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

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.

Direct oral anticoagulants versus low-molecular-weight heparins for the treatment of acute venous thromboembolism in patients with gastrointestinal cancer: a systematic review and meta-analysis

“…Furthermore, the heterogeneity of the meta-analysis was low, with an I2 value of 41% (Fig. 3 ) [ 11 , 20 – 24 , 26 – 29 ].

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“…In contrast, the incidence of CRNMB was significantly higher in the DOAC group than in the LMWH group, with a pooled RR of 1.76 (95% CI: 1.24–2.52; P = 0.002; I2 = 8%; Fig. 4 ) [ 11 , 21 , 22 , 24 , 28 , 29 ].

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“…Four studies reported the locations of major bleeding in patients with GI cancer treated with DOACs [ 22 , 24 , 29 , 30 ]. Of 50 bleeding events, 41 occurred in the GI tract.…”

“…The rates of recurrent VTE in patients who received DOACs and those who received LWMHs were not significantly different, with a pooled RR of 0.72 (95% CI: 0.49–1.04; P = 0.08; I 2 = 0%; Fig. 5 ) [ 20 , 21 , 23 , 25 – 27 , 29 ].

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“…The pooled RRs of major bleeding were 1.65 (95% CI: 0.89–3.08; P = 0.11; I2 = 27%; Fig. 3 ) [ 11 , 20 , 24 , 26 , 29 ]. The rate of CRNMB was significantly higher in the DOAC group, with a pooled RR of 2.71 (95% CI: 1.43–5.14; P = 0.002; I2 = 0%; Fig.…”