Abstract S1-3: A Comparison of Fulvestrant 500 mg with Anastrozole as First-Line Treatment for Advanced Breast Cancer: Follow-Up Analysis from the ‘FIRST’ Study

Background: Fulvestrant 250 mg has been shown to be at least as effective as anastrozole as second-line endocrine therapy for advanced hormone receptor-positive (HR+) breast cancer. However, there are biological and clinical data suggesting that fulvestrant 500 mg is more effective than 250 mg. The Fulvestrant First-Line Study Comparing Endocrine Treatments (FIRST) was designed to compare fulvestrant 500 mg with anastrozole in the first-line setting. The primary analysis reported that fulvestrant 500 mg was at least as effective as anastrozole in terms of clinical benefit rate and objective response rate. At data cut-off for the primary analysis, performed 6 months after the last patient (pt) was randomized, 117 (57.1%) pts were receiving study treatment, and median time to progression (TTP) was not reached for fulvestrant 500 mg vs 12.5 months for anastrozole (HR 0.63; 95% CI 0.39, 1.00; p=0.0496). Here, we report a follow-up data analysis of TTP and time to treatment failure (TTF). Methods: This was a Phase II, randomized, open-label, multicenter study comparing fulvestrant 500 mg (500 mg i.m. on Day 0, then 500 mg i.m. on Days 14 and 28 and every 28 days thereafter) with anastrozole (1 mg/day p.o.) as first-line treatment for postmenopausal women with advanced breast cancer. Follow-up analysis was performed when 79.5% of pts had discontinued study treatment. TTP was defined by RECIST before data cut-off for the primary analysis, and investigator opinion after data cut-off. TTF was defined as time from randomization to cessation of trial therapy. In the fulvestrant 500 mg group, TTF was derived as last injection plus 14 days, representing the midpoint in the window where treatment was withdrawn. Best overall response to first subsequent breast cancer therapy, WHO-PS, and serious AEs are also reported. Results: A total of 205 pts received fulvestrant 500 mg (n=102) or anastrozole (n=103). At this follow-up analysis with data cut-off March 26 2010, median follow-up for TTP across both treatment groups was 16.5 months. Median TTP was 23.4 months for the fulvestrant 500 mg group vs 13.1 months for the anastrozole group, corresponding to a 35% reduction in risk of progression (HR 0.66; 95% CI 0.47, 0.92; p=0.01). Median TTF was 17.6 months vs 12.7 months for the fulvestrant 500 mg and anastrozole groups, respectively (HR 0.73; 95% CI 0.54, 1.00; p=0.05). The best overall response to subsequent therapy was similar between the treatment groups (including 15 pts [23.8%] in the fulvestrant 500 mg group and 15 pts [21.1%] in the anastrozole group with either a complete or partial response) and there were no clinically important differences in terms of WHO-PS. Fulvestrant 500 mg was well tolerated and no new safety concerns were documented. Conclusion: With significantly longer follow-up, the TTP and TTF results from this analysis are consistent with the analysis of TTP at the primary data cut-off. Taken together, these results suggest an efficacy benefit for fulvestrant 500 mg compared with anastrozole as first line endocrine therapy for pts with HR+ advanced breast cancer. These data provide further support that if fulvestrant is used in advanced breast cancer then the preferred dose should be 500 mg. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S1-3.