SAN DIEGO—Apixaban is as safe as, and more effective than, dalteparin for patients with cancer-associated venous thromboembolism (VTE), according to the ADAM VTE trial.
Patients who received apixaban in this trial had similar rates of major bleeding and clinically relevant non-major bleeding as patients who received dalteparin.
However, the rate of VTE recurrence was significantly lower with apixaban than with dalteparin.
“[A]pixaban was associated with very low bleeding rates and venous thrombosis recurrence rates compared to dalteparin,” said Robert D. McBane, MD, of the Mayo Clinic in Rochester, Minnesota.
Dr. McBane presented these results at the 2018 ASH Annual Meeting (abstract 421*).
ADAM VTE (NCT02585713) included 300 adults (age 18 and older) with active cancer and acute VTE who were randomized to receive apixaban (n=150) or dalteparin (n=150).
The dose and schedule for oral apixaban was 10 mg twice daily for 7 days, followed by 5 mg twice daily for 6 months. Dalteparin was given subcutaneously at 200 IU/kg per day for 1 month, followed by 150 IU/kg daily for 6 months.
One hundred and forty-five patients in the apixaban arm and 142 in the dalteparin arm ultimately received their assigned treatment.
Every month, patients completed an anticoagulation satisfaction survey and bruise survey (a modification of the Duke Anticoagulation Satisfaction Scale). They also underwent lab testing (complete blood count, liver and renal function testing) and were assessed for outcomes, medication reconciliation, drug compliance, and ECOG status on a monthly basis.
Baseline characteristics were similar between the treatment arms. The mean age was 64 in both arms, and roughly half of patients in both arms were female.
Nine percent of patients in the apixaban arm and 11% in the dalteparin arm had hematologic malignancies. Other cancers included colorectal, lung, pancreatic/hepatobiliary, gynecologic, breast, genitourinary, upper gastrointestinal, and brain cancers.
Sixty-five percent of patients in the apixaban arm and 66% in the dalteparin arm had distant metastasis. Seventy-four percent of patients in both arms were receiving chemotherapy while on study.
Patients had the following qualifying thrombotic events:
- Any pulmonary embolism (PE)—55% of patients in the apixaban arm and 51% in the dalteparin arm
- Any deep vein thrombosis (DVT)—48% and 47%, respectively
- PE only—44% and 39%, respectively
- PE with DVT—12% in both arms
- DVT only—37% and 35%, respectively
- Lower extremity DVT—31% and 34%, respectively
- Upper extremity DVT—17% and 14%, respectively
- Cerebral venous thrombosis (VT)—1% and 0%, respectively
- Splanchnic VT—8% and 18%, respectively.
Bleeding, thrombosis, and death
The study’s primary endpoint was major bleeding, which did not occur in any of the apixaban-treated patients. However, major bleeding did occur in two (1.4%) patients in the dalteparin arm (P=0.14).
A secondary endpoint was major bleeding plus clinically relevant nonmajor bleeding. This occurred in nine (6.2%) patients in the apixaban arm and nine (6.3%) in the dalteparin arm (P=0.88).
The researchers also assessed VTE recurrence. One patient in the apixaban arm (0.7%) and nine in the dalteparin arm (6.3%) had VTE recurrence (P=0.03).
The patient in the apixaban arm experienced cerebral VT, and the patients with recurrence in the dalteparin arm had leg (n=4) or arm (n=2) VTE, PE (n=1), or splanchnic VT (n=2).
One patient in each arm (0.7%) had arterial thrombosis.
There was no significant difference in cumulative mortality between the treatment arms (hazard ratio=1.40; P=0.3078).
Satisfaction and discontinuation
Overall, apixaban fared better than dalteparin in the monthly patient satisfaction surveys. At various time points, apixaban-treated patients were significantly less likely to:
- Be concerned about excessive bruising
- Find anticoagulant treatment a burden or difficult to carry out
- Say anticoagulant treatment added stress to their lives, negatively impacted their quality of life, or caused them “a great deal” of worry, irritation, or frustration.
However, apixaban-treated patients were also less likely than dalteparin recipients to have confidence that their drug protected them from VTE recurrence.
Still, the apixaban recipients were more likely than the dalteparin group to report overall satisfaction with their treatment.
In addition, premature treatment discontinuation was more common in the dalteparin group than in the apixaban group—15% and 4%, respectively (P=0.0012).
“Apixaban was well tolerated with superior patient safety satisfaction as well as significantly fewer study drug discontinuations compared to dalteparin,” Dr. McBane said. “I believe that these data support the use of apixaban for the acute treatment of cancer-associated venous thromboembolism.”
This study was funded by BMS/Pfizer Alliance. Dr. McBane declared no other conflicts of interest.
*Data in the presentation differ from the abstract.