Latest advances in preventing thromboembolic disease in the ambulatory oncology patient

Abstract

Venous thromboembolism (VTE) is often cited as a major cause of death and morbidity in cancer patients. Even a non-lethal VTE causes distress and is commonly perceived by patients as a set-back in the cancer journey and a threat to the cancer treatment. It is also known that the risk of VTE varies between cancers (cancer-related risk factors), between patients (patient-related risk factors), and also within the cancer journey of a single patient. Risk can increase during treatments like surgery and chemotherapy and decline during remission. Neither the low molecular weight heparins nor the vitamin K analogues have gained an established role in thromboprevention guidance other than in 'the high risk' patient, who remains a rather ambiguous entity. The recently published randomised studies of rivaroxaban and apixaban in moderate- to high-risk thrombosis patients, assigned by the Khorana Risk Score, has seen the inclusion of direct oral anticoagulants (DOACs) in recent guidelines (e.g. the American Society of Clinical Oncology 2019 guidelines) for this indication. The ease of administration and the demonstrated greater patient adherence to oral agents has heightened the expectation that a practice-changing thromboprevention study in cancer patients should be realizable. However, key unmet needs that pose familiar challenges remain and as yet do not have satisfactory solutions. Anticoagulants carry risks of bleeding that are higher in the cancer population. There is therefore the challenge of sufficient risk reduction of VTE from the intervention balanced against the number of patients that may be harmed from bleeding. There is also the challenge of penetrating the risk threshold beyond which oncologists would deem thromboprevention a clinically meaningful praxis. Thus, identifying the high-risk groups of patients or targeting the length or timing of the thromboprevention to when the risks are highest are major questions that remain the subject of ongoing research. Notably all this is taking place against a backdrop of changing therapeutics for many cancers (e.g. targeted agents, checkpoint inhibitors and combinations) and their assorted impact on VTE incidence. In this review, past data for the ambulatory cancer patient are summarised, the latest evidence for the direct oral anticoagulants apixaban and rivaroxaban are analysed and the challenges of identifying the high-risk patients that have the greater chance of benefiting from thromboprophylaxis are discussed.

Keywords: Anticoagulants; Cancer-associated thrombosis (CAT); DOAC; Risk scoring model; Thromboprophylaxis; Venous thromboembolism (VTE).