What is the role of Direct Oral Anticoagulants (DOAC) in the management of Pulmonary Embolism (PE) in a patient with lung cancer and brain metastases?

From the Guidelines

The use of direct oral anticoagulants (DOACs) is not recommended as the first-line treatment for pulmonary embolism (PE) in patients with lung cancer and brain metastases due to the increased risk of major bleeding, and low molecular weight heparin (LMWH) is preferred in settings with an increased risk for bleeding. When considering anticoagulation therapy in patients with cancer, it is essential to weigh the benefits of preventing recurrent venous thromboembolism (VTE) against the risks of bleeding, particularly in those with brain metastases 1.

Some key points to consider when making this decision include:

• The risk of major bleeding with DOACs, particularly in patients with gastrointestinal malignancies, as seen in the study by Key et al, where 12.7% of patients with a GI malignancy experienced major bleeding compared with 3.6% of patients in the dalteparin arm (P = .005) 1.
• The results of the SELECT-D trial, which showed that the 6-month risk of VTE recurrence was 4% with rivaroxaban and 11% with dalteparin, but the risk of major bleeding was not significantly different between study arms 1.
• A meta-analysis by Brunetti et al, which found that DOACs were similar to LMWH with respect to recurrent VTE but had a higher risk of bleeding (OR, 2.72; 95% CI, 1.05 to 7.01) 1.
• The ASCO clinical practice guideline update, which recommends particular caution for DOAC use in settings associated with an increased risk for bleeding, such as patients with unresected mucosal tumors or active mucosal lesions, and suggests that LMWHs are currently preferred in these settings 1.

In patients with brain metastases, the risk of intracranial hemorrhage (ICH) must be carefully considered, and while observational data suggest that patients with CNS metastases have a lower risk of ICH on pharmacologic anticoagulation than patients with primary CNS malignancies, the presence of a stable or active primary intracranial malignancy or brain metastases is not an absolute contraindication to anticoagulation 1.

However, the decision to use DOACs in patients with lung cancer and brain metastases should be made on a case-by-case basis, taking into account the individual patient's risk factors for bleeding and the potential benefits of anticoagulation therapy, and regular monitoring for bleeding complications is essential, especially in the first few weeks of treatment 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Use of DOAC in PE in Patients with Lung Cancer and Brain Metastases

• The use of direct oral anticoagulants (DOACs) in patients with lung cancer and brain metastases who develop pulmonary embolism (PE) is a complex issue, with limited direct evidence available 2, 3, 4.
• A study published in 2023 found that DOACs were associated with a significantly reduced risk of VTE recurrence and deep vein thrombosis compared to low-molecular-weight heparin (LMWH) in cancer-associated thromboembolism, but there was no significant difference in the risk of pulmonary embolism between the two groups 3.
• Another study published in 2024 found that the risk of intracranial hemorrhage (ICH) in patients with brain cancer treated with DOACs versus LMWH varied by anticoagulation agent and diagnosis of primary or metastatic disease, with a reduction in risk of ICH with DOACs in primary brain cancer, but no difference in metastatic brain cancer 4.
• A case series study published in 2012 found that low molecular weight heparin (LMWH) can be safely used in cancer patients with hypercoagulability-related complications and brain metastases, with no cases of intracranial hemorrhage reported 2.
• The use of DOACs in patients with lung cancer and brain metastases who develop PE may be considered, but it requires careful evaluation of the individual patient's risk factors and close monitoring for potential complications, such as intracranial hemorrhage 5, 6.

Key Considerations

• The risk of intracranial hemorrhage in patients with brain metastases who receive anticoagulation therapy is a major concern, and the choice of anticoagulant should be individualized based on the patient's specific risk factors 2, 4.
• DOACs may be a viable option for patients with lung cancer and brain metastases who develop PE, but their use requires careful consideration of the potential risks and benefits, including the risk of intracranial hemorrhage and other bleeding complications 3, 6.
• Further studies are needed to fully evaluate the safety and efficacy of DOACs in this patient population, and to determine the optimal anticoagulation strategy for patients with lung cancer and brain metastases who develop PE 5, 4.