• Flemming J, Madarnas Y, Franek J, Breast Cancer Disease Site Group. Fulvestrant for systemic therapy of locally advanced or metastatic breast cancer in postmenopausal women: guideline recommendations. Toronto (ON): Cancer Care Ontario Program in Evidence-based Care; 2008 Sep 25. 42 p. (Evidence-based series; no. 1-13). [85 references]

1. Patients with NO prior endocrine or cytotoxic therapy for advanced disease and NO recent adjuvant therapy (within previous twelve months)

   Fulvestrant is NOT recommended as an alternative to tamoxifen for first-line therapy of locally advanced or metastatic breast cancer in postmenopausal women who have had no prior endocrine or cytotoxic therapy for advanced disease and no recent adjuvant endocrine therapy (within previous twelve months).

2. Patients who have recurred on prior adjuvant endocrine therapy or have progressed on prior endocrine therapy for advanced disease

   Fulvestrant may be considered as alternative therapy to anastrozole for locally advanced or metastatic breast cancer in postmenopausal women with hormone-receptor-positive (estrogen-receptor-positive [ER+] and/or progesterone-receptor-positive [PgR+]) breast cancer that has recurred on prior adjuvant tamoxifen therapy or progressed on prior tamoxifen therapy for advanced disease. Clinicians should be aware of the methodological concerns of the key evidentiary trials used in formulating this recommendation.

   Factors that may influence the choice of fulvestrant versus anastrozole therapy include a slightly decreased, although still significant, incidence of joint disorders and the potential for improved compliance with fulvestrant.

   Fulvestrant may be considered as alternative therapy to exemestane for locally advanced or metastatic breast cancer in postmenopausal women with hormone-receptor-positive (ER+ and/or PgR+) breast cancer that has recurred on prior adjuvant nonsteroidal aromatase inhibitor (NSAI) therapy (during or within six months of discontinuation) or progressed on prior NSAI therapy for advanced disease.

   Factors that influence the choice of fulvestrant versus exemestane therapy include the potential for improved compliance in favour of fulvestrant.

3. Recommended dosage

   The recommended dose of fulvestrant for the treatment of locally advanced or metastatic breast cancer is 250 mg intramuscularly (IM) every month OR a loading dose schedule of 500 mg IM day 0, 250 mg IM on days 14 and 28, and 250 mg IM injection every (q) monthly thereafter.

   Factors that may influence the choice of a loading dose include a shortened time to reach steady state (within one month vs. three to six months for standard dosage) although this may require further verification.

4. Combination Fulvestrant

   At present there are no published studies to guide a recommendation regarding the use of fulvestrant in combination with other chemotherapies for first-line or greater treatment of locally advanced or metastatic breast cancer. There are currently two active, ongoing Phase III trials (Southwest Oncology Group [SWOG]-S0226, Functional Assessment of Cancer Therapy [FACT]; see Section 2: Table 5 in the original guideline document) comparing anastrozole vs. anastrozole plus simultaneous fulvestrant for first-line therapy of metastatic breast cancer. In addition, a third, ongoing Phase III trial (Cancer and Leukemia Group B [CALGB]-40302) is examining the use of second-line fulvestrant alone in comparison with the combination of fulvestrant plus lapatinib ditosylate, an epidermal growth factor receptor (EGFR) inhibitor, in human epidermal growth factor receptor 2 (HER2)/neu-positive women (see Table 5 in the original guideline document).

5. Predictive factors of outcome on Fulvestrant therapy

   There is insufficient evidence to guide a definitive recommendation regarding the interpretation of factors to predict an outcome for postmenopausal women undergoing fulvestrant therapy for locally advanced or metastatic breast cancer.

None provided

The recommendations are supported by evidence-based practice guidelines and Phase III trials.

• Flemming J, Madarnas Y, Franek J, Breast Cancer Disease Site Group. Fulvestrant for systemic therapy of locally advanced or metastatic breast cancer in postmenopausal women: guideline recommendations. Toronto (ON): Cancer Care Ontario Program in Evidence-based Care; 2008 Sep 25. 42 p. (Evidence-based series; no. 1-13). [85 references]

Not applicable: The guideline was not adapted from another source.

2008 Sep 25

Program in Evidence-based Care - State/Local Government Agency [Non-U.S.]

The Program in Evidence-based Care (PEBC) is a Province of Ontario initiative sponsored by Cancer Care Ontario and the Ontario Ministry of Health and Long-Term Care.

Cancer Care Ontario
Ontario Ministry of Health and Long-Term Care

Breast Cancer Disease Site Group

The authors wish to declare no conflicts of interest as of the date of this report.

The following is available:

• Browman GP, Levine MN, Mohide EA, Hayward RSA, Pritchard KI, Gafni A, et al. The practice guidelines development cycle: a conceptual tool for practice guidelines development and implementation. J Clin Oncol 1995;13(2):502-12.

None available

This summary was completed by ECRI on January 20, 2009.