The CARAVAGGIO findings expand the range of patients with cancer-associated thrombosis who are eligible for DOAC therapy to include those with GI cancer
Twice-daily apixaban was noninferior to subcutaneous dalteparin in the prevention of recurrent venous thromboembolism (VTE) in patients with cancer.
Data from the randomized open-label phase III CARAVAGGIO trial demonstrated that the primary efficacy outcome, recurrent proximal deep vein thrombosis (DVT)/pulmonary embolism (PE), occurred in 5.6% of patients randomized to apixaban compared with 7.9% of those assigned to dalteparin over 6 months of follow-up (P for superiority = 0.08, P for noninferiority < 0.001), with no excessive risk of bleeding, including gastrointestinal (GI) bleeding, in the apixaban arm, announced Giancarlo Agnelli, MD, from the University of Perugia, Italy.
“The findings of the CARAVAGGIO expand the proportion of patients with cancer-associated thrombosis who are eligible for the treatment with the oral direct anticoagulants, including patients with GI cancer,” he said. “This is the only trial in cancer-associated thrombosis where a direct-acting oral anticoagulant is not associated with increased GI bleeding, in spite of the inclusion of a substantial proportion of GI cancers.”
Major guidelines recommend the consideration of edoxaban and rivaroxaban for the treatment of VTE in patients with cancer, but the clinical benefit of these oral agents is limited by the high risk of bleeding, mainly at GI sites, associated with their use.
The aim of CARAVAGGIO—the largest study to evaluate the treatment of VTE in cancer—was to assess whether the direct oral anticoagulant apixaban is noninferior to subcutaneous dalteparin for preventing a recurrent VTE in patients with cancer and to evaluate the risk of bleeding.
The multicenter study enrolled 1,170 patients who had symptomatic or incidental acute proximal DVT or PE and any type of cancer (active or recent history) other than basal cell or squamous cell carcinoma of the skin, primary brain tumor or known cerebral metastases, and acute leukemia. They were randomly assigned to oral apixaban (10 mg twice daily for first 7 days followed by 5 mg twice daily) or subcutaneous dalteparin (200 IU/kg of body weight once daily for the first month, followed by 150 IU/kg once daily). Treatment duration was 6 months.
Mean age of patients was 67.2. Fifty-five percent had PE with or without DVT, and 45% had an isolated DVT. Most patients (80.3%) had symptomatic DVT or PE whereas 20% had incidental VTE. Some 97% in both treatment arms had an active cancer at the time of enrollment; 94.3% of patients in the apixaban arm and 91.0% in the dalteparin arm had a solid tumor, of which 32.6% and 32.3%, respectively, were located in the GI tract, including pancreatic and hepatobiliary cancer.
Occurrence of secondary efficacy outcomes were as follows:
- Recurrent DVT: 2.3% of the apixaban arm vs 2.6% of the dalteparin arm
- Recurrent PE: 3.3% of the apixaban arm compared with 5.5% of the dalteparin arm
- Fatal PE: 0.7% of the apixaban group compared with 0.5% of the dalteparin group.
The primary safety outcome, bleeding as defined by the European Medicines Agency, occurred in 3.8% of the apixaban group compared with 4.0% of the dalteparin group (P = 0.60). Rates of major GI bleeding were 1.9% in the apixaban arm vs 1.7% in the dalteparin arm.
There was a numerical excess in clinically relevant nonmajor bleeding events in the apixaban arm vs the dalteparin arm of 9.0% vs. 6.0%, respectively, corresponding to a 42% relative increase in the apixaban arm. “The sites of bleeding in clinically relevant nonmajor bleeding were essentially the genitourinary tract and upper respiratory tract, so again, there was no increase in GI bleeding even when clinically relevant nonmajor bleeding was considered,” said Dr. Agnelli.
The proportion of patients who were free of recurrent VTE, major bleeding events, and death during the study period was 73.3% in the apixaban arm and 68.6% in the dalteparin arm.
This study was published simultaneously online in the New England Journal of Medicine at the time of presentation. The trial was an investigator-initiated study supported by the BMS-Pfizer Alliance. Giancarlo Agnelli, MD, reported nothing to disclose.