Safe and effective treatment of venous Thromboembolism associated with Cancer: focus on direct Oral Anticoagulants in Asian patients

Abstract

Cancer-associated thrombosis (CAT) poses a significant disease burden and the incidence in Asian populations is increasing. Anticoagulation is the cornerstone of treatment, but can be challenging due to the high bleeding risk in some cancers and the high risk of recurrent venous thromboembolism (VTE) in patients with malignancies. Direct oral anticoagulants (DOACs) are well established as first-choice treatments for VTE in non-cancer patients, offering a more convenient and less invasive treatment option than low-molecular-weight heparin (LMWH). Asian patients have exhibited comparable efficacy and safety outcomes with other races in trials of DOACs for VTE in the general population. Although no specific data are available in Asian patients with CAT, results from randomized controlled trials of apixaban, edoxaban, or rivaroxaban versus the LMWH, dalteparin, indicate that DOACs are a reasonable alternative to LMWH for anticoagulation in Asian patients with CAT. This is further supported by analyses of real-world data in Asian populations demonstrating the efficacy and safety of DOACs in Asian patients with CAT. Apixaban, edoxaban, or rivaroxaban are recommended in the most recently updated international guidelines as first-line therapy for CAT in patients without gastrointestinal or genitourinary cancers and at low risk of bleeding. An increased risk of major gastrointestinal bleeding was evident with edoxaban or rivaroxaban, but not apixaban, versus dalteparin in the clinical trials, suggesting that apixaban could be a safe alternative to LMWH in patients with gastrointestinal malignancies. Determining the optimal anticoagulant therapy for patients with CAT requires careful consideration of bleeding risk, tumor type, renal function, drug–drug interactions, financial costs, and patients’ needs and preferences.

Trends in Anticoagulant Utilization and Clinical Outcomes for Cancer-Associated Thrombosis: A Multicenter Cohort Study in Thailand's Upper-Middle–Income Country Setting

“…[6][7][8][9] However, it should be noted that the RCTs had strict inclusion criteria and a low representation of Asian patients, ranging from only 0.7% to 21.0% of trial participants. [6][7][8][9]14 Because of the lower incidence of CAT in Asian versus Western populations, especially those with advanced-stage diseases 22,23 and generally lower BMI, 24 the patients in these trials may not be representative of the Asian demographic in UMICs. Moreover, many RCTs exclude patients with advanced-stage cancer, severe comorbidities, or impaired organ function, which further limits their applicability.…”

The Role of Direct Oral Anticoagulants in the Treatment of Cancer-Associated Venous Thromboembolism: Review by Middle East and North African Experts

“… Notes : This table collates data from the cited published papers, 32–36 also over viewed in two previously published studies 55 , 56 and new data available since then. a Primary analysis population (n=145).…”

“… Notes : This table collates data from the cited published papers, 62–66 also over viewed in two previously published studies. 55 , 56 aDOACs versus LMWH. b ADAM VTE not included.…”

“… ESMO During the acute phase (first 5–10 days after diagnosis) Consider LMWH, UFH, fondaparinux, apixaban or rivaroxaban (I, A) LMWH is preferable to UFH and fondaparinux (V, A) For long-term anticoagulation for at least 6 months LMWH, apixaban, edoxaban or rivaroxaban are preferred to VKAs (I, A) In patients with luminal GI cancer, urothelial cancer (II, B), patients at high risk of GI bleeding, receiving powerful inducers and/or inhibitors of CYP3A4 or P-gp, (IV, B) LMWH is preferred. Beyond initial 6 months, LMWH, apixaban, edoxaban, rivaroxaban or VKAs based on benefit–risk assessment (III, B) Regularly assess risk–benefit profile of anticoagulation therapy for favorable balance (IV, C) Notes : This table collates data from the cited published papers, 31 , 37–42 , 69 , 72 also over viewed in two previously published studies 55 , 56 and new data available since then. a Recommendations based on ADAM VTE, Caravaggio, Hokusai VTE Cancer and SELECT-D trial results.…”

“… Notes : This table collates data from the cited published papers, 31 , 37–42 , 69 , 72 also over viewed in two previously published studies 55 , 56 and new data available since then. a Recommendations based on ADAM VTE, Caravaggio, Hokusai VTE Cancer and SELECT-D trial results.…”