A Phase III trial comparing anastrozole (1 and 10 milligrams), a potent and selective aromatase inhibitor, with megestrol acetate in postmenopausal women with advanced breast carcinoma

BACKGROUND. Anastrozole is a new oral aromatase inhibitor with highly potent and selective activity for the aromatase enzyme. In a Phase III trial, the efficacy and tolerability of anastrozole, given in doses in 1 and 10 mg orally once daily, and megestrol acetate, given in does of 40 mg orally 4 times daily, were compared in 386 postmenopausal women with advanced breast carcinoma who progressed after tamoxifen therapy. METHODS. The trial was randomized, double blind for anastrozole, open label to megestrol acetate, parallel group, and multicenter. Patients were randomly assigned to receive anastrozole, 1 mg (n = 128); anastrozole, 10 mg (n = 130); or megestrol acetate (n = 128). The primary efficacy measures were time to progression and tumor response; secondary measures were time to treatment failure duration of response, quality of life, and time to death. RESULTS. With a median duration of follow-up of 6 months, there was no statistical evidence of a difference between either 1 or 10 mg doses of anastrozole and megestrol acetate for any efficacy endpoint. According to rigid response criteria 10%, 6%, and 6% of patients in the anastrozole 1 mg, anastrozole 10 mg, and megestrol acetate groups, respectively, had an objective response (complete response or partial response) and 27%, 24%, and 30% of patients in the respective groups had stable disease for a duration of 24 weeks or longer. Quality-of-life assessments revealed that anastrozole in a 1-mg dose was associated with better physical scores and anastrozole in a 10-mg dose with better psychologic scores than megestrol acetate. Both anastrozole and megestrol acetate were generally well tolerated. Among anticipated adverse events, gastrointestinal disturbance was more common among patients in the anastrozole groups, whereas weight gain occurred more frequently among patients in the megestrol acetate groups. Weight increases of 5% or more and 10% or more were more common among megestrol acetate-treated patients; moreover, patients in this group continued to gain weight over time. CONCLUSIONS. Anastrozole, given in doses of 1 and 10 mg once daily, represents a well tolerated and effective therapeutic option for the treatment of postmenopausal women with advanced breast carcinoma who progress after tamoxifen treatment.