HAMBURG, Germany—The steroidal aromatase inactivator exemestane(Drug information on exemestane) (Aromasin) is safe and provides superior progression-free survival, compared with tamoxifen(Drug information on tamoxifen), in the treatment of postmenopausal woman diagnosed with hormone-responsive metastatic breast cancer, according to the first head-to-head front-line phase III trial comparing the two agents. Robert Paridaens, MD, of the University Hospital Gasthuisberg, Leuven, Belgium, presented the findings at the 4th European Breast Cancer Conference (abstract 241).
The EORTC’s (European Organization for Research and Treatment of Cancer) Specialized Breast Group initiated the randomized, open-label, phase II-III trial in 1996. The trial aimed to further document the safety profile of exemestane and to determine if exemestane-treated patients had at least a 3-month increase in progression-free survival over tamoxifen. "This trial was initiated as a phase II study with the possibility of extending to phase III if results were promising," Dr. Paridaens said.
Patients with measurable disease were enrolled in the trial if they had not received hormone therapy for metastatic breast cancer and had either a hormone-receptor-positive cancer or an unknown status with a long disease-free period. Patients were randomized to exemestane 25 mg daily or tamoxifen 20 mg daily.
The results of the initial phase II study, which included 122 patients, showed a promising overall response rate, clinical benefits rate, and response duration favoring exemestane. Furthermore, serious toxicity was low, and exemestane was generally well tolerated, with no adverse effects on the lipid profile. As a result, the investigators decided to extend the study to phase III. Between October 1996 and July 2002, 382 patients from 81 institutions in 25 countries were recruited to participate in the phase III trial.
Data analysis showed a median progression-free survival for patients taking exemestane of 9.95 months, compared with 5.72 months for those on tamoxifen.
Response rates were also higher in the exemestane arm: 7.4% complete response (14 patients) and 36.8% partial response (71 patients) for exemestane, compared with 2.6% (5 patients) and 26.6% (52 patients), respectively, for tamoxifen. Dr. Paridaens said that regardless of the site of the metastasis, the investigators generally saw more responses in patients taking exemestane than in those taking tamoxifen.
To date, 284 (74%) of the participating patients have experienced disease progression or have died. The investigators are currently assessing the trial data further, and the complete overall survival data will be released later this year.
"The main endpoint of treatment in advanced disease is control of symptoms—in other words, progression-free survival with the fewest possible adverse effects because maintaining quality of life in incurable disease is essential," Dr. Paridaens said. He noted that both aromatase inhibitors and tamoxifen are often associated with hot flushes and menopausal symptoms.
Further, women taking aromatase inhibitors often complain about joint and muscular aches. However, the aromatase inhibitors are less likely than tamoxifen to be associated with thromboembolic events, and, unlike tamoxifen, they are not associated with an increased risk of endometrial cancer.
According to Dr. Paridaens, one interesting finding emerging from this study is the lack of adverse effects on the patients’ lipid profile with exemestane. "This contrasts with results seen in studies of nonsteroidal aromatase inhibitors," he said. "Whether this will translate into greater long-term cardiovascular safety or whether it is an indication for use of exemestane in woman with abnormal lipid measurements needs to be demonstrated in future clinical studies."
Based on the study outcomes, the investigators concluded that exemestane is a good choice for first-line treatment in hormone-responsive metastatic breast cancer. Further, Dr. Paridaens said, its safety profile makes it an attractive option for adjuvant therapy or to prevent breast cancer in high-risk women.
