Apixaban for the treatment of venous thromboembolism in cancer patients

BACKGROUND:

Using data from AMPLIFY, a phase III trial comparing apixaban with conventional anticoagulant treatment in patients with venous thromboembolism (VTE), we performed subgroup analyses to compare the efficacy and safety of these regimens in patients with and without active cancer at baseline. Active cancer was defined as cancer that was diagnosed or treated within the past 6 months.

METHODS:

Patients with symptomatic VTE were randomized to a 6-month course of apixaban (10mg BID for 7 days followed by 5mg BID) or conventional treatment consisting of enoxaparin (1mg/kg BID for at least 5 days) followed by dose-adjusted warfarin (target INR, 2-3). Cancer patients for whom long-term low-molecular-weight heparin (LMWH) was planned were excluded. The primary efficacy outcome was symptomatic VTE or VTE-related death. The intent-to-treat efficacy analysis included all randomized subjects with a non-missing primary endpoint. The primary safety outcome was ISTH-defined major bleeding up to 2 days after stopping study drug in all randomized subjects who received at least one dose of study medication. All outcomes were adjudicated by an independent committee blinded to treatment assignment.

RESULTS:

Of 5395 patients randomized, 169 (3.1%) had active cancer. Baseline characteristics in these patients were similar between the two treatment groups. The median duration of treatment was 167 and 168 days in the apixaban and warfarin groups, respectively. In patients with active cancer at entry, recurrent VTE occurred in 3 of 81 (3.7%) patients in the apixaban group and in 5 of 78 (6.4%) in the warfarin group (relative risk [RR], 0.56; 95% CI, 0.13-2.37); major bleeding occurred in 2 of 87 (2.3%) and 4 of 80 (5.0%) patients, respectively (RR, 0.45; 95% CI, 0.08-2.46). In patients without cancer at entry, recurrent VTE occurred in 56 of 2528 (2.2%) and in 66 of 2557 (2.6%) patients in the apixaban and warfarin group, respectively (RR, 0.86; 95% CI, 0.60-1.22), whereas major bleeding occurred in 13 of 2589 (0.5%) and in 45 of 2609 (1.7%) patients in the apixaban and warfarin group, respectively (RR, 0.29; 95% CI, 0.16-0.54).

CONCLUSION:

Although the number of cancer patients was small, the results in this pre-specified subgroup are consistent with the overall findings and suggest that apixaban is as effective as conventional therapy in VTE patients with active cancer, and is associated with less bleeding. Additional studies are needed to compare the efficacy and safety of apixaban and LMWH for VTE treatment in cancer patients.