Background: A clinically significant improvement in median overall survival (OS) has been reported for fulvestrant 500 mg vs fulvestrant 250 mg (26.4 months vs 22.3 months, respectively; hazard ratio [HR] 0.81; 95% confidence interval (CI) 0.69, 0.96; nominal p=0.02) in the Phase III COmparisoN of Faslodex In Recurrent or Metastatic breast cancer (CONFIRM) study, following failure on prior endocrine therapy. Therefore, further evidence for OS effects of fulvestrant 500 mg was sought.

The Fulvestrant fIRst-line Study comparing endocrine Treatments (FIRST) compares fulvestrant 500 mg with anastrozole in the earlier first-line treatment setting for postmenopausal women with hormone receptor-positive (HR+) advanced breast cancer. In the primary analysis (6 months after last patient was randomized) fulvestrant 500 mg was at least as effective as anastrozole for clinical benefit rate (primary endpoint) and showed a significantly longer time to progression (TTP; median TTP not reached for fulvestrant 500 mg vs 12.5 months for anastrozole; HR 0.63; 95% CI 0.39, 1.00; p=0.05). In a follow-up analysis when 79.5% of patients (pts) had discontinued study treatment, median TTP was 23.4 months for fulvestrant 500 mg vs 13.1 months for anastrozole (HR 0.66; 95% CI 0.47, 0.92; p=0.01). Here we report OS from FIRST.

Methods: FIRST is a Phase II, randomized, open-label, multicenter study (NCT00274469) comparing fulvestrant 500 mg (500 mg im on Days 0, 14 and 28, and every 28 days thereafter) with anastrozole (1 mg/day po). Pts were postmenopausal women with locally advanced or metastatic HR+ breast cancer who had not received prior endocrine therapy for locally advanced or metastatic disease. Kaplan-Meier curves of OS (time from randomization to death from any cause) will be compared by unadjusted log-rank test. Pts not known to have died including those lost to follow-up or with no survival information will be right-censored at last known date alive. Serious adverse events will also be reported.

Results: In total, 205 pts (median age 67.0 years) were randomized from 62 centers in 9 countries (fulvestrant 500 mg: n=102; anastrozole: n=103). The first pt enrolled on Feb 6, 2006. As of May 14, 2014, 40/205 pts (19.5%) were alive across both treatment groups. 4 pts (2.0%) were lost to follow-up, 130 pts (63.4%) had died, and 31 pts [15.1%] did not participate in the OS follow-up (20 pts due to non-participation of center in the OS follow-up; other reasons included withdrawal of consent). A total of 130 events had occurred; preliminary data indicate a median OS of 50 months in the total study population. Data cut-off is planned for when approximately 65% pts have died, expected in Aug 2014. Comparative data between fulvestrant 500 mg and anastrozole for OS will be presented.

Conclusions: We understand FIRST to be the only study that has demonstrated improved efficacy (ie TTP) for an alternative hormone therapy over a third-generation aromatase inhibitor for treatment of HR+ advanced breast cancer. Improved OS results would provide additional support for superior efficacy of fulvestrant 500 mg over anastrozole as first-line endocrine therapy for postmenopausal women with HR+ locally advanced or metastatic breast cancer.

Citation Format: John FR Robertson, Antonio Llombart-Cussac, David Feltl, John Dewar, Marek Jasiówka, Nicola Hewson, Yuri Rukazenkov, Matthew J Ellis. Fulvestrant 500 mg versus anastrozole as first-line treatment for advanced breast cancer: Overall survival from the Phase II ‘FIRST’ study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr S6-04.