ANASTROZOLE VERSUS MEGESTROL-ACETATE IN THE TREATMENT OF POSTMENOPAUSAL WOMEN WITH ADVANCED BREAST-CARCINOMA - RESULTS OF A SURVIVAL UPDATEBASED ON A COMBINED ANALYSIS OF DATA FROM 2 MATURE PHASE-III TRIALS

BACKGROUND, This report presents the results of a survival update base d on the combined data from two studies that compared the efficacy and tolerability of anastrozole (1 or 10 mg once daily), a selective, non steroidal aromatase inhibitor administered orally, and megestrol aceta te (40 mg 4 times daily) in the treatment of postmenopausal women with advanced breast carcinoma whose disease had progressed after treatmen t with tamoxifen. METHODS. Two randomized, parallel-group, multicenter trials were conducted, involving a total of 764 patients. The two tri als were identical in design; both were double blind for anastrozole a nd open label for megestrol acetate. Overview analyses were conducted with the intent of strengthening the interpretation of results from ea ch trial. The median follow-up duration for this survival update was 3 1 months. RESULTS. At the clinical dose of 1 mg daily, anastrozole dem onstrated a statistically significant survival advantage over megestro l acetate, with a hazard ratio of 0.78 (P < 0.025)(0.60 < 97.5% confid ence interval [CI] <1.0). The 1 mg anastrozole group also had a longer median time to death (26.7 months) compared with 22.5 months for the megestrol acetate group. The 10 mg anastrozole group also had a surviv al benefit over the megestrol acetate group, with a hazard ratio of 0. 83 (P = 0.09, not significant)(0.64 < 97.5% CI < 1.1). Higher 2-year s urvival rates were observed for both anastrozole treatment groups than for the megestrol acetate group (56.1%, 54.6%, and 46.3% for the grou ps given 1 mg anastrozole, 10 mg anastrozole, and megestrol acetate, r espectively). CONCLUSIONS. This combined analysis of two trials of pos tmenopausal patients with advanced breast carcinoma has clearly demons trated that, after disease progression with tamoxifen, treatment with anastrozole 1 mg once daily results in a statistically and clinically significant advantage over a standard treatment, megestrol acetate. Th is important benefit, in addition to the good tolerability profile of anastrozole, supports the use of this drug as a valuable new treatment option for this patient population. (C) 1998 American Cancer Society.