Oral apixaban appears to be noninferior to subcutaneous dalteparin, a low-molecular-weight heparin, for the prevention of cancer-associated venous thromboembolism (VTE) and does not increase the risk of major bleeding, according to results published in The New England Journal of Medicine.

A team of investigators conducted a multinational, randomized, investigator-initiated, open-label, noninferiority trial (Caravaggio; ClinicalTrials.gov Identifier: NCT03045406) to determine the noninferiority of apixaban to dalteparin without increasing the risk of major bleeding.

Between April 2017 and June 2019, consecutive adult patients with cancer who had newly diagnosed symptomatic or incidental acute proximal deep-vein thrombosis or pulmonary embolism were randomly assigned (1:1) to receive twice daily oral apixaban (10 mg for 7 days, then 5 mg thereafter) or once daily subcutaneous dalteparin (200 IU/kg of body weight for 1 month, then 150 IU/kg thereafter) for 6 months.

The primary efficacy outcome was objectively confirmed recurrent VTE. The primary safety outcome was major bleeding. All trial outcome events were centrally adjudicated.


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For the modified intention-to-treat analysis, 1155 patients (mean age, 67.2 years) were included; 576 patients were treated with apixaban and 579 patients were treated with dalteparin.

The occurrence of recurrent VTE was similar between the apixaban group and dalteparin group (5.6% vs 7.9% of patients, respectively; hazard ratio [HR], 0.63; 95% CI, 0.37-1.07; P <.001 for noninferiority).

The percentage of patients who experienced major bleeding events was also similar between the 2 treatment groups (3.8% in the apixaban group vs 4.0% in the dalteparin group; HR, 0.82; 95% CI, 0.40-1.69; P =.60).

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The authors noted several limitations of the study including the fact that it was an open-label study to avoid the use parenteral placebo; gastrointestinal bleeding was not a prespecified trial outcome; patients with brain tumors or acute leukemia were not enrolled; and it was underpowered for conclusions on bleeding outcomes.

“The favorable safety profile that we found for apixaban is in agreement with the results of previous randomized trials of this drug with respect to the treatment of venous thromboembolism in the general population,” the investigators wrote. “Taken together, these findings may expand the proportion of patients with both cancer and venous thromboembolism who would be eligible for treatment with apixaban, including patients with gastrointestinal cancer.”

Disclosure: The study was supported by the Bristol-Myers Squibb–Pfizer Alliance. Please see the original reference for a full list of authors’ disclosures.

Reference

Agnelli G, Becattini C, Meyer G, et al. Apixaban for the treatment of venous thromboembolism associated with cancer [published online March 29, 2020]. N Engl J Med. doi: 10.1056/NEJMoa1915103