Retrospective Study of Bleeding Risk with Concomitant Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor and Anticoagulation

• Published in: The oncologist (Dayton, Ohio) Vol. 26; no. 11; pp. e2061 - e2069
• Main Authors: Sivakumar, Akhilesh, Caulfield, Sarah E., Zhang, Chao, Goyal, Subir, Bilen, Mehmet A., Beardslee, Tyler J.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-11-2021; Oxford University Press
• Subjects: Anticoagulants (Medicine); Anticoagulants - adverse effects; Anticoagulation; Antimitotic agents; Antineoplastic agents; Apixaban; Care and treatment; Complications and side effects; Demographic aspects; Diagnosis; Direct oral anticoagulant; Dosage and administration; Health aspects; Hemorrhage; Humans; Major bleed; Medical research; Medicine, Experimental; Minor bleed; Phenols; Protein Kinase Inhibitors - adverse effects; Receptors, Vascular Endothelial Growth Factor; Retrospective Studies; Risk factors; Rivaroxaban; Symptom Management and Supportive Care; Thromboembolism; Tyrosine; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A; VEGF TKI; United States; Anticoagulation; Minor bleed; Direct oral anticoagulant; Major bleed; VEGF TKI
• ISSN: 1083-7159; 1549-490X
• DOI: 10.1002/onco.13897

Background
Patients with cancer are at higher risk for venous thromboembolism (VTE) and bleeding, in turn complicating anticoagulant therapy. An added complexity is the toxicity profile of agents used to treat certain cancers, namely the vascular endothelial growth factor receptor tyrosine kinase inhibitors (TKIs), which are associated with both thromboembolism and hemorrhages. The purpose of this study was to evaluate whether patients taking concurrent VEGF TKI and therapeutic anticoagulant were at higher risk for bleeding compared with patients taking VEGF TKI alone.
Materials and Methods
This was a single‐center, retrospective chart review of patients who underwent treatment with a VEGF TKI with or without anticoagulant. The primary outcome included comparison of major bleeding rates between groups. Secondary outcomes included comparison of composite major and minor bleed rates and assessment of VTE incidence and recurrence among patients treated with a VEGF TKI and VEGF TKI plus anticoagulant, respectively.
Results
A total of 184 and 74 patients were included in the VEGF TKI alone and VEGF TKI + anticoagulant groups, respectively. Major bleeding events occurred in 6 of 184 patients (3.3%) and 6 of 74 patients (8.1%), respectively (p = .095). Composite major and minor bleeding events occurred in 22 of 184 (13.6%) and 17 of 74 (23%), respectively (p = .026). A total of 26 of 258 patients (10.1%) experienced a VTE event while taking a VEGF TKI, and 1 of 26 (3.8%) experienced a recurrent VTE event while taking a VEGF TKI plus anticoagulant.
Conclusion
Patients who received concomitant VEGF TKI plus anticoagulant had increased incidence of bleeding, although prospective studies are needed to further explore this association.
Implications for Practice
The current study showed that use of concomitant vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGF TKI) and therapeutic anticoagulation was associated with an increased risk of composite bleeding events, although at comparable rates between patients treated with VEGF TKI plus direct oral anticoagulant (DOAC) versus VEGF TKI plus non‐DOAC anticoagulant. This suggests that when anticoagulation is indicated in a patient receiving a VEGF TKI, the novel DOACs may be a safe alternative to historical anticoagulants (warfarin and enoxaparin). These results fill a gap in the literature and will help guide treatment decisions for patients requiring concurrent VEGF TKI and anticoagulation.
Patients with cancer are at higher risk for venous thromboembolism and bleeding, complicating anticoagulant therapy. This article assesses whether patients who received concomitant vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGF TKI) and anticoagulation were at higher risk for bleeding events compared with those who received a VEGF TKI alone.