Fulvestrant Is Effective for Patients Failing Other Hormonal Therapy

March 1, 2003

BERN, Switzerland-The antiestrogen fulvestrant (Faslodex) is an effective and well-tolerated treatment option for women with heavily pretreated, hormone-sensitive advanced breast cancer, according to an interim analysis from an ongoing study by the Swiss Group for Clinical Cancer Research (SAKK), based in Bern, Switzerland. All of the patients in the study had failed both tamoxifen and an aromatase inhibitor, but 11 of 32 patients (34%) had prolonged clinical benefit on fulvestrant 250 mg every 28 days.

BERN, Switzerland—The antiestrogen fulvestrant (Faslodex) is an effective and well-tolerated treatment option for women with heavily pretreated, hormone-sensitive advanced breast cancer, according to an interim analysis from an ongoing study by the Swiss Group for Clinical Cancer Research (SAKK), based in Bern, Switzerland. All of the patients in the study had failed both tamoxifen and an aromatase inhibitor, but 11 of 32 patients (34%) had prolonged clinical benefit on fulvestrant 250 mg every 28 days.

"As third-line therapy, we still see response or stabilization of the disease in about one-third of patients in this cohort," said Dr. Lucien Perey, a medical oncologist and investigator with SAKK. "It is a very well tolerated drug, with very few side effects—mostly hot flashes and some reaction at the injection site."

Fulvestrant, which has a strong binding affinity for the estrogen receptor without any associated agonist activity, has been shown to have activity comparable to the aromatase inhibitor anastrozole (Arimidex) in postmenopausal women with advanced breast cancer who are progressing on endocrine therapy (Howell A, et al: J Clin Oncol 20: 3396-3403, 2002). In a previously reported study, fulvestrant demonstrated a clinical benefit of 69%, with median response duration of 25 months, in postmenopausal women with tamoxifen-resistant advanced breast cancer (Howell A, et al: Br J Cancer 74: 300-8, 1996).

The SAKK group sought to assess the efficacy of fulvestrant as third-line treatment in patients who progress after both tamoxifen and aromatase inhibitors.

Phase II Multicenter Study

The phase II multicenter study included 36 postmenopausal women (age range 39 to 86 years) with hormone-sensitive advanced breast cancer. All had received one prior aromatase inhibitor (steroidal and nonsteroidal) and tamoxifen, and had either progressed or had not responded to treatment.

Response data are available for 32 patients; 4 patients were not eligible due to protocol violations. Among the 32 evaluable patients, 2 patients (6%) had a partial response and 9 patients (28%) had stable disease for more than 24 weeks, according to Dr. Perey.

Adverse events included hot flashes in seven patients (19%), fatigue in six (17%) loss of appetite in four (11%) and nausea in four (11%). Pain, dysesthesia, or reaction at site of injection was reported for five patients (15%).

"This is a way of prolonging hormonal therapy in these patients, some of whom are quite old," Dr. Perey said. "We can avoid giving them chemotherapy for a while, because we definitely have stabilization of disease for more than 6 months."

Mechanism of Action

Fulvestrant might be expected to show efficacy in patients with tumors resistant to other antiestrogen treatments because it has a different mechanism of action, according to Dr. Perey. The agent binds to estrogen receptors with high affinity (approximately 89% of the binding affinity of estradiol). This blocks the receptor, preventing estrogen binding. In addition, fulvestrant binding triggers a downregulation in estrogen receptor concentration.

Fulvestrant is indicated in the United States for treating hormone receptor-positive metastatic breast cancer in postmenopausal women who progress on antiestrogen therapy.