Apixaban noninferior to dalteparin for cancer-related VTE treatment
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Treatment of venous thromboembolism with oral apixaban was noninferior to subcutaneous dalteparin, without increasing major bleeding risk, according to results from the CARAVAGGIO trial presented at the virtual American College of Cardiology Scientific Session.
“The findings of CARAVAGGIO expand the proportion of patients with cancer-associated thrombosis who are eligible for the treatment with the oral direct anticoagulants, including patients with gastrointestinal cancer,” Giancarlo Agnelli, MD, professor of internal medicine and chairman of the postgraduate program in emergency medicine at University of Perugia, Italy, said during the presentation.
CARAVAGGIO enrolled 1,155 patients with cancer and newly diagnosed incidental or symptomatic proximal lower-limb deep vein thrombosis or pulmonary embolism. Patients were assigned to receive 6 months of apixaban (n = 576; mean age, 67 years; 51% men) or dalteparin (Fragmin, Pfizer; n = 579; mean age, 67 years; 48% men). For the first 7 days, the apixaban dose was 10 mg twice daily, then decreased to 5 mg. Dalteparin was administered at 200 IU/kg of body weight once daily for the first month, then reduced to 150 IU/kg once per day. Median treatment duration was 178 days in the apixaban group and 175 days in the dalteparin group.
VTE, bleeding results
The primary outcome — recurrent VTE during the 6-month period — occurred in 5.6% of patients assigned apixaban vs. 7.9% assigned dalteparin (HR = 0.63; 95% CI, 0.37-1.07; P for noninferiority < .001; P for superiority = .09).
“This corresponds to a 37% risk reduction,” Agnelli, who is also director of the division of internal vascular emergency medicine and stroke unit at the University Hospital in Perugia, said during virtual presentation of the results.
The principal safety outcome — major bleeding through 72 hours after the last dose was administered — was observed in 3.8% of the apixaban group vs. 4% of the dalteparin group (HR = 0.82; 95% CI, 0.4-1.69).
In other results, the cumulative incidence of major bleeding or recurrent VTE occurred in 8.9% of patients assigned apixaban vs. 11.4% of those assigned dalteparin (HR = 0.7; 95% CI, 0.45-1.07).
Researchers observed clinically relevant nonmajor bleeding in 9% of the apixaban group vs. 6% of the dalteparin group (HR = 1.42; 95% CI, 0.88-2.3), and major or clinically relevant nonmajor bleeding in 12.2% vs. 9.7%, respectively (HR = 1.16; 95% CI, 0.77-1.75.).
By day 210, all-cause death occurred in 23.4% of patients assigned apixaban and 26.4% of those assigned dalteparin. Most deaths were related to cancer, Agnelli said.
In subgroup analyses, researchers observed a significant interaction between age subgroups and treatment for recurrent VTE.
“I do believe that the data on apixaban from the CARAVAGGIO study actually extend the number of patients [who] could receive the oral agent, and ... this includes patients with GI cancers,” Agnelli said. “Of course, we are building on something that is already known, but I think it’s some additional information that is important for completing the story.”
The results were published simultaneously in The New England Journal of Medicine.
Changing landscape
During a discussion of the trial, panelist Bonnie Ky, MD, MSCE, associate professor of medicine and epidemiology at the University of Pennsylvania Perelman School of Medicine and editor-in-chief of JACC: CardioOncology, said she was “particularly impressed by the low rate of bleeding, which has been traditionally a concern with [direct oral anticoagulants] as well as the demonstration of noninferiority of apixaban.”
“This study is extremely important because treatment with direct oral anticoagulants without a previous lead-in course of heparin has thus far been limited to pilot studies,” panelist Robert M. Carey, MD, MACP, professor of medicine and dean emeritus at University of Virginia School of Medicine in Charlottesville, said during the discussion. “The present study conclusively shows noninferiority of a direct oral anticoagulant (apixaban) to low molecular weight heparin.”
In a related editorial, Agnes Y.Y. Lee, MD, MSc, FRCP(C), medical director of the thrombosis program and professor of medicine at University of British Columbia in Vancouver, Canada, wrote: “Since the landscape of cancer therapy and survival is rapidly changing, anticoagulant therapy in patients with cancer needs to keep pace. Direct oral anticoagulants mark a welcome step forward in providing effective and safe therapeutic choices for patients with cancer and venous thromboembolism.” – by Darlene Dobkowski
References:
Agnelli G, et al. Late-Breaking Clinical Trials III. Presented at: American College of Cardiology Scientific Session; March 28-30, 2020 (virtual meeting).
Agnelli G, et al. N Engl J Med. 2020;doi:10.1056/NEJMoa1915103.
Lee AYY. N Engl J Med. 2020;doi:10.1056/NEJMe2004220.
Disclosures: The trial was funded by the Bristol-Myers Squibb-Pfizer Alliance. Agnelli reports he received personal fees from Bayer Healthcare and Pfizer and other support from Daiichi Sankyo. Lee reports she received personal fees from Bayer, Bristol-Myers Squibb, Eli Lilly, LEO Pharma, Pfizer and Quercegen Pharmaceuticals, grants from Bristol-Myers Squibb and non-financial support from Bayer and Bristol-Myers Squibb. Ky reports she received consultant fees/honoraria from Bristol-Myers Squibb, Springer Nature and UpToDate, investigator-initiated research support from Roche Diagnostics, research support from the American Heart Association and NIH and is the editor-in-chief of JACC: CardioOncology. Carey reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.