Exemestane improves survival in metastatic breast cancer: results of a phase III randomized study.

Abstract We compared the efficacy and safety of the oral aromatase inactivator exemestane (EXE) with megestrol acetate (MA) in women with metastatic breast cancer. This phase III randomized, double-blind, multicenter study was conducted in 769 postmenopausal women who had experienced tamoxifen failure. Treatment arms consisted of EXE 25 mg once daily (n = 366) or MA 40 mg four times daily (160 mg daily; n = 403). Peerreviewed, intent-to-treat analyses demonstrated that EXE induced a trend toward higher rates of complete response (CR) + partial response (PR) (15.0% vs. 12.4%) and of CR + PR + stable disease (SD) ≥ 24 weeks (37.4% vs. 34.6%), but differences were not statistically significant. Statistically significant differences favoring EXE were seen in median duration of CR + PR + SD ≥ 24 weeks (60.1 vs. 49.1 weeks; P = 0.025), time to tumor progression (20.3 vs. 16.6 weeks; P = 0.037), time to treatment failure (16.3 vs. 15.7 weeks; P = 0.042), and overall survival (not reached vs. 123.4 weeks; P = 0.039). Both treatments were well tolerated, but MA was associated with more grade 3 or 4 weight gain (8% vs. 17%, P = 0.001); the pain score was similar in both groups. There was a trend toward superiority in treatment-related signs and symptoms (TRSS) with EXE. There was greater improvement in the pain score and TRSS in patients achieving an objective response with EXE vs. MA. Quality of life improved or was similar for EXE in most domains. Exemestane offers an important new treatment option for postmenopausal women with hormone-responsive breast cancer.