Phase III double-blind trial of arzoxifene compared with tamoxifen for locally advanced or metastatic breast cancer.

Purpose: To compare the efficacy of arzoxifene with tamoxifen for the treatment of locally advanced or metastatic breast cancer.

Patients And Methods: Women with estrogen- or progesterone-receptor-positive breast cancer who had not received prior systemic therapy, or who had relapsed more than 12 months after stopping adjuvant hormonal therapy, were randomly assigned to receive 20 mg arzoxifene or 20 mg tamoxifen daily. Each treatment arm was to have 240 patients enrolled. The primary end point was progression-free survival. Secondary end points included other measures of tumor response, overall survival, and safety.

Results: Enrollment was stopped when a planned interim analysis of the first 200 patients suggested arzoxifene to be significantly inferior to tamoxifen. The median progression-free survival for the 352 patients who had been randomly assigned when enrollment was stopped was 4.0 months (95% CI, 3.4 to 5.6 months) for the arzoxifene group and 7.5 months (95% CI, 5.9 to 8.8 months) for the tamoxifen group. On-study progression-free survival (P = .011) and time to treatment failure (P = .029) also favored tamoxifen. Overall tumor response rate and median response duration were comparable between the groups. Adverse events were similar between the treatments, except for nausea (more frequent with arzoxifene) and vaginal discharge (more frequent with tamoxifen).

Conclusion: Tamoxifen produced significantly longer progression-free survival and time to treatment failure compared with arzoxifene in the treatment of locally advanced and metastatic breast cancer. There were no significant differences between tumor response rate, clinical benefit rate, or median response duration.