Mar 152019

About one in five patients with cancer will develop pulmonary embolism (PE) or deep venous thrombosis (DVT), together called venous thromboembolism (VTE). Cancer patients who develop VTE are four times more likely to have experience another (recurrent) DVT or PE.

Twice-daily injections of enoxaparin are advised for patients with cancer-related DVT/PE, or who are at high risk for it, based on apparent superiority to warfarin. But injections are painful, inconvenient, and expensive, and the newer oral anticoagulants (if safe and effective) would be preferable. Evidence is mounting that may soon tip physicians and their advisory societies toward endorsement of newer oral anticoagulants (NOACs) in the treatment and prevention of DVT-PE in patients with cancer.

randomized trial suggested the NOAC edoxaban (sold as Savaysa) was noninferior to low-molecular weight heparin (dalteparin) in the treatment of cancer-associated venous thromboembolism. One caveat was higher rates of gastrointestinal bleeding in patients with GI cancers.

In another trial in the U.K. among >400 patients with cancer and a first diagnosis of VTE (~80% had DVT; ~20% PE), those treated with rivaroxaban had a 4% rate of recurrent VTE over 6 months, compared to 11% of those treated with enoxaparin. Major bleeding was about the same (6% with rivaroxaban, 4% with LMWH). Patients with GI cancers also were seen to have high rates of severe bleeding, and the trial stopped enrolling such patients midway through. There were no intracranial hemorrhages.

In the latest study, the NOAC apixaban beat placebo for prevention of DVT and PE in cancer patients.  From 2014 to 2018, 574 outpatients with cancer and a moderate to high risk of DVT/PE who were starting chemotherapy were randomized to either apixaban 2.5 mg twice daily or to placebo for six months. About 9% or patients had had DVT or PE previously.

Twelve patients taking apixaban experienced VTE (4.2%), compared with 28 patients (10.2%) in the placebo group. (hazard ratio, 0.41; 95% confidence interval [CI], 0.26 to 0.65; P<0.001).

That translated to a number needed to treat of 17 to prevent one PE or DVT, "driven predominantly by a lower rate of pulmonary embolism in the apixaban group," the authors wrote in the New England Journal of Medicine. Patients taking apixaban had about double the risk of significant bleeding (3.5% vs 1.8%). No fatal bleeding was observed, and most major bleeding occurred in patients with gastrointestinal or gynecologic cancer.

Apixaban's manufacturer's design of this trial for prevention rather than treatment of venous thromboembolism in cancer patients may prove to have been clever business-wise. If the drug wins an FDA indication for VTE prevention in cancer, millions of patients would be eligible for treatment, not just the small minority of them who actually develop DVT-PE.

Because of the substantial advantages of oral anticoagulants over enoxaparin injections, and the encouraging results of these trials, some hematologist-oncologists have already gravitated toward use of NOACs for treatment and prevention of DVT-PE in patients with non-gastrointestinal cancer. Expect advisory societies to consider the data in guideline updates in the near future.

Source: NEJM, NEJM, J Clin Oncol

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Time to start using newer oral anticoagulants for DVT-PE in cancer patients?