Multicenter, phase II trial of exemestane as third-line hormonal therapy of postmenopausal women with metastatic breast cancer

Purpose: To assess the antitumor activity, safety, and hormone-suppressive effects of the irreversible aromatase inactivator, exemestane (Aromasin, Ph armacia & Upjohn, Kalamazoo, MI), administered as third-line hormone therap y to postmenopausal women with metastatic breast cancer that is refractory to tamoxifen and megestrol acetate. Patients and Methods: Exemestane war administered at a dose of 25 mg/d oral ly until patients experienced disease progression, The efficacy and safety of exemestane were clinically and radiographically evaluated, The impact of exemestane treatment on tumor-related signs and symptoms was assessed. The effect of exemestane on serum levels of estrogens and other steroidal horm ones was determined. Results: Ninety-one patients were treated, There were four complete respons es (CR) and eight partial responses (PR), for an objective response rate of 13% in the entire treated population, The overall success rate (CR, PR, or stable disease [SD] greater than or equal to 24 weeks) was 30%, The median duration of response and overall success was 9 months and 8 months, respec tively. Most patients with CR/PR (83%; 10 of 12 patients) and SD greater th an or equal to 24 weeks (80% 12 of 15 patients) had improved or stable tumo r-related signs and symptoms. Mean levels of circulating estrone (E-1), est radiol (E-2), and estrone sulfate decreased to 11%, 22%, and 13% of baselin e levels, respectively (at week 8 or 16 of treatment). One half of the pati ents had undetectable E-1 and E-2 levels during treatment, including at the time of disease progression. Mild nausea (20% of patients) and hot flashes (20%) were the most common drug-related adverse events and were generally grade 1. Conclusion: Exemestane is an active and well-tolerated third-line hormonal therapy that represents a new treatment option for postmenopausal patients with advanced breast cancer that has become refractory to standard first- a nd second-line hormonal therapies. (C) 1999 by American Society of Clinical Oncology.