LETROZOLE, A NEW ORAL AROMATASE INHIBITOR FOR ADVANCED BREAST-CANCER - DOUBLE-BLIND RANDOMIZED TRIAL SHOWING A DOSE-EFFECT AND IMPROVED EFFICACY AND TOLERABILITY COMPARED WITH MEGESTROL-ACETATE

Purpose: to compare two doses of letrozole and megestrol acetate (MA) as second-line therapy in postmenopausal women with advanced breast ca ncer previously treated with antiestrogens. Patients and Methods: Five hundred fifty-one patients with locally advanced, locoregionally recu rrent or metastatic breast cancer were randomly assigned to receive le trozole 2.5 mg (n = 174), letrozole 0.5 mg (n = 188), or MA 160 mg (n = 189) once daily in a double-blind, multicenter trial. Data were anal yzed for tumor response and safety variables vp to 33 months of follow -up evaluation and for survival vp to 45 months. Results: Letrozole 2. 5 mg produced a significantly higher overall objective response rate ( 24%) compared with MA (16%; logistic regression, P = .04) or letrozole 0.5 mg (13%; P = .004). Duration of objective response was significan tly longer for letrozole 2.5 mg compared with MA (Cox regression, P = .02). Letrozole 2.5 mg was significantly superior to MA and letrozole 0.5 mg in time to treatment failure (P = .04 and P = .002, respectivel y). For time to progression, letrozole 2.5 mg was superior to letrozol e 0.5 mg (P = .02), but not to MA (P = .07). There was a significant d ose effect in overall survival in favor of letrozole 2.5 mg (P = .03) compared with letrozole 0.5 mg. Letrozole was significantly better tol erated than MA with respect to serious adverse experiences, discontinu ation due to poor tolerability, cardiovascular side effects, and weigh t gain. Conclusion: The data show letrozole 2.5 mg once daily to be mo re effective and better tolerated than MA in the treatment of postmeno pausal women with advanced breast cancer previously treated with antie strogens. (C) 1998 by American Society of Clinical Oncology.