Phase III randomized trial of second-line ixabepilone versus paclitaxel or doxorubicin in women with advanced endometrial cancer

OBJECTIVE: The purpose of this multicenter, open label, randomized phase III study was to determine whether ixabepilone resulted in improved overall survival (OS) compared with commonly used single-agent chemotherapy (doxorubicin or paclitaxel) in women with locally advanced, recurrent, or metastatic endometrial cancer with at least one failed prior platinum-based chemotherapeutic regimen. METHODS: Patients were randomized 1:1 to ixabepilone (40mg/m(2)), or either paclitaxel (175mg/m(2)) or doxorubicin (60mg/m(2)), every 21days. Patients that had previously received an anthracycline were randomized to ixabepilone or paclitaxel; all other patients were randomized to ixabepilone or doxorubicin. An interim analysis of futility for OS was planned. RESULTS: At the time of database lock, 496 patients were randomized to receive ixabepilone (n=248) or control (n=248); nine patients in the control arm were not treated. The interim analysis of futility for OS (219 events) favored the control chemotherapy arm (hazard ratio=1.3 [95% confidence interval: 1.0-1.7], stratified log rank test P=0.0397), indicating that the study would not meet its primary objective. The study was discontinued based on the interim OS results. The frequency of adverse events was comparable between the treatment arms. CONCLUSIONS: The study did not meet its primary objective of improving OS in the ixabepilone arm compared to the control chemotherapy arm. A favorable risk/benefit ratio was not observed for ixabepilone versus control at the time of the interim analysis. The safety results were consistent with the known safety profiles of ixabepilone and control.