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. 2022 Jan 22;14(3):559.
doi: 10.3390/cancers14030559.

A Phase II Study to Compare the Safety and Efficacy of Direct Oral Anticoagulants versus Subcutaneous Dalteparin for Cancer-Associated Venous Thromboembolism in Patients with Advanced Upper Gastrointestinal, Hepatobiliary and Pancreatic Cancer: PRIORITY

Jwa Hoon Kim  1   2 , Changhoon Yoo  1 , Seyoung Seo  1 , Jae Ho Jeong  1 , Baek-Yeol Ryoo  1 , Kyu-Pyo Kim  1 , Jung Bok Lee  3 , Keun-Wook Lee  4 , Ji-Won Kim  4 , Il-Hwan Kim  5 , Myoungjoo Kang  5 , Hyewon Ryu  6 , Jaekyung Cheon  7 , Sook Ryun Park  1
Affiliations

A Phase II Study to Compare the Safety and Efficacy of Direct Oral Anticoagulants versus Subcutaneous Dalteparin for Cancer-Associated Venous Thromboembolism in Patients with Advanced Upper Gastrointestinal, Hepatobiliary and Pancreatic Cancer: PRIORITY

Jwa Hoon Kim et al. Cancers (Basel). .

Abstract

Background: We evaluated the safety and efficacy of direct oral anticoagulants (DOACs) versus subcutaneous dalteparin for cancer-associated venous thromboembolism (CA-VTE) in patients with advanced upper gastrointestinal (GI) tract, hepatobiliary, or pancreatic cancer.

Methods: This was a multicenter, randomized, open-label, phase II trial in five centers. Patients randomly received rivaroxaban (15 mg twice daily for 3 weeks, then 20 mg once daily)/apixaban (10 mg twice daily for the first 7 days, then 5 mg twice daily) or dalteparin (200 IU/kg once daily for the first month, then 150 IU/kg once daily). Randomization was stratified by the Eastern Cooperative Oncology Group Performance Status, primary cancer type, active chemotherapy, and participating centers. The primary endpoint was the rates of clinically relevant bleeding (CRB) in the full analysis set (FAS).

Results: A total of 90 patients were randomly assigned to the DOAC (n = 44) and dalteparin groups (n = 46) in FAS. CRB and major bleeding (MB) rates were 34.1% and 13.0% (p = 0.018) and 18.2% and 4.3% (p = 0.047) for the DOAC and dalteparin groups, respectively. Time to CRB and MB was higher in the DOAC group than in the dalteparin group (hazard ratio [HR] 2.83; p = 0.031 and HR 4.32; p = 0.064). Cancer involvement at the GI mucosa was also a significant risk factor for CRB. Recurrent CA-VTE occurred in 2.3% and 2.2% of patients given DOAC and dalteparin, respectively (p = 1.000).

Conclusion: DOAC therapy further increased the risk of bleeding compared with dalteparin in patients with active advanced upper GI tract, hepatobiliary, or pancreatic cancer, suggesting that extra caution should be taken when selecting anticoagulants for CA-VTE.

Keywords: apixaban; dalteparin; gastrointestinal tract cancer; hepatobiliary cancer; pancreatic cancer; rivaroxaban; venous thromboembolism.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Consort diagram.
Figure 2
Figure 2
The Kaplan–Meier curves of the time to (A) clinically relevant bleeding (major and nonmajor bleeding), (B) major bleeding, (C) total events of bleeding, and (D) recurrent cancer-associated venous thromboembolism in full analysis set.
Figure 3
Figure 3
The Kaplan–Meier curves of the time to (A) clinically relevant bleeding (major and nonmajor bleeding), (B) major bleeding, (C) total events of bleeding, and (D) recurrent cancer-associated venous thromboembolism according to the administered drug during bleeding events in full analysis set.
See this image and copyright information in PMC

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