Safety of Doacs in Patients with CNS Malignancies

Abstract

Background: Neuro-oncology patients, like all cancer patients, are at a high risk for thromboembolic complications and frequently require treatment with anticoagulation. DOACs have emerged as a less burdensome treatment for cancer associated thrombosis with comparable safety and efficacy to LMWH. Unfortunately, there is a paucity of data to support the use of DOACs in patients with primary and metastatic brain tumors and there is concern in the medical community for increased risk of intracranial hemorrhage. Objectives: The purpose of this study is to better understand the safety profile of anticoagulants in brain tumor patients, with a particular interest in the safety and efficacy of DOACs. Our hypothesis is that DOACs are as safe and effective as LWMH in this patient population. Methods: This study was conducted through retrospective chart review of patients with primary and metastatic brain tumors on anticoagulation. Our outcomes of interest were major bleeding (as defined by ISTH guidelines), with particular interest in Intracranial hemorrhage as well as minor bleeding and recurrent thrombosis. Radiographic images of all patients were reviewed for evidence of ICH and CTCAE v5 criteria were used to grade severity of ICH cases with range from 1 (asymptomatic imaging finding) to 5 (death). Results and Conclusions: A total of 130 patients with brain tumors were evaluated (69% primary brain tumor, 15% CNS lymphoma, 16% metastatic disease). Out of this population, 62 were on LMWH and 52 were on DOACs. The incidence of major bleeding was 20.9% in the LMWH group vs. 9.6% in the DOAC group (P =0.1, 95% CI -2.45 - 24.1). The incidence of ICH was 14.5% in the LMWH group and 5.8% in the DOAC group (P =0.13 95% CI -3.23 - 20.2). The severity of ICH in both groups was low with median CTCAE v5 scores of 2 in LMWH group and 3 in the DOAC group. The incidence of minor bleeding was 16.1% in LMWH group and 21.1% in the DOAC group (P = 0.49 CI -9.2 - 19.7). Recurrent thrombosis in both groups occurred in <5% of cases. Our conclusion is that in patients with primary and metastatic brain tumors, DOACs are not associated with an increased incidence of major bleeding or ICH compared to LMWH and are a safe and effective option in this patient population. Disclosures No relevant conflicts of interest to declare.

Clinical controversies in the treatment of cancer-associated venous thromboembolism

“…[25][26][27][28] 45 Finally, in a retrospective analysis of 114 patients (69% primary brain malignancy, 15% CNS lymphoma, 16% CNS metastases) receiving DOACs (n ¼ 52) or LMWH (n ¼ 62), DOAC patients experienced numerically lower rates of major bleeding (9.6% vs 20.9% [95% CI -2.45-24.1]; p ¼ 0.1) and intracranial hemorrhage (5.8% vs 14.5% [95% CI -3.23-20.2]; p ¼ 0.13) than patients on LMWH. 46 The results of these retrospective analyses may be influenced by selection bias in anticoagulant choice and detailed baseline characteristics have not yet been reported in the latter two analyses. 45,46 However, available data suggest that DOACs are not associated with an increased risk of bleeding or intracranial hemorrhage in patients with primary CNS malignancies or brain metastases.…”

“…46 The results of these retrospective analyses may be influenced by selection bias in anticoagulant choice and detailed baseline characteristics have not yet been reported in the latter two analyses. 45,46 However, available data suggest that DOACs are not associated with an increased risk of bleeding or intracranial hemorrhage in patients with primary CNS malignancies or brain metastases.…”