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

TLDR

This phase III, double‑blind, randomized, multicenter study evaluated the efficacy, pharmacodynamics, and safety of exemestane versus megestrol acetate in postmenopausal women with progressive advanced breast cancer who had failed tamoxifen. A total of 769 patients were randomized to receive exemestane 25 mg/day or megestrol acetate 40 mg four times daily, and tumor response, duration of control, tumor‑related signs and symptoms, quality of life, survival, and tolerability were assessed. Exemestane produced higher objective response rates (15.0 % vs 12.4 %), longer median survival (not reached vs 123.4 weeks), extended duration of overall success (60.1 vs 49.1 weeks), delayed tumor progression (20.3 vs 16.6 weeks), and treatment failure (16.3 vs 15.7 weeks), with comparable or better pain, TRSS, and QOL, and a better safety profile, including fewer grade 3/4 weight changes.

Abstract

PURPOSE: This phase III, double-blind, randomized, multicenter study evaluated the efficacy, pharmacodynamics, and safety of the oral aromatase inactivator exemestane (EXE) versus megestrol acetate (MA) in postmenopausal women with progressive advanced breast cancer who experienced failure of tamoxifen. 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, duration of tumor control, tumor-related signs and symptoms (TRSS), quality of life (QOL), survival, and tolerability were evaluated. RESULTS: Overall objective response (OR) rates were higher in patients treated 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 survival 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 ≥ 24 weeks; 60.1 v 49.1 weeks; P = .025), time to tumor progression (20.3 v 16.6 weeks; P = .037), and time to treatment failure (16.3 v 15.7 weeks; P = .042). Compared with MA, there 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 common 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 treatment option for postmenopausal women with progressive advanced breast cancer who experienced failure of tamoxifen.