`
`2014 San Antonio Breast Cancer Symposium
`
`Title: Fulvestrant 500 mg versus anastrozole asfirst-line treatment for advanced breast cancer: overall survival from the phaseII
`‘first’ study
`
`John FR Robertson’, Antonio Llombart-Cussac’, David Feltl®, John Dewar’, Marek Jasiéwka®, Nicola Hewson®, Yuri Rukazenkov®
`and Matthew J Ellis’. 'University of Nottingham, Derby, Nottingham, United Kingdom; *Hospital Arnau de Vilanova, Lérida, Spain;
`SFNsP Ostrava, Radioterapeuticka Klinika, Ostrava-Poruba, Czech Republic; ‘Ninewells Hospital and Medical School, Dundee,
`United Kingdom; °Centrum Onkologii, Instytut im Marii Sklodowskiej-Curie, Krakéw, Poland; AstraZeneca Pharmaceuticals,
`Macclesfield, United Kingdom and ‘Washington University School of Medicine, St Louis, MO.
`
`Body: Background: Fulvestrant 500 mg showedaclinically 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 (Cl) 0.69, 0.96; nominal
`p=0.02) in the Phase III CONFIRM study, for patients (pts) with hormone receptor positive (HR+) disease following failure on prior
`endocrine therapy. Further evidence for OS effects of fulvestrant 500 mg was soughtin the FulvestrantflRst-line Study comparing
`endocrine Treatments (FIRST), which compared fulvestrant 500 mg with anastrozole asfirst-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 monthsfor fulvestrant 500 mg vs 13.1 months for anastrozole (HR 0.66;
`95% Cl 0.47, 0.92; p=0.01). Here we report the only scheduled FIRST OS analysis.
`Methods: FIRST, a PhaseII, 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-ranktest 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 wereright-censored at last known datealive, 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). Thefirst pt enrolled on Feb 6, 2006. As of July 2014, 33/205 pts (16.1%) were knownto be alive across both
`treatment groups and 137/205 (66.8%) pts had died. Median OS wassignificantly greater for fulvestrant 500 mg (54.1 months) vs
`anastrozole (48.4 months; HR 0.70; 95% Cl 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 receivingfirst-line ftulvestrant 500 mglived significantly longer than pts on anastrozole (median OS
`difference of 5.7 months). A consistent OS treatment effect was observed across predefined subgroups. FIRSTis 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 asfirst-line endocrine therapy for postmenopausal women with HR+ LA or MBC. If confirmation of superiority for
`fulvestrant 500 mg is seen in the PhaseIII FALCON study (NCT01602380), fulvestrant 500 mg should be considered for approval
`as a first-line agent in this setting.
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`AstraZeneca Exhibit 2057 p. 1
`InnoPharma Licensing LLC v. AstraZeneca AB IPR2017-00904
`Fresenius-Kabi USA LLC v. AstraZeneca AB IPR2017-01910
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