A randomized phase II trial of apixaban for the prevention of thromboembolism in patients with metastatic cancer

Background: Cancer patients receiving chemotherapy are at increased risk for thrombosis. Apixaban, a factor Xa inhibitor, is oral and does not require laboratory monitoring. Objectives:  A pilot study was conducted to evaluate whether apixaban would be well tolerated and acceptable in cancer patients receiving chemotherapy. Patients/Methods:  Subjects receiving either first-line or second-line chemotherapy for advanced or metastatic lung, breast, gastrointestinal, bladder, ovarian or prostate cancers, cancer of unknown origin, myeloma or selected lymphomas were randomized to 5mg, 10mg or 20mg once daily of apixaban or placebo in a double-blind manner for 12 weeks. Use of the study drug began within 4 weeks of the start of chemotherapy. The primary outcome was either major bleeding or clinically relevant non-major (CRNM) bleeding. Secondary outcomes included venous thromboembolism (VTE) and grade III or higher adverse events related to the study drug. Thirty-two patients received 5mg, 30 patients 10mg, 33 patients 20mg, and 30 patients placebo. In these groups, there were 0, 0, 2 and 1 major bleeds, respectively. The corresponding data for CRNM bleeds were 1, 1, 2, and 0. The rate of major bleeding in the 93 apixaban patients was 2.2% (95% confidence interval 0.26-7.5%). There were no fatal bleeds. Three placebo patients had symptomatic VTE. Conclusions:  Apixaban was well tolerated in our study population. These results support further study of apixaban in phase III trials to prevent VTE in cancer patients receiving chemotherapy.