Lead Investigator: Mathilde Nijkeuter, University Medical Center Utrecht
Title of Proposal Research: Assessing bleeding risk in patients with cancer-associated thrombosis
Vivli Data Request: 5095
Funding Source: Yes; University Medical Center Utrecht, Utrecht, the Netherlands
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Venous thromboembolism (VTE) comprises deep vein thrombosis (DVT) and pulmonary embolism (PE). In DVT, a blood clot blocks a vein in the leg, whereas in PE, a vessel in the lung is blocked. VTE is a major complication among cancer patients, occurring in 4-20% of cancer patients. Anticoagulation is the cornerstone of treatment for cancer-associated thrombosis (CAT). CAT is associated with higher risks of both recurrent VTE and bleeding complications than usual, and risks are highly variable between patients. Therefore, finding the optimum treatment for individual patients with CAT is challenging. Guidelines advise to treat patients with active cancer and VTE for at least 3-6 months to prevent thrombus enlargement, embolization and early recurrence. Continuing anticoagulant treatment minimizes the risk of late recurrent VTE, but comes at the cost of a risk of major bleeding. These major bleedings comprise, among others, intracranial bleeds and bleeding of an internal organ. Therefore, guidelines recommend to consider extended treatment only in those with persisting risk factors for recurrent VTE and a low risk of bleeding.
Daily injections of low molecular weight heparin (LMWH) have been standard of care in the past 15 years. Nowadays, direct oral anticoagulants (DOACs) edoxaban and rivaroxaban, which can be given as tablets, are increasingly prescribed. Their use is advised in patients with a low risk of bleeding and no drug-drug interactions with other treatment. Thus, estimated risk of bleeding plays an important role in deciding on treatment for CAT. Several risk scores for bleeding during anticoagulation have been developed or validated in patients with VTE. Cancer is a predictor in many of these models. This suggests that the models also apply to the CAT population. However, as baseline risk of bleeding is higher and both cancer and treatment may have a profound impact on bleeding risk, it is unclear whether these models may indeed be generalizable to patients with CAT. Up till present, none of these models have been validated in patients with CAT, nor do specific cancer-related bleeding risk scores exist. How to assess risk of bleeding in patients with CAT across different stages of the cancer journey is currently unclear. This complicates not only clinical decision-making, but also patient education.
Insight into risk factors for bleeding during anticoagulant treatment for VTE in cancer patients is of vital importance. To provide directions for further research and guidance for clinical practice, a head-to-head comparison of all published prognostic models for bleeding in one dataset is warranted. In addition, insight in risk factors for bleeding in different stages of the cancer journey is needed to allow for more individualized decision-making. A new bleeding risk score may be required to adequately assess bleeding risk in patients with CAT.
A Phase 3b, Prospective, Randomized, Open-label, Blind Evaluator (PROBE) Study Evaluating the Efficacy and Safety of (LMW) Heparin/Edoxaban Versus Dalteparin in Venous Thromboembolism Associated With Cancer
Sponsor: Daiichi Sankyo, Inc.
Study ID: NCT02073682
Sponsor ID: DU176b-D-U311