Results of the CARAVAGGIO trial found oral apixaban was noninferior to subcutaneous dalteparin for preventing cancer-associated VTE without increasing a patient’s risk for major bleeding.
Giancarlo Agnelli, MD
Results of the CARAVAGGIO trial are shedding new light on the safety and effectiveness of oral apixaban for the treatment of cancer-associated venous thromboembolism (VTE).
Presented at the American College of Cardiology’s Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC), the multinational, randomized, open-label trial found oral apixaban was noninferior to subcutaneous dalteparin for preventing cancer-associated recurrent VTE without increasing a patient’s risk for major bleeding.
In an effort to assess the potential role of apixaban in relation to other direct oral anticoagulants (DOACs) for the prevention of recurrent VTE in patients with cancer, investigators initiated the noninferiority trial with blinded central outcome adjudication comparing the agent against dalteparin—a low-molecular-weight heparin.
A total of 1170 individuals from 119 centers underwent 1:1 randomization, of which 576 and 579 patients were included in intention-to-treat and safety analyses for the apixaban and dalteparin groups, respectively. Patients included in the study were required to have newly diagnosed symptomatic or incidental proximal lower-limb deep-vein thrombosis (DVT) or pulmonary embolism. Cancer types included in the study included all confirmed cancers other than basal-cell or squamous-cell carcinoma of the skin, primary brain tumor, known intracerebral metastases, or acute leukemia.
All patients underwent treatment for a total of 6 months. For the first 7 days, patients were administered apixaban 10 mg twice daily and then 5 mg twice daily after. Dalteparin patients were given a subcutaneous dose of 200 IU per kg of body weight once daily for the first month and a dose of 150 IU per kg daily after.
Of note, investigators allowed for drugs to be withheld in case of a platelet count lower than 50,000 per cubic millimeter or any condition associated with an increased risk of bleeding. Additionally, the protocol could be amended to allow dalteparin dosing adjustments based on country-specific labeling.
The primary outcome of the trial was objectively confirmed recurrent VTE, including proximal DVT of lower limbs, symptomatic DVT, and pulmonary embolism during the 6-month trial period. The principal safety outcome was major bleeding, which was defined as clinically overt bleeding. Trial visits took place at enrollment, 4 weeks, 3 months, 6 months, and 7 months after randomization—additional visits could be scheduled as needed if signs of VTE or bleeding occurred.
Analysis revealed recurrent VTE occurred in 5.6% (n=32) of patients receiving apixaban and 7.9% (n=46) of patients receiving dalteparin (HR, 0.63; 95% CI, 0.37-1.07; P <.001 for noninferiority; P=.09 for superiority). Major bleeding was observed in 3.8% (n=22) of patients receiving apixaban and 4.0% (n=23) of those receiving dalteparin (HR, 0.82; 95% CI, 0.40-1.69; P=.60).
Investigators noted major gastrointestinal bleeding took place in 1.9% (n=11) of the apixaban group and in 1.7% (n=10) in the dalteparin group while major nongastrointestinal bleeding occurred in 1.9% (n=11) of the apixaban group and 2.2% (n=13) of the dalteparin group. No fatal bleeding episodes occurred in the apixaban group but occurred in 2 patients receiving dalteparin.
Overall, the cumulative incidence of recurrent VTE or major bleeding was 8.9% for apixaban and 11.4% for dalteparin (HR, 0.70; 95% CI, 0.45-1.07). Results indicated clinically relevant nonmajor bleeding occurred in 9.0% (n=52) of apixaban patients and 6.0% (n=35) of dalteparin patients.
Investigators suggest the apparent results of the analysis indicate oral apixaban’s noninferiority to subcutaneous dalteparin for treatment of cancer-associate VTE without causing an increased risk of major bleeding—an adverse event associated with other agents in the class.
This study, “Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer,” was presented at ACC.20/WCC.