medwireNews: The direct oral anticoagulant apixaban is noninferior to subcutaneous dalteparin for the treatment of cancer-related venous thromboembolism (VTE), without an associated increase in the risk for major bleeding, suggest phase 3 trial results.
The Caravaggio trial included individuals with cancer and a new diagnosis of symptomatic or incidental proximal lower-limb deep vein thrombosis or pulmonary embolism. Participants were randomly assigned to receive 6 months of treatment with either apixaban at a dose of 10 mg twice daily for a week with a reduction to 5 mg twice daily thereafter, or dalteparin 200 IU/kg per day for a month, after which the daily dose was reduced to 150 IU/kg.
As reported in The New England Journal of Medicine, the primary endpoint of recurrent VTE occurred in 5.6% of the 576 trial participants who received at least one dose of apixaban and in 7.9% of their 579 counterparts who received one or more doses of the low molecular weight heparin. This equated to a hazard ratio of 0.63 in favor of apixaban and met the prespecified criteria for noninferiority.
Apixaban treatment did not lead to an increase in the incidence of major bleeding, at 3.8% versus 4.0% with dalteparin. Importantly, this was true also for major gastrointestinal bleeding, which the researchers explain can be a concern with the oral agents, with comparable rates of 1.9% and 1.7% in the apixaban and dalteparin groups, respectively.
Giancarlo Agnelli, from the University of Perugia in Italy, and fellow investigators point out, however, that the incidence of clinically relevant nonmajor bleeding was numerically higher with apixaban than dalteparin, at 9.0% versus 6.0%.
“The efficacy of apixaban was consistent with and contributes to evidence of the efficacy of direct oral anticoagulants in the treatment of venous thromboembolism” in people with cancer, write the study authors.
But they caution that “as in the large majority of studies regarding the treatment of venous thromboembolism, the sample size of our trial was powered for the primary outcome (recurrent venous thromboembolism) and was not powered to make definitive conclusions about bleeding.”
Writing in an accompanying editorial, Agnes Lee (University of British Columbia, Vancouver, Canada) notes that the evidence from this and previous studies “makes a compelling case for adding apixaban as another anticoagulant option for the treatment of venous thromboembolism in patients with cancer.”
But she believes “it is inappropriate to conclude that one direct oral anticoagulant is better than another without a head-to-head comparison” in light of the heterogeneity of the trials.
Lee continues: “So how do we choose which anticoagulant to use? Carefully!
“Clinicians need to rely on a detailed clinical history, ascertaining the cancer type, status, and treatment, along with bleeding risk, concomitant medications, and the patient’s experiences and values.”
She acknowledges, however, that “[d]irect oral anticoagulants mark a welcome step forward in providing effective and safe therapeutic choices for patients with cancer and venous thromboembolism.”
The Caravaggio trial results were presented simultaneously at the ACC.20/WCC virtual meeting.
medwireNews is an independent medical news service provided by Springer Healthcare. © 2020 Springer Healthcare part of the Springer Nature Group
N Engl J Med 2020; doi:10.1056/NEJMoa1915103
N Engl J Med 2020; doi:10.1056/NEJMe2004220