Results from a trial presented at the 2018 ASH Annual Meeting add more support for the use of direct oral anticoagulants (DOACs) in patients with cancer-associated venous thromboembolism (VTE). The newer agent was associated with lower risk of VTE recurrence, compared with the low-molecular weight heparin (LMWH) dalteparin, as well as a higher patient-reported quality of life.
“LMWH is the guideline-endorsed treatment of patients with cancer-associated VTE,” Robert D. McBane, MD, from the Mayo Clinic in Rochester, Minnesota, said during his presentation of results from the randomized ADAM VTE trial.
In this trial, researchers compared the efficacy of the DOAC apixaban with parenteral dalteparin in reducing bleeding, improving quality of life, and lowering VTE recurrence in patients with active cancer-associated VTE.
A total of 300 patients with cancer-associated acute VTE were assigned to six months of treatment with either:
- apixaban 10 mg twice-daily for 7 days, followed by 5 mg twice-daily (n=145)
- dalteparin 200 IU/kg for 1 month, followed by 150 IU/kg once-daily (n=142)
The primary endpoint of the trial was major bleeding events; secondary endpoints included recurrence of VTE and a composite of major plus clinically relevant non-major bleeding.
In the cohort, 65.5 percent of patients presented with metastatic disease at baseline, and 74 percent of patients were receiving concurrent systemic cancer therapy. The four most prevalent types of cancer were breast, colorectal, lung, and pancreatic.
During the study, similar proportions of patients in the apixaban and dalteparin arms experienced major bleeding (0% vs. 2.1%, respectively; p=0.1).
Rates of the secondary safety and efficacy endpoints are presented in the TABLE. A significantly lower proportion of patients in the apixaban group experienced recurrent VTE, compared with the dalteparin group, for a risk reduction of –10.7 percentage points with apixaban treatment. These included similar incidence of pulmonary embolism (n=4 in each group) but a higher incidence of lower- and upper-extremity deep vein thrombosis in the placebo group (0 in the apixaban group vs. 8 and 5 in the placebo group).
Six-month mortality rates also were similar between the two treatment arms: 15.9 percent with apixaban versus 10.6 percent for dalteparin (HR=1.36; 95% CI 0.79-2.35; p value not provided).
Patients appeared to prefer the oral administration of apixaban, compared with subcutaneous injections of dalteparin. According to surveys conducted each month during follow-up, the lower treatment burden of apixaban was associated with better quality of life, and patients reported a lower concern for excess bruising, irritation, and stress, and higher overall satisfaction with therapy (p<0.05).
Limitations of the study include the relatively small number of enrolled patients, as well as the reliance on self-reported questionnaire data to evaluate secondary outcomes.
The authors report no relevant financial relationships.
McBane RD, Wysokinski WE, Le-Rademacher J, et al. Apixaban, dalteparin, in active cancer associated venous thromboembolism, the ADAM VTE trial. Abstract #421. Presented at the 2018 ASH Annual Meeting, December 2, 2018; San Diego, CA.
TABLE. Secondary Clinical Outcomes During Treatment
(95% CI; p value)
|Major plus clinically non-relevant major bleeding||9 (6.2%)||9 (6.3%)||0.9 (0.41-1.94; 0.882)|
|Recurrent venous thromboembolism||5 (3.4%)||20 (14.1%)||0.21 (0.09-0.47; p=0.0182)|