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, Pharmacia and Upjohn, Kalamazoo, MI), administered as third-line hormone therapy to postmenopausal women with metastatic breast cancer that is refractory to tamoxifen and megestrol acetate. Patients and Methods: Exemestane was administered at a dose of 25 mg/d orally 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 hormones was determined. Results: Ninety-one patients were treated. There were four complete responses (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] ≥ 24 weeks) was 30%. The median duration of response and overall success was 9 months and 8 months, respectively. Most patients with CR/PR (83%; 10 of 12 patients) and SD ≥ 24 weeks (80%; 12 of 15 patients) had improved or stable tumor-related signs and symptoms. Mean levels of circulating estrone (E₁), estradiol (E₂), and estrone sulfate decreased to 11%, 22%, and 13% of baseline levels, respectively (at week 8 or 16 of treatment). One half of the patients had undetectable E₁ and E₂ 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- and second-line hormonal therapies.