EMERGING DATA FOR CANCER ASSOCIATED THROMBOSIS TREATMENT

Abstract

Venous thromboembolism (VTE) is a common complication in patients with malignancies,resulting in deep vein thrombosis, pulmonary embolism and central venous catheter VTE, and is responsible for high morbidity and mortality (1). The prevalence of cancer-associated thrombosis is increasing because of multiple factors, including longer patient survival, anticancer therapies, increased detection of incidental VTE during surveillance imaging, and wider use of central venous catheters. Anticoagulant therapy with low-molecular-weight heparins (LMWHs) was the standard of care for the treatment of cancer-associated thrombosis, with vitamin K antagonists providing a secondary treatment option, until direct oral anticoagulants (DOAC) emerged as alternative first-line treatment options in 2016 (2). Rivaroxaban, Edoxaban and Apixaban are recommended as initial treatment in patients with cancer-associated thrombosis who are not at high risk of gastrointestinal or genitourinary bleeding (3). LMWHs and Fondaparinux are still recommended for prophylaxis of VTE in medically-treated patients with cancer. Rivaroxaban and Apixaban can be used selectively for thromboprophylaxis in patients with malignancies at high risk of VTE, for example in patients with pancreatic cancer or myeloma (4,5). Anticoagulant choice should incorporate a personalised medicine approach that considers cancer type, VTE and bleeding risk factors, drug–drug interactions (DDI), and patient preferences. Patients with cancer often experience narrow therapeutic index polypharmacy and undergo treatment for several simultaneous comorbidities. In this setting the risk of DDI is high in particular during therapy with tyrosine kinase inhibitors (6). Concerns on DDI management include decreased efficacy and bleeding risk. In general, DOAC use is not advisable in combination with drugs that are strong inhibitors of both P-gp and/or CYP3A4 for high bleeding risk and in combination with strong inducers of Pgp and/or CYP3A4 that could markedly reduce DOAC plasma levels. Routine use of plasma level measurements for DOAC, only available in few laboratory centres, is not currently recommended (7). Nevertheless it has recently become increasingly clear that clinicians need to assess the anticoagulant status of a patient receiving anticancer therapies. The global coagulation Test of thrombin generation (TGT) a sensitive method to assess the anticoagulant therapy, provides a global measure of anticoagulant effect by measuring the inhibition of formation of thrombin (FIIa), a common endpoint for both LMWH and FXa inhibitors (8). Furthers studies are warranted to better define the future role of this coagulation test in this subgroup of patients.