Bleeding risk doubled during concurrent VEGFR–TKI, anticoagulant therapy
medwireNews: The risk for clinically significant bleeding during concurrent treatment with VEGFR–tyrosine kinase inhibitors (TKIs) and factor Xa inhibitors is doubled when compared with factor Xa inhibitors alone, research shows.
The study, among 86 patients (median age 56 years, 70% men) with metastatic cancer, indicates that “[c]aution should be exercised and further research is warranted to understand how to safely administer concurrent treatment in this at-risk population,” say Ming Yin (The Ohio State University College of Medicine, Columbus, USA) and co-investigators.
The patients received one or more VEGFR–TKIs (pazopanib, sunitinib, sorafenib, axitinib, regorafenib, vandetanib, lenvatinib, or cabozantinib) and factor Xa inhibitors (low molecular weight heparin [LMWH] including enoxaparin or the direct oral anticoagulants [DOACs] rivaroxaban or apixaban) between 2010 and 2018 whilst undergoing treatment for a variety of cancers, including renal cell carcinoma (48.8%), sarcoma (23.3%), and colorectal cancer (11.6%). The patients required anticoagulation for deep vein thrombosis and/or pulmonary embolism, or atrial fibrillation.
During a median 63 days of follow-up, there were 29 clinically significant bleeding events (including eight major bleeding events) reported when the patients were receiving concurrent treatment and 17 clinically significant events (including four major bleeding events) when they were receiving factor Xa inhibitor therapy, with each patient acting as their own control.
As reported in Cancer, regression analyses showed that the risk for overall bleeding was a significant 2.45-fold higher during concurrent treatment than during treatment with factor Xa alone, while the risk for first‐onset bleeding was 2.23-fold higher.
Yin and team found that the median time to first bleeding event was 56 days during concurrent treatment and 72 days during factor Xa inhibitor monotherapy, and they note that the bleeding risks appeared to be highest during the first 3 to 4 months of concurrent treatment but were evenly distributed over the entire length of anticoagulation with factor Xa alone.
The researchers say: “These data have important clinical implications, suggesting a need for close monitoring in the early phase of concurrent treatment.”
Yin et al note that their findings are “driven primarily by data derived from patients treated with concurrent TKIs and LMWH, and therefore should be interpreted with caution when examining patients treated with concurrent TKIs and DOACs”
They therefore add that “further studies are needed to address the safety of concurrent TKIs and DOACs, especially in the current era, in which DOACs often are used as first-line anticoagulants in patients with cancer.”
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