What is the role of Direct Oral Anticoagulants (DOACs) in cancer?

From the Guidelines

Direct oral anticoagulants (DOACs) are recommended for cancer patients with venous thromboembolism (VTE), with apixaban and rivaroxaban being preferred options due to their efficacy and safety profiles, as supported by recent guidelines and studies 1.

Key Considerations

• DOACs offer advantages over traditional low molecular weight heparin (LMWH) including oral administration, no need for monitoring, and fewer drug interactions.
• Caution is needed in patients with severe renal impairment, active GI or genitourinary malignancies, and those on medications that strongly affect P-glycoprotein or CYP3A4 pathways.
• Regular assessment of renal function, bleeding risk, and drug interactions is essential.

Treatment Duration and Dosing

• Treatment with DOACs should typically continue for at least 6 months, with consideration for extended therapy in patients with active cancer.
• Apixaban can be dosed at 5mg twice daily, while rivaroxaban can be dosed at 15mg twice daily for 21 days, then 20mg once daily.

Guidance for Specific Patient Populations

• For ambulatory cancer patients starting chemotherapy with a Khorana score ≥ 2, DOACs can be considered for primary thromboprophylaxis if there are no drug-drug interactions and the patient is not at high risk for bleeding 1.
• In patients with high-risk ambulatory cancer where primary thromboprophylaxis is planned but with concerns for safety of DOAC, low molecular weight heparin (LMWH) can be considered as an alternative 1.

From the Research

Role of Direct Oral Anticoagulants (DOACs) in Cancer

• The efficacy and safety of DOACs in the treatment of cancer-associated venous thromboembolism (CAVTE) have been evaluated in several studies 2, 3, 4, 5, 6.
• DOACs have been shown to be effective in preventing the occurrence of CAVTE, with a lower rate of recurrence VTE compared to low molecular weight heparin (LMWH) 2, 5.
• However, the risk of major bleeding and clinically relevant nonmajor bleeding was found to be higher with DOACs compared to LMWH 2, 4, 6.
• The choice of anticoagulant therapy should be individualized, taking into account the patient's risk of bleeding and recurrence of VTE, as well as their cancer type and treatment 3, 6.
• Apixaban has been shown to have a lower risk of bleeding events compared to other DOACs, and may be a preferred option for patients with cancer-associated VTE 2, 6.
• Edoxaban has been found to have a higher risk of major bleeding, but may provide a good risk-to-benefit balance in terms of preventing recurrence VTE 6.
• The National Comprehensive Cancer Network (NCCN) guidelines recommend the use of DOACs, including apixaban, edoxaban, and rivaroxaban, for the treatment of cancer-associated VTE, except in patients with gastric or gastroesophageal lesions 3.

Patient Selection and Controversies

• Patient selection for treatment with DOACs should take into account their individual risk factors, including cancer type, treatment, and history of bleeding or VTE 3, 6.
• The use of DOACs in patients with gastrointestinal and genitourinary cancers should be approached with caution, due to the increased risk of major bleeding 2, 3.
• The role of DOACs in the treatment of cancer-associated VTE is still evolving, and further studies are needed to fully understand their efficacy and safety in this population 4, 5, 6.

Efficacy and Safety Outcomes

• The efficacy of DOACs in preventing recurrence VTE has been consistently demonstrated across several studies, with a significant reduction in the risk of recurrence VTE compared to LMWH 2, 5, 6.
• The safety of DOACs has been evaluated in terms of major bleeding, clinically relevant nonmajor bleeding, and all-cause mortality, with varying results across studies 2, 4, 5, 6.
• The net clinical benefit of DOACs in patients with cancer-associated VTE has been found to be favorable, with a good risk-to-benefit balance, especially with edoxaban 6.