Increased bleeding risk associated with concurrent vascular endothelial growth factor receptor tyrosine kinase inhibitors and low‐molecular‐weight heparin. Issue 6 (20th November 2020)

• Record Type: Journal Article
• Authors: Patel, Sandip H.; George, Tiffany L.; Wang, Tzu‐Fei; Vogt, Sherry M.; Folefac, Edmund; Xu, Menglin; Yang, Yuanquan; Parikh, Anish B.; Verschraegen, Claire F.; Clinton, Steven K.; Yin, Ming
• Is Part Of: Cancer. Volume 127:Issue 6(2021)
• Page Start: 938
• Page End: 945
• Publication Date: 2020-11-20
• Subjects: bleeding -- cancer -- direct oral anticoagulant (DOAC) -- factor Xa inhibitor -- low‐molecular‐weight heparin (LMWH) -- tyrosine kinase inhibitor -- vascular endothelial growth factor receptor (VEGFR); Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.33337
• Languages: English
• ISSNs: 0008-543X

Abstract

Abstract : Background: Some cancer patients who are diagnosed with thromboembolism may require dual treatment with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) and factor Xa inhibitors (low‐molecular‐weight heparin [LMWH] or direct oral anticoagulants [DOACs]). However, to the authors' knowledge, the safety of such combinations has not been well characterized. Methods: Patients with advanced cancer who were treated with concurrent VEGFR TKIs and factor Xa inhibitors between 2010 and 2018 at The Ohio State University Comprehensive Cancer Center were included. Charts were reviewed retrospectively for clinically significant bleeding events occurring during concurrent treatment compared with those occurring during factor Xa inhibitor therapy alone, using each patient as their own control. The Fisher exact test was used to compare distribution of bleeding severities. The Cox proportional hazards model was used to compare bleeding risk between groups. Results: Among 86 patients, there were 29 clinically significant bleeding events (including 8 major bleeding events) reported during concurrent treatment and 17 events (including 4 major bleeding events) reported during factor Xa inhibitor therapy alone over a median follow‐up of 63 days. Concurrent treatment was associated with significantly higher risks of overall bleeding (hazard ratio, 2.45; 95% confidence interval, 1.28‐4.69 [ P = .007]) and first‐onset bleeding (hazard ratio, 2.23; 95% confidence interval, 1.13‐4.42 [ P = .02]). Analysis of 6‐month bleeding risk and the subgroups of patients treated with concurrent TKIs and LMWH versus LMWH alone demonstrated a similar trend. The sample size was inadequate for comparisons between treatment with concurrent TKIs and DOACs versus DOACs alone. Conclusions: Concurrent treatment with VEGFR TKIs and LMWH was found to be associated with a significantly increased risk of bleeding events when compared with LMWH therapy alone. Abstract : The results of the current study suggest that there is an increased risk of bleeding with the concurrent use of vascular endothelial growth factor receptor tyrosine kinase inhibitors and factor Xa inhibitors in patients with metastatic cancer. Careful monitoring is required and future studies are warranted to further understand and assess how to safely administer concurrent treatment in this at‐risk population.