Results from a trial presented at the 2018 ASH Annual Meeting add more support for the use of direct oral anticoagulants in patients with cancer-associated venous thromboembolism (VTE). Apixaban was associated with a lower risk of VTE recurrence compared with the low-molecular-weight heparin (LMWH) dalteparin, as well as a higher patient-reported quality of life.
“One in five cancer survivors will develop VTE, and managing these patients requires a balance between anticoagulation failures (which can be as high as 16% at 6 months) and major bleeding on anticoagulants (which can be as high as 6% at 6 months),” lead author Robert D. McBane, MD, from the Mayo Clinic in Rochester, Minnesota, said during his presentation of results from the randomized ADAM VTE trial.
“LMWH is the guideline-endorsed treatment of patients with cancer-associated VTE,” he added, but in this trial focused on safety, the investigators hypothesized that treatment with apixaban would significantly lower the rates of major bleeding compared with dalteparin in patients with active cancer and confirmed acute deep vein thrombosis (DVT) or pulmonary embolism (PE).
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 (including fatal bleeding and intracranial hemorrhage); secondary endpoints included recurrence of VTE and a composite of major plus clinically relevant non-major bleeding. Participants also completed monthly questionnaires to measure satisfaction with the anticoagulation regimen.
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. Dr. McBane noted that only four percent of participants had an upper gastrointestinal malignancy, although this was not by design or exclusion criteria.
At the study initiation, investigators assumed a six-month major bleeding rate of 6 percent in the dalteparin group and 1.4 percent in the apixaban group. However, “major bleeding was quite a bit lower in both arms than we expected,” Dr. McBane reported. There were no major bleeding events in the apixaban arm, compared with two (1.4%) in the dalteparin group (p=0.14).
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. The recurrent VTE in the apixaban group was a cerebral VTE; while there were four lower-extremity DVTs, two upper-extremity DVTs, one PE, and one splanchnic VTE in the dalteparin group.
Six-month mortality rates also were similar between the two treatment arms (hazard ratio [HR] = 1.40; 95% CI 0.82-2.43; p=0.31).
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 the therapy (p<0.05). Dr. McBane also noted that premature discontinuation was lower in the apixaban arm than the LMWH group (4% vs. 15%; p=0.0012).
Limitations of the study include the relatively small number of enrolled patients, its open-label design, 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.