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Activity of Exemestane in Metastatic Breast Cancer After Failure of Nonsteroidal Aromatase Inhibitors: A Phase II Trial

From the Department of Oncology, Haukeland University Hospital, Bergen, Norway; Istituto Nazionale Tumori and Pharmacia & Upjohn, Milan, Italy; Peter MacCallum Cancer Institute, East Melbourne, Victoria, Australia; Centre Rene Huguenin, St Cloud, France; Marin Oncology Associates Inc, Greenbrae, CA; Instituto A.H. Roffo, Buenos Aires, Argentina; the Netherlands Cancer Institute, Amsterdam, the Netherlands; and Pharmacia & Upjohn, Kalamazoo, MI.

Address reprint requests to Per Eystein Lønning, MD, Department of Oncology, Haukeland University Hospital, Bergen, N-5021, Norway; email plon{at}haukeland.no

PURPOSE: To evaluate the antitumor activity and toxicity of a new steroidal aromatase inactivator, exemestane, in postmenopausal women with metastatic breast cancer who had progressive disease (PD) after treatment with a nonsteroidal aromatase inhibitor.

PATIENTS AND METHODS: In this phase II trial, eligible patients were treated with exemestane 25 mg daily (n = 241) followed, at the time PD was determined, by exemestane 100 mg daily (n = 58).

RESULTS: On the basis of the intent-to-treat analysis by independent review, exemestane 25 mg produced objective responses in 6.6% of patients (95% confidence interval [CI], 3.8% to 10.6%) and overall success (complete response + partial response + no change for 24 weeks or longer) in 24.3% (95% CI, 19.0% to 30.2%). The median durations of objective response and overall success were 58.4 weeks (95% CI, 49.7 to 71.1 weeks) and 37.0 weeks (95% CI, 35.0 to 39.4 weeks), respectively. Increasing the dose of exemestane to 100 mg upon the development of PD produced one partial response (1.7%; 95% CI, 0.0% to 9.2%). Both dosages were well tolerated and were discontinued because of adverse events in only 1.7% of patients.

CONCLUSION: Exemestane 25 mg once daily seems to be an attractive alternative to chemotherapy for the treatment of patients with metastatic breast cancer after multiple hormonal therapies have failed.

Preliminary findings of this study have previously been published in abstract form (Lønning PE, Bajetta E, Murray R, et al: A phase II study of exemestane (EXE) in metastatic breast cancer (MBC) patients failing nonsteroidal aromatase inhibitors (ns-AIs). Breast Cancer Res Treat 50:304, 1998 [abstr 435]).

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