Beckers M, et al. International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. J Thromb Haemost. 2013;11(1):56-70.
  2. Debourdeau P, Farge D, Beckers M, et al. International clinical practice guidelines for the treatment and prophylaxis of thrombosis associated with central venous catheters in patients with cancer. J Thromb Haemost. 2013;11(1):71-80.

APP AUTHORS / STEERING COMMITTEE:

  • Professor Dominique Farge (France) (Co-chairperson)
  • Dr Philippe Debourdeau (France) (Co-chairperson)
  • Professor Henri Bounameaux (Switzerland)
  • Professor Benjamin Brenner (Israel)
  • Professor Harry Büller (the Netherlands)
  • Professor The Lord Ajay Kakkar (United Kingdom)
  • Professor Ingrid Pabinger-Fasching (Austria)
  • Dr Michael Streiff (United States)

ABOUT ITAC-CME

The International Initiative on Thrombosis and Cancer (ITAC-CME) is the international section of the Groupe Francophone Thrombose et Cancer (GFTC). A multidisciplinary group, the members of ITAC-CME are clinicians and researchers from across the globe, led by a core group of GFTC members. The mandate of ITAC-CME is to publish results of educational knowledge transfer research findings.

Through education of physicians, nurses, and allied health professionals, ITAC-CME is committed to disseminating relevant and peer-reviewed prophylaxis and treatment guidelines for VTE in cancer that will help to reduce a substantial economic burden on health care systems and improve the lives of millions of patients worldwide.


 

video-350Professor Ismail Elalamy’s practical threefold advice for the daily management of cancer-associated thrombosis:

  1. treat patients early,
  2. treat everybody who is in need of treatment
  3. and treat them long enough!