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`2014 San Antonio Breast Cancer Symposium
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`Title: Fulvestrant 500 mg versus anastrozole as first-line treatment for advanced breast cancer: overall survival from the phase II
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`‘first’ study
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`John FR Robertson‘, Antonio LIombart-Cussacz, David Feltl3, John Dewar“, Marek Jasiowka5, Nicola Hewsone, Yuri Rukazenkov6
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`and Matthew J Ellis7. 1University of Nottingham, Derby, Nottingham, United Kingdom; 2Hospital Arnau de Vilanova, Lérida, Spain;
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`3FNsP Ostrava, Radioterapeuticka Klinika, Ostrava-Poruba, Czech Republic; 4Ninewells Hospital and Medical School, Dundee,
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`United Kingdom; 5Centrum Onkologii, lnstytut im Marii Sklodowskiej-Curie, Krakéw, Poland; 6AstraZeneca Pharmaceuticals,
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`Macclestield, United Kingdom and 7Washington University School of Medicine, St Louis, MO.
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`Body: Background: Fulvestrant 500 mg showed a clinically significant improvement in median overall survival (OS) vs
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`fulvestrant 250 mg (26.4 vs 22.3 months, respectively; hazard ratio [HR] 0.81 ; 95% confidence interval (CI) 0.69, 0.96; nominal
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`p=0.02) in the Phase III CONFIRM study, for patients (pts) with hormone receptor positive (H R+) disease following failure on prior
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`endocrine therapy. Further evidence for OS effects of tulvestrant 500 mg was sought in the Fulvestrant fIRst-Iine Study comparing
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`endocrine Treatments (FIRST), which compared fulvestrant 500 mg with anastrozole as first-line treatment for postmenopausal
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`pts with HR+ locally advanced (LA) or metastatic breast cancer (MBC). In the primary analysis, tulvestrant 500 mg was as
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`effective as anastrozole for clinical benefit rate (primary endpoint) and significantly better for time to progression (TTP; secondary
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`endpoint). In a follow-up analysis, median TTP was 23.4 months for tulvestrant 500 mg vs 13.1 months for anastrozole (HR 0.66;
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`95% CI 0.47, 0.92; p=0.01). Here we report the only scheduled FIRST OS analysis.
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`Methods: FIRST, a Phase II, randomized, open-label study (NCT00274469), compared tulvestrant 500 mg (im on Days 0, 14 and
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`28, and every 28 days thereafter) with anastrozole (1 mg/day p0). Pts had not received prior endocrine therapy for advanced
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`disease. OS (time from randomization to death) was compared by unadjusted log-rank test after approximately 65% of deaths.
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`Effect of treatment on OS was examined across subgroups (including age, hormone receptor status and visceral disease). Pts
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`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
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`join the OS follow-up phase. Serious adverse events (SAEs) were recorded.
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`Results: 205 pts (median age 67.0 years) were randomized from 62 centers in 9 countries (tulvestrant 500 mg: n=102;
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`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
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`treatment groups and 137/205 (66.8%) pts had died. Median OS was significantly greater for fulvestrant 500 mg (54.1 months) vs
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`anastrozole (48.4 months; HR 0.70; 95% CI 0.50, 0.98; p=0.041). OS analyses in pre-specified subgroups demonstrated a
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`consistent treatment effect for tulvestrant 500 mg vs anastrozole (global interaction test p=0.755). The frequency of SAEs was
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`similar between fulvestrant 500 mg (23.8%) and anastrozole (21.4%).
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`Conclusions: HR+ pts receiving first-line tulvestrant 500 mg lived significantly longer than pts on anastrozole (median OS
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`difference of 5.7 months). A consistent OS treatment effect was observed across predefined subgroups. FIRST is therefore the
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`second randomized trial to show an OS advantage for fulvestrant 500 mg over another endocrine therapy. No new safety signals
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`were identified with longer-term treatment. Improved OS data provide further support for superior efficacy of tulvestrant 500 mg
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`over anastrozole as first-line endocrine therapy for postmenopausal women with HR+ LA or MBC. If confirmation of superiority for
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`fulvestrant 500 mg is seen in the Phase III FALCON study (NCT01602380), tulvestrant 500 mg should be considered for approval
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`as a first-line agent in this setting.
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`AstraZeneca Exhibit 2057 p. 1
`InnoPharma Licensing LLC V. AstraZeneca AB IPR2017-00900
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