Phase III, multicenter, double-blind, randomized study of letrozole, an aromatase inhibitor, for advanced breast cancer versus megestrol acetate

Purpose: To compare two doses of letrozole (0.5 mg and 2.5 mg every day) an d megestrol acetate (40 mg qid) as endocrine therapy in postmenopausal wome n with advanced breast cancer previously treated with antiestrogens. Patient and Methods: This double-blind, randomized, multicenter, multinatio nal study enrolled 602 patients, all of whom were included in the primary a nalysis in the protocol. Patients had advanced or metastatic breast cancer with evidence of disease progression while receiving continuous adjuvant an tiestrogen therapy, held experienced relapse within 12 months of stopping a djuvant antiestrogen therapy given for at least 6 months, or had experience d disease progression while receiving antiestrogen therapy for advanced dis ease. Tumors were required to be estrogen receptor and/or progesterone rece ptor-positive or of unknown status. Confirmed objective response rate was t he primary efficacy variable. Karnofsky Performance Status and European Org anization for Research and Treatment of Cancer quality-of-life assessments were collected for 1 year. Results: There were no statistically significant differences among the thre e treatment groups for overall objective tumor response. Patients treated w ith letrozole 0.5 mg had improvements in disease progression (P = .044) and a decreased risk of treatment failure (P = .018), compared with patients t reated with megestrol acetate. Letrozole 0.5 mg showed a trend (P = .053) f or survival benefit when compared with megestrol acetate. Megestrol acetate was more likely to produce weight gain, dyspnea, and vaginal bleeding, and the letrozole groups were more likely to experience headache, hair thinnin g, and diarrhea. Conclusion: Given a favorable tolerability profile, once-daily dosing, and evidence of clinically relevant benefit, letrozole is equivalent to megestr ol acetate and should be considered for use as an alternative treatment of advanced breast cancer in postmenopausal women after treatment failure with antiestrogens. (C) 2001 by American Society of Clinical Oncology.