From the Guidelines
Apixaban is recommended over placebo for preventing recurrent venous thromboembolism (VTE) in patients with cancer-associated thrombosis, with a significant reduction in VTE risk and a favorable bleeding profile. The standard dose is 2.5 mg twice daily, as shown in the AVERT study 1, which demonstrated a significant reduction in VTE rate (4.2% on apixaban and 10.2% on placebo, hazard ratio [HR] 0.41; 95% CI, 0.26–0.65; p<0.001).
Key Considerations
- The AVERT study 1 and subsequent guidelines 1 support the use of apixaban for VTE prevention in cancer patients, with a focus on its efficacy and safety profile.
- The ADAM VTE trial 1 compared apixaban with dalteparin for VTE treatment in cancer patients, showing a lower risk of recurrent VTE with apixaban (0.7% vs 6.3%, P = 0.03).
- The ESMO clinical practice guideline 1 recommends apixaban as a treatment option for VTE in cancer patients, with a standard dose of 10 mg twice daily for 7 days, followed by 5 mg twice daily for at least 6 months.
Monitoring and Adjustments
- Patients should be monitored for potential side effects, including bleeding, and dose adjustments may be necessary for those with renal impairment, low body weight, or those taking certain interacting medications.
- Treatment duration beyond 6 months should be individualized based on ongoing cancer status, treatment, and risk factors.
- Patients should be educated about potential drug interactions, especially with chemotherapy agents, and the importance of maintaining consistent dosing without abrupt discontinuation.
From the FDA Drug Label
In the AMPLIFY-EXT study, both doses of apixaban were superior to placebo in the primary endpoint of symptomatic, recurrent VTE (nonfatal DVT or nonfatal PE), or all-cause death (Table 14). Table 14: Efficacy Results in the AMPLIFY-EXT Study Apixaban 2. 5 mg bid N=840 Apixaban 5 mg bid N=813 Placebo N=829 Relative Risk (95% CI) Apixaban 2.5 mg bid vs Placebo Apixaban 5 mg bid vs Placebo n Recurrent VTE or all- cause death DVT* PE* All-cause death 32 (3.8) 19 (2.3) 23 (2.7) 22 (2.6) 34 (4.2) 28 (3.4) 25 (3.1) 25 (3.1) 96 (11.6) 72 (8.7) 37 (4.5) 33 (4.0) 0.33 (0.22,0.48) p<0.0001 0.36 (0.25,0.53) p<0. 0001
- Patients with more than one event are counted in multiple rows.
The incidence of recurrent VTE in cancer-associated thrombosis with apixaban versus placebo is not directly addressed in the provided drug labels. However, the AMPLIFY-EXT study compared apixaban to placebo for the extended treatment of DVT and PE, and the results showed that apixaban was superior to placebo in reducing the risk of recurrent VTE.
- Key findings:
- Apixaban 2.5 mg bid: 32 (3.8%) recurrent VTE or all-cause death
- Apixaban 5 mg bid: 34 (4.2%) recurrent VTE or all-cause death
- Placebo: 96 (11.6%) recurrent VTE or all-cause death
- Relative risk:
- Apixaban 2.5 mg bid vs placebo: 0.33 (0.22,0.48)
- Apixaban 5 mg bid vs placebo: 0.36 (0.25,0.53) 2
From the Research
Apixaban versus Placebo in Cancer-Associated Thrombosis
- The provided studies do not directly compare apixaban to placebo in the context of cancer-associated thrombosis and incidence of recurrent VTE 3, 4, 5, 6, 7.
- However, the studies suggest that apixaban is effective in preventing recurrent VTE in patients with cancer-associated thrombosis, with a lower risk of bleeding compared to other anticoagulants such as low molecular weight heparin and warfarin 4, 5, 6, 7.
Efficacy of Apixaban in Preventing Recurrent VTE
- A study published in The New England Journal of Medicine in 2020 found that apixaban was noninferior to dalteparin in preventing recurrent VTE in patients with cancer-associated thrombosis, with a hazard ratio of 0.63 (95% CI, 0.37 to 1.07) 4.
- A systematic review and meta-analysis published in Annals of Medicine and Surgery in 2024 found that apixaban significantly decreased the risk of major bleeding compared to low molecular weight heparin, with a relative risk of 0.67 (95% CI, 0.54 to 0.83) 5.
- A randomized, double-blind, noninferiority trial published in The New England Journal of Medicine in 2025 found that extended anticoagulation with reduced-dose apixaban was noninferior to full-dose apixaban for the prevention of recurrent VTE in patients with active cancer, with an adjusted subhazard ratio of 0.76 (95% CI, 0.41 to 1.41) 7.
Safety of Apixaban in Patients with Cancer-Associated Thrombosis
- The studies suggest that apixaban is associated with a lower risk of bleeding compared to other anticoagulants, with a relative risk of 0.67 (95% CI, 0.54 to 0.83) compared to low molecular weight heparin 5.
- However, the optimal management of bleeding emergencies associated with apixaban therapy is still a concern, and further research is needed to address this issue 6.