Apixaban Thromboprophylaxis in Patients With Cancer
In the Canadian phase III AVERT trial reported in The New England Journal of Medicine, Carrier et al found that the oral factor Xa inhibitor apixaban reduced the risk of venous thromboembolism vs placebo among intermediate- to high-risk ambulatory patients with cancer starting chemotherapy but was associated with a higher rate of major bleeding. As noted by the investigators, it is estimated that patients with solid tumors and a Khorana score of ≥ 2, indicative of intermediate to high risk, have a 9.6% risk of symptomatic thrombosis during the first 6 months of chemotherapy.
Study Details
In the double-blind trial, 574 ambulatory patients who were at intermediate to high risk for venous thromboembolism (Khorana score ≥ 2) and were initiating chemotherapy were recruited from 13 sites in Canada. They were randomly assigned between February 2014 and April 2018 to receive apixaban at 2.5 mg twice daily (n = 291) or placebo (n = 283) for 180 days. The first dose of apixaban or placebo was given within 24 hours after the start of chemotherapy. Outcomes were assessed in the modified intent-to-treat population, consisting of 288 patients in the apixaban group and 275 in the placebo group who received the study drug.
The primary efficacy outcome was objectively documented venous thromboembolism over 180 days. The main safety outcome was major bleeding episodes. Patients were followed for up to 210 days or death, regardless of treatment duration. For the apixaban vs placebo groups, Khorana scores were 2 in 64% vs 67%, 3 in 27% vs 24%, 4 in 9% vs 9%, and 5 in < 1% in both.
Venous Thromboembolism and Major Bleeding
Venous thromboembolism occurred in 12 (4.2%) of 288 patients (4.2%) in the apixaban group vs 28 (10.2%) of 275 patients in the placebo group (hazard ratio [HR] = 0.41, P < .001), including deep-vein thrombosis in 2.4% vs 4.4% and pulmonary embolism in 1.7% vs 5.8%.
Overall, major bleeding occurred in 10 patients (3.5%) in the apixaban group vs 5 patients (1.8%) in the placebo group (HR = 2.00, P = .046). During the treatment period, major bleeding occurred in 6 patients (2.1%) in the apixaban group vs 3 patients (1.1%) in the placebo group (HR = 1.89, 95% confidence interval = 0.39–9.24).
The investigators concluded, “Apixaban therapy resulted in a significantly lower rate of venous thromboembolism than did placebo among intermediate- to high-risk ambulatory patients with cancer who were starting chemotherapy. The rate of major bleeding episodes was higher with apixaban than with placebo.”
Disclosure: The study was funded by the Canadian Institutes of Health Research and Bristol-Myers Squibb–Pfizer Alliance. The study authors’ full disclosures can be found at nejm.org.
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