Understanding Oral Anticoagulants in Cancer Treatment

An analysis of the EINSTEIN DVT and EINSTEIN PE clinical trials showed that the new oral anticoagulant rivaroxaban (Xarelto) was more effective and safer than a two-drug combination of low-molecular-weight heparin (LMWH) and a vitamin K antagonist (VKA) in the treatment and prevention of recurrent venous thromboembolism in patients with cancer. The results of the EINSTEIN clinical trial program support the suitability of Xarelto monotherapy for these medically vulnerable patients.

On September 27, 2014, the pharmaceutical company Bayer officially presented the results of the EINSTEIN clinical trial program at the European Society for Medical Oncology Congress, held in Madrid, Spain, from September 26 to 30. The announcement was published in The Lancet Haematology on September 28.

It was found that monotherapy with the oral anticoagulant rivaroxaban (Xarelto) was effective and safer for treating venous thromboembolism (VTE) in patients with cancer than treatment with a combination of injectable enoxaparin (Clexane) and a VKA.

Patients with active cancer or a history of cancer account for 10–20% of patients who experience VTE, including deep vein thrombosis (DVT) or pulmonary embolism (PE). Anticoagulant treatment in these patients is always challenging for physicians. Long-term VKA therapy carries a risk of major bleeding or recurrent VTE.

The ESMO Clinical Practice Guidelines for the treatment of VTE in patients with cancer recommend long-term treatment with injectable LMWH rather than a VKA. However, in daily clinical practice, contrary to these recommendations, patients are often prescribed an oral VKA instead because of economic and medical considerations and the potential for a better quality of life.

Comparison of Rivaroxaban and LMWH

Dr. Martin H. Prins, head of the EINSTEIN clinical trial program at Maastricht University Medical Center in the Netherlands, states that rivaroxaban has significant advantages over LMWH in long-term treatment: it does not require injections, its dosage does not depend on the patient’s body weight, and it does not carry the risk of heparin-induced thrombocytopenia.

According to EINSTEIN data, the efficacy and mortality outcomes associated with rivaroxaban were similar to those observed with injectable LMWH, while major bleeding complications occurred significantly less often.

According to Dr. M. H. Prins, rivaroxaban is a suitable alternative for patients with cancer and VTE in whom physicians are planning long-term VKA therapy rather than LMWH.

Dr. Michael Devoy, a member of the Executive Committee of Bayer HealthCare, the company that developed rivaroxaban (Xarelto), and Head of its Medical Department, emphasizes that the EINSTEIN program has expanded scientists’ and physicians’ understanding of the benefits of rivaroxaban for patients with cancer and DVT or PE. Based on the study data, Xarelto provides effective and safer anticoagulant treatment for these patients.

The EINSTEIN program forms part of a large ongoing evaluation of rivaroxaban involving more than 275,000 patients in clinical research and routine clinical practice.

About EINSTEIN DVT and EINSTEIN PE

The EINSTEIN DVT and EINSTEIN PE studies included patients with active cancer and VTE (n = 462), patients diagnosed with cancer during the studies (n = 193), and patients without active cancer but with a history of cancer (n = 469).

In the first two groups, rivaroxaban provided significantly greater benefits than the combination of enoxaparin and a VKA:

• It caused significantly fewer major bleeding events: 2.3% and 5.0% of patients, respectively.
• It had a more favorable combined clinical efficacy and safety outcome: recurrent VTE and major bleeding occurred in 4.5% and 6.6% of patients in the two treatment groups, respectively.
• Mortality rates were similar between the groups: 16.4% in the rivaroxaban group and 17.6% in the two-drug combination group.

About the EINSTEIN Clinical Trial Program

The EINSTEIN clinical trial program, involving nearly 12,000 patients, included four Phase III clinical trials: EINSTEIN DVT, EINSTEIN PE, EINSTEIN EXT, and EINSTEIN CHOICE.

The EINSTEIN DVT and EINSTEIN EXT data were published in the New England Journal of Medicine in 2010, while the results of EINSTEIN PE were published in Thrombosis Journal in November 2013.

Rivaroxaban was the first oral medication approved and introduced into clinical practice as monotherapy for the treatment of DVT and PE, as well as for the prevention of VTE in adults.

Among the new oral anticoagulants, rivaroxaban has the largest number of clinical indications, with approval for five clinical indications across eight therapeutic areas. It protects against venous and arterial thromboembolism in a wider range of conditions than other oral anticoagulants:

• Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and one or more risk factors.
• Treatment of deep vein thrombosis.
• Treatment of pulmonary embolism.
• Prevention of recurrent deep vein thrombosis.
• Prevention of recurrent pulmonary embolism.
• Prevention of venous thromboembolism in patients undergoing elective knee arthroplasty.
• Prevention of atherothrombotic complications, including myocardial infarction, stroke, or sudden death, after acute coronary syndrome in patients with elevated cardiac biomarkers when administered together with acetylsalicylic acid or with acetylsalicylic acid plus clopidogrel or ticlopidine.

Rivaroxaban has been approved for these indications in 125 countries worldwide.

Prepared by Dr. J. Kastys

Source: Lietuvos gydytojo žurnalas