ALBERT

Description: Background The risk of venous thromboembolism (VTE) is increased in patients with active cancer, contributing substantially to morbidity and mortality. Further, the VTE risk is even higher for patients with metastatic cancer than those with local disease. In the AVERT trial, apixaban thromboprophylaxis resulted in a significantly lower rate of venous thromboembolism and an increased rate of major bleeding than did placebo among intermediate-to-high-risk ambulatory patients with cancer who were starting chemotherapy. In this prespecified subgroup analysis of AVERT, we evaluated the efficacy and safety of apixaban thromboprophylaxis in patients with and without metastatic disease. Methods Eligible participants were randomized to receive either apixaban (2.5mg twice daily) or placebo (identical tablets twice daily) up to five days before the first administration of chemotherapy. The first dose of apixaban or placebo was given within 24 hours of the first chemotherapy administration, with the treatment period lasting 180 days. Patients were followed for up to 210 days or death, regardless of the duration of the treatment period. The primary efficacy outcome was objectively documented major VTE (proximal deep-vein thrombosis or pulmonary embolism) occurring within 180 days (±3 days ) following randomization. The primary safety outcome was major bleeding, as defined by the International Society on Thrombosis and Hemostasis criteria. For this subgroup analysis, the efficacy and safety of apixaban thromboprophylaxis was evaluated in patients with and without documented metastatic disease. The primary efficacy analysis was performed in the modified intention-to-treat population, which included all the patients who had undergone randomization and received at least one dose of apixaban or placebo on or before day 180 (±3 days). The primary safety analysis was performed in the on-treatment population, in which events were only counted if they occurred during the period the subject was taking the study drug (or up to two days post discontinuation). Results A total of 574 patients underwent randomization, with 563 patients included in the original primary efficacy and safety analysis. A total of 366 patients could be stratified according to the presence or absence of metastatic disease, with 138 having metastatic disease and 228 having non-metastatic disease. The baseline characteristics were balanced between the treatment and placebo arms in both the metastatic and non-metastatic groups (Table 1). In patients with metastatic disease, VTE occurred in 6 of out of 73 in the treatment group and 10 out of 65 in the placebo group [HR 0.55 95% CI 0.32-0.97, p=0.0381]. In patients with metastatic disease, major bleeding occurred in 3 out of 73 in the treatment group and 2 out of 65 in the placebo group [HR 1.47 95% CI 0.29-6.76, p= 0.69]. In patients with non-metastatic disease, VTE occurred in 4 out of 107 in the treatment group, and 14 out of 121 in the placebo group [HR 0.35 95% CI 0.20-0.61, p= 0.0002]. In patients with non-metastatic disease, major bleeding occurred in 1 out of 107 in the treatment group and 1 out of 121 in the placebo group [HR 1.20 95%CI 0.11-13.38, p=0.881]. Conclusions: In patients with and without metastatic disease, apixaban thromboprophylaxis was associated with a significantly lower rate of VTE compared to placebo, with no significant difference in the rate of major bleeding. This subgroup analysis thus suggests that apixaban thromboprophylaxis is both safe and effective in cancer patients regardless of the presence of absence of metastatic disease. Table 1. Disclosures Wells: Daiichi Sankyo: Honoraria; BMS/Pfizer: Honoraria, Research Funding; Bayer: Honoraria; Sanofi: Honoraria. Carrier:Leo Pharma: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Bayer: Honoraria; Servier: Honoraria. OffLabel Disclosure: Apixaban can be used as postoperative prophylaxis of DVT/PE and for treatment of DVT/PE. We looked at using apixaban 2.5mg BID for the primary thromboprophylaxis of ambulatory cancer patients initiating chemotherapy, at intermediate-high risk of venous thromboembolism.