FULVESTRANT AS FIRST-LINE TREATMENT FOR ADVANCED BREAST CANCER IN POSTMENOPAUSAL WOMEN AFTER PROGRESSION ON PRIOR ADJUVANT THERAPY WITH THIRD-GENERATION AROMATASE INHIBITORS: A PHASE II TRIAL

The aim of this phase II study was to evaluate the activity and safety of fulvestrant in postmenopausal hormone-sensitive women with advanced breast cancer (ABC) progressing after adjuvant treatment with AI. The primary end point was time to progression (TTP) and the secondary end point was the clinical benefit (CB) rate. Fifty-two consecutive patients were enrolled: median age of 67 years (range 35-78); ECOG performance status of 0-1 in 90%. Anthracycline-based adjuvant chemotherapy had been given in 45% of patients, with sequential hormonal therapy, and 92% of patients had received radiotherapy. The prior endocrine therapy consisted of anastrozole in 51% of patients, letrozole in 34%, and exemestane switching from tamoxifen in 15% of patients (adjuvant setting only). Disease-free-interval was 5 years in 45%. Dominant metastatic sites were viscera (liver/lung in 72% of cases) and bone (20% of cases). Fulvestrant was administered at registered dose of 250 mg via intramuscular injection every 28 days, until disease progression or other reason for discontinuation. Treatment allowed good patient compliance, with mild-moderate side effects (hot flashes 30%, fatigue 25%, headache 10%, injection site reactions 8%, nausea 5%). The median number of given cycles was 6 (range 4-12+). Nine out of 52 patients (17%, 95% CI 9.3% to 29.7%) achieved an objective response, with one complete and 8 partial remissions (3 in the lung, 4 in the liver and 2 in soft tissue sites); median response duration was 14.5 months (range 4-22 months). In addition, 16 patients had stable disease lasting 6-18 months, for an overall CB rate of 48% (95% CI 35.1% to 61.3%). Median TTP was 6 months (6-22). Our results confirm that fulvestrant is a well-tolerated and effective strategy as first-line treatment in hormone-sensitive postmenopausal women who had progressed after prior adjuvant treatment with third-generation IA. The good treatment compliance and the possibility to delay the less-tolerated chemotherapy option could positively affect patient’s quality of life