ANASTROZOLE, A POTENT AND SELECTIVE AROMATASE INHIBITOR, VERSUS MEGESTROL-ACETATE IN POSTMENOPAUSAL WOMEN WITH ADVANCED BREAST-CANCER - RESULTS OF OVERVIEW ANALYSIS OF 2 PHASE-III TRIALS

Purpose: To compare the efficacy and tolerability of anastrozole (1 an d 10 mg once daily), a selective, ems, nonsteroidal aromatase inhibito r, and megestrol acetate (40 mg four times daily), in postmenopausal w omen who progressed following tamoxifen treatment. Patients and Method s: Two randomized, double-blind for anastrozole, open-label for megest rol acetate, parallel-group, multicenter trials were conducted in 764 patients. Because both trials were identical in design, an analysis of the combined results was performed to strengthen interpretation of re sults from each trial. Results: The median follow-up duration was appr oximately 6 months. The estimated progression hazards ratios were 0.97 (97.5% confidence interval [Cl], 0.75 to 1.24) for anastrozole 1 mg v ersus megestrol acetate and 0.92 (97.5% Cl, 0.71 to 1.19) for anastroz ole 10 mg versus megestrol acetate. The overall median rime to progres sion was approximately 21 weeks. Approximately one third of patient in each group benefited from treatment. Twenty-seven patients (10.3%) in the anastrozole 1-mg group, 22 (8.9%) in the anastrozole 10-mg group, and 20 (7.9%) in the megestrol acetate group had a complete or partia l response, and 66 (25.1%), 56 (22.6%), and 66 (26.1%) patients, respe ctively, had stable disease for greater than or equal to 24 weeks, For all end points, individual trial results were similar to the results of the combined analysis. Anastrozole and megestrol acetate were well tolerated. Gastrointestinal disturbance was more common among patients in the anastrozole groups than the megestrol acetate group; the diffe rence between the anastrozole 10 mg and megestrol acetate groups was s ignificant (P = .005). Significantly fewer patients in the anastrozole 1-mg (P < .0001) and 10-mg (P < .002) groups had weight gain than in the megestrol acetate group, More than 30% of megestrol acetate-treate d patients had weight gain greater than or equal to 5%, and 10% of pat ients held weight gain greater than or equal to 10%. Patients who rece ived megestrol acetate continued to gain weight over time. Conclusion: Anastrozole, 1 and 10 mg once daily, is well tolerated and as effecti ve as megestrol acetate in the treatment of postmenopausal women with advanced breast cancer who progressed following tamoxifen treatment. M oreover, anastrozole therapy avoids the weight gain associated with me gestrol acetate treatment.