DOACs Useful Alternative for Treating Cancer-Associated VTE

By Will Boggs MD

April 17, 2019

NEW YORK (Reuters Health) - Direct oral anticoagulants (DOACs) can be a safe alternative to low-molecular-weight heparin (LMWH) for treating cancer-associated venous thromboembolism (VTE), according to a new review.

The annual incidence of VTE in cancer patients can be as high as 20%. Most guidelines currently recommend LMWH as first-line treatment for short- and long-term management of cancer-associated VTE.

Dr. Cihan Ay of the Medical University of Vienna and colleagues examined the existing evidence and possible issues regarding DOACs for treatment of VTE in patients with cancer in their review of current guidelines and newly published and ongoing studies.

Available evidence suggests that DOACs are noninferior to vitamin K antagonists and possibly comparable to LMWH in efficacy and safety for treating cancer-associated VTE, the team notes in the Annals of Oncology, online March 27.

Observational studies suggest that VTE recurrence rates are lower with DOACs than with LMWH and that rates of major bleeding are higher with DOACs than with LMWH only in patients with gastrointestinal or gynecological cancers.

Results from two randomized trials show that the DOACs edoxaban and rivaroxaban are equally or more effective for prevention of VTE recurrence but confer a higher risk for major bleeding relative to the LMWH dalteparin in patients with cancer, especially gastrointestinal cancer.

DOAC therapy may not be feasible in patients with chemotherapy-induced nausea and vomiting, they require careful dosing in patients with renal impairment, and drug-drug interactions may result from their effects on cytochrome 450 3A4.

There are limited data on the treatment of cancer-associated VTE in elderly patients and patients with renal impairment, but available information suggests that additional monitoring may be appropriate for such patients.

"In light of these data," the researchers note, "the International Society on Thrombosis and Haemostasis (ISTH) Scientific and Standardization Committee (SSC) 2018 guidance suggests edoxaban or rivaroxaban for cancer patients with an acute diagnosis of VTE, low risk of bleeding, and no drug-drug interactions with current systemic therapy, after shared decision-making with patients to balance potential reduction in VTE recurrence vs higher bleeding rates."

"The 2018 National Comprehensive Cancer Network guidance prefers LWMH monotherapy," they add, "but suggests DOAC use in patients for whom long-term LMWH therapy is not an option; they note that further investigation in cancer patients is needed for apixaban and dabigatran."

The authors conclude that "DOACs appear to be reasonable and often preferable alternatives to LMWH for management of VTE in patients with cancer without potential drug-drug interactions with chemotherapy or high risk for bleeding, especially when patient preference or practical considerations threaten persistence with LMWH therapy."

They provide a treatment algorithm based on current treatment guidelines and the new evidence summarized in their review.

Dr. Muthiah Vaduganathan from Brigham and Women's Hospital and Harvard Medical School, in Boston, who recently reviewed anticoagulation strategies in patients with cancer, told Reuters Health by email, "For patients with active non-gastrointestinal or non-genitourinary luminal cancers without significant drug-drug interactions, non-vitamin-K oral anticoagulants (i.e., DOACs) appear to be safe and appropriate anticoagulation approaches in the treatment of cancer-associated VTE."

"The pendulum appears to have swung for use of non-vitamin-K oral anticoagulants in the treatment of patients with cancer-associated VTE," said Dr. Vaduganathan, who was not involved in the new study. "Given the favorable tolerability, improved adherence profile, and lack of need for burdensome injections, non-vitamin-K oral anticoagulants will likely be preferred for many patients in clinical practice."

"The review briefly discusses prevention of index VTE in the cancer population," he said. "With 2 recently completed modest-sized trials suggesting potential benefits of non-vitamin-K oral anticoagulants in VTE prevention in at-risk populations, clinicians may consider non-vitamin-K oral anticoagulants in these select high-risk scenarios."

He added, "Although this review specifically discusses cancer-associated VTE, anticoagulation decision-making also occurs frequently in patients with cancer and concurrent atrial fibrillation/flutter. Large subgroup analyses from primary trials have supported the preserved safety and efficacy of non-vitamin-K oral anticoagulants in this population."

Daiichi Sankyo, Inc., which sells DOACs, funded the review and provided honoraria for all three authors of the report.

Dr. Ay did not respond to a request for comments.


Ann Oncol 2019.


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