Publication Number: S6—04
`
`2014 San Antonio Breast Cancer Symposium
`
`Title: Fulvestrant 500 mg versus anastrozole as first-line treatment for advanced breast cancer: overall survival from the phase II
`
`‘first’ study
`
`John FR Robertson‘, Antonio Llombart-Cussacz, David FeItI3, John Dewar“, Marek Jasiowka5, Nicola Hewsone, Yuri Rukazenkove
`
`and Matthew J Ellis’. ‘University of Nottingham, Derby, Nottingham, United Kingdom; 2Hospita| Arnau de Vilanova, Lérida, Spain;
`
`3FNsP Ostrava, Radioterapeuticka Klinika, Ostrava-Poruba, Czech Republic; “NineweIIs Hospital and Medical School, Dundee,
`
`United Kingdom; 5Centrum Onkologii, Instytut im Marii Sklodowskiej—Curie, Krakow, Poland; 6AstraZeneca Pharmaceuticals,
`
`Macclesfield, United Kingdom and 7Washington University School of Medicine, St Louis, MO.
`
`Body: Background: Fulvestrant 500 mg showed a clinically significant improvement in median overall survival (OS) vs
`
`fulvestrant 250 mg (26.4 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 CONFIRM study, for patients (pts) with hormone receptor positive (H R+) disease following failure on prior
`
`endocrine therapy. Further evidence for OS effects of fulvestrant 500 mg was sought in the Fulvestrant fIRst-line Study comparing
`
`endocrine Treatments (FIRST), which compared fulvestrant 500 mg with anastrozole as first-line treatment for postmenopausal
`
`pts with HR+ locally advanced (LA) or metastatic breast cancer (MBC). In the primary analysis, fulvestrant 500 mg was as
`
`effective as anastrozole for clinical benefit rate (primary endpoint) and significantly better for time to progression (TTP; secondary
`
`endpoint). In a follow—up analysis, 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 the only scheduled FIRST OS analysis.
`
`Methods: FIRST, a Phase II, randomized, open-label study (NCT00274469), compared fulvestrant 500 mg (im on Days 0, 14 and
`
`28, and every 28 days thereafter) with anastrozole (1 mg/day po). Pts had not received prior endocrine therapy for advanced
`
`disease. OS (time from randomization to death) was compared by unadjusted log-rank test after approximately 65% of deaths.
`
`Effect of treatment on OS was examined across subgroups (including age, hormone receptor status and visceral disease). Pts
`
`alive or not known to have died were right—censored at last known date alive, including 20 pts in centers invited but who did not
`
`join the OS follow-up phase. Serious adverse events (SAEs) were recorded.
`
`Results: 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 July 2014, 33/205 pts (16.1%) were known to be alive across both
`
`treatment groups and 137/205 (66.8%) pts had died. Median OS was significantly greater for fulvestrant 500 mg (54.1 months) vs
`
`anastrozole (48.4 months; HR 0.70; 95% CI 0.50, 0.98; p=0.041). OS analyses in pre-specified subgroups demonstrated a
`
`consistent treatment effect for fulvestrant 500 mg vs anastrozole (global interaction test p=0.755). The frequency of SAEs was
`
`similar between fulvestrant 500 mg (23.8%) and anastrozole (21.4%).
`
`Conclusions: HR+ pts receiving first-line fulvestrant 500 mg lived significantly longer than pts on anastrozole (median OS
`
`difference of 5.7 months). A consistent OS treatment effect was observed across predefined subgroups. FIRST is therefore the
`
`second randomized trial to show an OS advantage for fulvestrant 500 mg over another endocrine therapy. No new safety signals
`
`were identified with longer-term treatment. Improved OS data provide further support for superior efficacy of fulvestrant 500 mg
`
`over anastrozole as first-line endocrine therapy for postmenopausal women with HR+ LA or MBC. If confirmation of superiority for
`
`fulvestrant 500 mg is seen in the Phase III FALCON study (NCT01602380), fulvestrant 500 mg should be considered for approval
`
`as a first-line agent in this setting.
`
`AstraZeneca EX. 2057 p. 1
`Mylan Pharms. Inc. V. AstraZeneca AB IPR2016—01325