Characteristics and Outcomes of Patients on Concurrent Direct Oral Anticoagulants and Targeted Anticancer Therapies – TacDOAC Registry

T.-F. Wang¹, L. Baumann Kreuziger², A. Leader^3,4, G. Spectre^3,4, M. Lim⁵, A. Gahagan⁶, R. Gangaraju⁶, K. Sanfilippo⁷, R. Mallick⁸, J. Zwicker⁹, M. Carrier¹

¹University of Ottawa at The Ottawa Hospital and Ottawa Hospital Research Institute, Ottawa, Canada, ²Blood Research Institute, Versiti, Department of Medicine Medical College of Wisconsin, Milwaukee, United States, ³Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel, ⁴Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel, ⁵Division of Hematology and Hematologic Malignancies, Department of Internal Medicine, University of Utah, Salt Lake City, United States, ⁶Division of Hematology/Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, United States, ⁷Division of Hematology, Washington University School of Medicine, Saint Louis, United States, ⁸Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada, ⁹Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, United States

Abstract Number: PB1091

Meeting: ISTH 2021 Congress

Theme: Venous Thromboembolism » Cancer Associated Thrombosis

Background: Cancer patients are increasingly prescribed direct oral anticoagulants (DOACs) and targeted anticancer therapies, but limited data are available on the outcomes during concurrent use.

Aims: We conducted an international registry through the SSC of ISTH to evaluate bleeding and thrombotic outcomes in patients receiving concurrent DOACs and targeted anticancer therapies.

Methods: Patients receiving concurrent DOACs and selected targeted anticancer therapies were included (mostly retrospectively) and followed for 6 months after the start of concurrent use. Data including patient and cancer characteristics, major bleeding, non-major bleeding events, venous or arterial thromboses were collected and analyzed. The primary outcome was major bleeding by ISTH criteria. Analyses considered death as a competing risk. Local ethics committee approved the study.

Results: 202 patients were included from six institutions in the United States and Israel: 134 with venous thromboembolism (VTE) and 73 with atrial fibrillation. The most common malignancies were hematologic (N=57, 28.2%), followed by breast (N=50, 24.8%) and lung (N=44, 21.8%). The most common anticancer therapies were EGFR and ALK inhibitors (N=43, 21.3%), followed by BTK inhibitors (N=42, 20.8%) and palbociclib (N=42, 20.8%). During the 6-month follow up, there were 9 major bleeding and 12 non-major bleeding events, corresponding to cumulative incidences of 4% (95% confidence interval [CI]: 2-8%) and 6% (95% CI: 3-10%), respectively. The cumulative incidence of major bleeding events was highest in BTK inhibitor users (10%), followed by VEGF inhibitor users (7%) (Table and Figure). There were 3 VTE and 2 arterial thromboses, corresponding to cumulative incidences of 1.5% (95% CI: 0.4-4.0%) and 1.0% (95% CI: 0.2-3.3%), respectively.

Anticancer therapies (one patient was on palbociclib and everolimus at different time points)	N=202 (%)	Major bleeding		Non-major bleeding		Venous thromboembolism		Arterial thrombosis
		N (%)	Cumulative incidence %, (95% CI)	N (%)	Cumulative incidence %, (95% CI)	N (%)	Cumulative incidence %, (95% CI)	N (%)	Cumulative incidence %, (95% CI)
EGFR and ALK inhibitors (osimertinib, alectinib)	43 (21.3%)	1/43 (2.3%)	2 (0.2-11)	1/43 (2.3%)	2 (0.2-11)	0		1/43 (2.3%)	2 (0.2-11)
BTK inhibitors (ibrutinib, acalbrutinib)	42 (20.8%)	4/42 (9.5%)	10 (3-21)	6/42 (14.3%)	14 (6-27)	0		0
Cyclin-dependent kinase inhibitor (palbociclib)	42 (20.8%)	2/42 (4.8%)	5 (1-14)	3/42 (7.1%)	7 (2-18)	0		0
VEGF inhibitors (sunitinib, cabozantinib)	28 (13.9%)	2/28 (7.1%)	7 (1-21)	1/28 (3.6%)	4 (0.2-16)	2/28 (7.1%)	7 (1-21)	0
BCR-ABL inhibitors (imatinib, nilotinib)	22 (10.9%)	0		0		0		1/22 (4.6%)	5 (0.3-19)
mTOR inhibitor (everolimus)	18 (8.9%)	0		1/18 (5.6%)	6 (0.3-23)	0		0
HER2 inhibitors (lapatinib)	4 (2.0%)	0		0		0		0
BRAF inhibitors (dabrafenib, vemurafenib)	4 (2.0%)	0		0		1/4 (25%)	25 (0.3-71)	0

Outcomes by anticancer therapies
Cumulative incidence of major bleeding events by types of anticancer therapies

Conclusions: In this cohort receiving concurrent DOACs and targeted anticancer therapies, the incidence of bleeding is higher compared to thrombosis, particularly with selective anticancer therapies such as BTK inhibitors. Future larger prospective studies are needed for better assessment to improve care for these patients.

To cite this abstract in AMA style:

Wang T-, Baumann Kreuziger L, Leader A, Spectre G, Lim M, Gahagan A, Gangaraju R, Sanfilippo K, Mallick R, Zwicker J, Carrier M. Characteristics and Outcomes of Patients on Concurrent Direct Oral Anticoagulants and Targeted Anticancer Therapies – TacDOAC Registry [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/characteristics-and-outcomes-of-patients-on-concurrent-direct-oral-anticoagulants-and-targeted-anticancer-therapies-tacdoac-registry/. Accessed December 11, 2023.

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