Apixaban Noninferior To Dalteparin For Preventing Embolism In Cancer Patients

Among cancer patients with venous thromboembolism, oral therapy with apixaban is just as effective for preventing a subsequent clot as dalteparin, according to a new open-label noninferiority study of 1,155 volunteers.

The rates were actually a bit better with apixaban: 5.6% developed a recurrent venous thromboembolism vs 7.9% of the patients in the dalteparin group, a reduction of 37%.

Major bleeding rates were similar in the two cohorts: 3.8% with apixaban and 4.0% with dalteparin (P=0.60).

The test, known as Caravaggio, was funded by Bristol-Myers Squibb, which supplied the apixaban, and Pfizer, which provided the dalteparin.

The results were released online by the New England Journal of Medicine and during an online presentation Sunday as part of the American College of Cardiology and World Congress of Cardiology's virtual annual meeting.

The study "provides the latest wave of evidence regarding the efficacy and safety of apixaban for the treatment of venous thromboembolism in patients with cancer," said Dr. Agnes Lee of the University of British Columbia in a Journal editorial.

Up to 20% of cancer patients may experience a venous thromboembolism and most guidelines recommend treatment with a low-molecular-weight heparin-class drug for treatment. But there is growing evidence that direct oral anticoagulants may work as well.

The new study was done at 119 centers in Europe, Israel and the United States.

Most had advanced cancer. Patients with acute leukemia, a primary brain tumor, known intracerebral metastases or basal-cell or squamous-cell carcinoma of the skin were excluded.

All had a newly-diagnosed symptomatic or incidental acute proximal deep-vein thrombosis or pulmonary embolism.

They were randomly assigned to 10 mg of apixaban twice day for 7 days (a dose then reduced to 5 mg twice daily for the remainder of their 6-month treatment) or 200 IU/kg once daily of dalteparin (which was reduced to 150 IU/kg daily after one month).

The rates of major gastrointestinal bleeding were 1.9% with apixaban and 1.7% with dalteparin. Major non-gastrointestinal bleeding occurred in 1.9% of apixaban recipients and 2.2% of the patients on dalteparin.

The rates of clinically relevant nonmajor bleeding were 9.0% with apixaban and 6.0% with dalteparin, but the difference was not statistically significant.

The rates of death from any cause by day 210 were comparable in the two groups, 23.4% with apixaban and 26.4% with dalteparin, and more than 85% were related to cancer.

Taken together, "the evidence from these trials makes a compelling case for adding apixaban as another anticoagulant option for the treatment of venous thromboembolism in patients with cancer," said Dr. Lee. "But given the heterogeneity of available trials, it is inappropriate to conclude that one direct oral anticoagulant is better than another without a head-to-head comparison."

The chief author of the study, Dr. Giancarlo Agnelli of the University of Perugia in Italy, did not respond to emailed questions.

—Gene Emery

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