Bayer Pharma AG


Investigational Strategies

Investigational Strategies

Clinical data on the novel oral direct Factor Xa inhibitors and direct thrombin inhibitors for the prevention of venous thromboembolism (VTE) and the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients with cancer are relatively limited. Clinical trials of the novel oral anticoagulants involving patients with cancer include the phase III MAGELLAN trial, which investigated rivaroxaban for VTE prevention in medically ill patients, the phase III studies of novel oral anticoagulants for the treatment of DVT and PE, and a phase II trial of apixaban in patients with metastatic cancer (NCT00320255). Pooled data from the EINSTEIN DVT and EINSTEIN PE trials have shown reassuring efficacy and safety for rivaroxaban compared with LMWH/VKA therapy in patients with cancer, and similar outcomes have been observed with other novel oral anticoagulants. An ongoing prospective clinical study programme is investigating the efficacy and safety of rivaroxaban compared with LMWH in patients with cancer.


Guideline Recommendations

A number of guidelines have been published for the prevention of venous thromboembolism (VTE) and treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients with cancer. A consensus on guidelines for the use of antithrombotic therapy for VTE in patients with cancer, and their implementation in clinical practice, may assist in improving the care that patients with cancer receive.


Balancing the risks and benefits of anticoagulation in patients with cancer

Bleeding complications associated with anticoagulation therapy have been shown to be more frequent in patients with cancer than in those without cancer. Striking a balance between the risk of bleeding and the benefits of anticoagulant therapy in patients with cancer is, therefore, particularly important. The 2012 American College of Chest Physicians (ACCP) guidelines identify several factors that, in patients at a high risk of bleeding, indicate a lower risk of recurrence of venous thromboembolism (VTE) in patients with cancer, and may support stopping anticoagulant therapy.


Treatment of deep vein thrombosis and pulmonary embolism

Anticoagulant treatment in patients with cancer with venous thromboembolism (VTE) can be a challenge as treatment may often be interrupted by invasive procedures or thrombocytopenia caused by chemotherapy. Oral vitamin K antagonists (VKAs) may not always be appropriate in patients with cancer; low molecular weight heparins (LMWHs), in addition to unfractionated heparin (UFH) and fondaparinux, are, therefore, preferred for patients with cancer. The risk of recurrent VTE is higher in patients with cancer than in those without and can depend on a number of factors including: the presence of metastatic cancer; treatment with chemotherapy; and the type of cancer.


Venous thromboembolism prevention in patients with cancer

Low molecular weight heparins (LMWHs) and unfractionated heparin (UFH) have been shown to have similar efficacy for thromboprophylaxis in patients with cancer. Both agents are recommended by the 2012 American College of Chest Physicians (ACCP) guidelines for thromboprophylaxis in patients with cancer who are at increased risk of venous thromboembolism (VTE). Vitamin K antagonists (VKAs) and fondaparinux are two other options for the prevention of VTE in patients with cancer. Although some clinical studies have demonstrated a benefit for thromboprophylaxis in hospitalized and surgical patients with cancer, it is not routinely recommended for ambulatory cancer patients. Despite the guideline recommendations, adequate VTE prophylaxis is currently underused in patients with cancer.


Cancer increases the risk of venous thromboembolism

Patients with cancer face an increased risk of venous thromboembolism (VTE) as malignancy is associated with a hypercoagulable state and the use of chemotherapy agents may also contribute to an increased risk. In fact, VTE is a significant cause of morbidity and mortality in patients with cancer. Risk factors for cancer-associated VTE include: tumour type; age; stage of cancer; and VTE history. Risk stratification and use of biomarker-based approaches may assist in the provision of targeted thromboprophylaxis. The use of a validated predictive model for VTE risk in patients with cancer receiving chemotherapy may also enable clinicians to determine whether patients are at particularly high risk of VTE.