Fulvestrant 500 mg Is Well-Tolerated and Efficacious in Women with Locally Advanced Breast Cancer

Fulvestrant is a complete estrogen receptor (ER) antagonist that represents an endocrine therapy for patients with ER-positive metastatic breast cancer who have disease progression after previous treatment with an antiestrogen. At a 500-mg monthly dose, fulvestrant has a disease control rate ranging from 45% to 72%, and a progression-free survival (PFS) that ranges from 6.5 months to 23 months depending on whether it is used as first-line therapy or later. In this observational prospective trial, fulvestrant 500 mg was evaluated in unselected patients with locally advanced breast cancer.

Eligible patients in this study were women with locally advanced breast cancer who were suitable candidates for endocrine therapy and who (1) had received previous treatment with either an antiestrogen or aromatase inhibitor as a first-line therapy, or (2) had relapsed while on or within 1 year of completion of adjuvant endocrine therapy. Maintenance treatment after chemotherapy for advanced disease was allowed. The primary end point was the clinical benefit rate (CBR), which was defined as the sum of the rates for complete response, partial response, and stable disease lasting >24 weeks. Secondary end points were overall survival (OS), PFS, and tolerability.

Of the 163 enrolled patients, 55% had received first-line endocrine therapy and 74% had received previous adjuvant endocrine therapy during their course of treatment. Overall, CBR was reached in 59% of patients receiving fulvestrant 500 mg (95% confidence interval [CI], 51%-66%). Median PFS was 7 months (95% CI, 6-8 months), and median OS was 35 months (95% CI, 24-46 months). “Endocrine-sensitive patients had a better PFS and OS compared to those who were not sensitive,” said Dr Luca Moscetti of Viterbo, Italy, who was affiliated with this study. The safety analysis did not show any relevant toxicity, and no serious adverse events were observed.

In performing a multivariate analysis, visceral involvement (occurring in 44% of these patients) was observed to be a prognostic factor for PFS (hazard ratio [HR], 1.60; 95% CI, 1.13-2.27; P = 0.008), whereas previous endocrine therapy (HR, 2.11; 95% CI, 1.27-3.29; P = 0.004) and having more than 1 site of metastasis (52% of patients) (HR, 2.53; 95% CI, 1.54-4.22; P <0.0001) were prognostic factors for OS. Having ER level expression >50% (odds ratio [OR], 3.49; 95% CI, 1.30-9.38; P = 0.01), a single site of metastasis (OR, 2.21; 95% CI, 1.08-4.50; P = 0.03), or no previous endocrine therapy for advanced disease (OR, 2.24; 95% CI, 1.1-4.58; P = 0.03) were predictive factors for CBR.

Overall, fulvestrant was shown to be very well tolerated, and the efficacy of the 500-mg dose was confirmed in daily clinical practice. Higher values of ER (≥50%) were correlated to a higher CBR, and patients who had received first-line endocrine therapy had a poorer prognosis and a reduced CBR compared with those who were endocrine therapy–naïve.

Moscetti L, et al. ESMO 2016. Abstract 265P.