A comparison of high-dose (HD, 500 mg) fulvestrant vs anastrozole (1 mg) as first-line treatments for advanced breast cancer: results from FIRST.

Abstract

Abstract Abstract #6126 Background: The estrogen-receptor (ER) antagonist fulvestrant (Faslodex™) at the approved dose (AD, 250mg) has confirmed efficacy in postmenopausal women with advanced breast cancer following recurrence or progression on an anti-estrogen. However, evidence suggests that higher doses may have greater biological and clinical activity. A recent neoadjuvant study in patients with ER+, locally advanced disease showed significantly greater reductions in Ki67 LI and ER expression for fulvestrant high dose (HD, 500 mg) compared with AD.
 Methods: FIRST (Fulvestrant fIRst-line Study comparing endocrine Treatments) is a Phase II, randomized, open-label, multicentre study comparing fulvestrant HD (500 mg/month [2×250 mg im injections] plus 500 mg on Day 14 of Month 1) vs anastrozole (1 mg/day) as first-line treatments for postmenopausal women with advanced breast cancer. Eligible patients had no prior treatment for advanced disease and ER+, evaluable disease. Patients received treatment until disease progression or an event necessitating discontinuation. The primary endpoint was clinical benefit rate (CBR), ie the proportion of patients achieving a complete response, a partial response or stable disease for ≥24 weeks. Secondary endpoints included: objective response (OR), time to progression (TTP), duration of response (DoR), duration of clinical benefit (DoCB) and tolerability (adverse events [AEs] and laboratory tests).
 Results: In total, 205 women (median age 67 years) were included (fulvestrant HD: n=102; anastrozole: n=103). Median follow-up was 6.5 months. CBR was similar between treatments: fulvestrant HD 72.5%, anastrozole 67.0% (odds ratio 1.3023, 95% confidence interval [CI] 0.7170, 2.3976, p=0.3860). OR rates were: fulvestrant HD 36%, anastrozole 35.5%. Median TTP for anastrozole: 12.5 months; fulvestrant HD: not yet reached, corresponding to a 60% longer TTP for fulvestrant HD (hazard ratio=0.6266, 95% CI 0.3929, 0.9991, p=0.0496). DoR and DoCB were also numerically longer for fulvestrant HD. Both treatments were well tolerated, with no significant differences in the incidence of pre-specified AEs or the small number of withdrawals due to AEs.
 Discussion: Fulvestrant HD offers CB and OR rates similar to those obtained with anastrozole 1 mg, with a significantly longer TTP. Fulvestrant HD was well tolerated, with no unexpected AEs. The AE profile of fulvestrant HD appears consistent with the known toxicity profile of the AD. These results are encouraging and provide further support for the improved clinical activity anticipated with fulvestrant HD. Confirmation of these findings is awaited from an ongoing Phase III, double-blind comparison of fulvestrant HD and AD (CONFIRM). Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6126.