Exemestane is superior to megestrol acetate after tamoxifen failure in postmenopausal women with advanced breast cancer: Results of a phase III randomized double-blind trial

Purpose: This phase ill, double-blind, randomized, multicenter study evalua ted the efficacy, pharmacodynamics, and safety of the oral aromatase inacti vator exemestane (EXE) versus megestrol acetate (MA) in postmenopausal wome n with progressive advanced breast cancer who experienced failure of tamoxi fen. Patients and Methods: A total of 769 patients were randomized to EXE 25 mg/ d (n = 366) or MA (n = 403) 40 mg four times daily. Tumor response, duratio n of tumor control, tumor-related signs and symptoms (TRSS), quality of lif e (QOL), survival, and tolerability were evaluated. Results: Overall objective response (OR) rates were higher in patients trea ted with EXE than in those treated with MA (15.0% v 12.4%); a similar trend was noted in patients with visceral metastases (13.5% v 10.5%), Median sur vival time was significantly longer with EXE (median not reached) than with MA (123.4 weeks; P = .039), as were the median duration of overall success (OR or stable disease greater than or equal to 24 weeks; 60.1 v 49.1 weeks ; P = .025), time to tumor progression (20.3 v 16.6 weeks; P = .037), and t ime to treatment failure (16.3 v 15.7 weeks; P = .042). Compared with MA, t here were similar or greater improvements in pain, TRSS, and QOL with EXE. Both drugs were well tolerated. Grade 3 or 4 weight changes were more commo n with MA (17.1% v 7.6%; P = .001). Conclusion: EXE prolongs survival time, time to tumor progression, and time to treatment failure compared with MA and offers a well-tolerated treatmen t option for postmenopausal women with progressive advanced breast cancer w ho experienced failure of tamoxifen. (C) 2000 by American Society of Clinic al Oncology.