Final Overall Survival Analysis of CONFIRM Shows a 4.1 Month Difference in Median Overall Survival When Using FASLODEX®

  Final Overall Survival Analysis of CONFIRM Shows a 4.1 Month Difference in
  Median Overall Survival When Using FASLODEX® (fulvestrant) Injection 500 mg
  Compared with 250 mg.1,2

Business Wire

WILMINGTON, Del. -- December 05, 2012

Today, updated overall survival (OS) data for FASLODEX^® (fulvestrant)
Injection in patients with hormone receptor-positive advanced breast cancer
whose disease progressed or recurred following prior endocrine therapy was
presented at the 35^th CTRC-AACR San Antonio Breast Cancer Symposium by the
principal investigator, Angelo Di Leo, MD, Head of the Sandro Pitigliani
Medical Oncology Unit.^1,2,3

The final updated CONFIRM OS, performed at 75% maturity (after a minimum
follow up duration of 50 months), showed a 19% relative reduction in the risk
of death (hazard ratio (HR) 0.81; 95% confidence interval [CI] 0.69-0.96). No
adjustments were made for multiplicity, therefore these data cannot be
considered statistically significant. The median OS for FASLODEX 500 mg and
250 mg was 26.4 months and 22.3 months, respectively.^2

FASLODEX 500 mg increased progression-free survival, the primary end point in
CONFIRM, with a relative risk reduction of 20% (hazard ratio [HR] 0.80; 95%
confidence interval [CI] 0.68-0.94; p=0.006) compared with FASLODEX 250 mg.
Median progression free survival with FASLODEX 500 mg was found to be 6.5
months compared with 5.5 months with FASLODEX 250 mg.

FASLODEX 500 mg is indicated for the treatment of hormone receptor-positive
metastatic breast cancer in postmenopausal women with disease progression
following antiestrogen therapy. FASLODEX is contraindicated in patients with
known hypersensitivity to the drug or to any of its components.
Hypersensitivity reactions, including urticaria and angioedema have been
reported in association with FASLODEX. Please see additional Important Safety
Information below.

Dr Angelo Di Leo said: “We are encouraged by these data showing that
fulvestrant 500 mg was associated with a 4.1-month improvement in median OS
and a 19% relative reduction in the risk of death compared with fulvestrant
250 mg. Overall, with these latest data being consistent with previous OS
analysis, it further increases our confidence in these findings.”^2

“Breast cancer continues to be the leading cause of cancer death in women
around the world.^4 These data from the final overall survival analysis of
CONFIRM, provide further support for the role of FASLODEX 500 mg in extending
lives of appropriate patients with metastatic breast cancer, a devastating
disease,” said Yuri Rukazenkov, MD, Medical Science Director, AstraZeneca
(NYSE: AZN).

CONFIRM was a Phase III, randomized, double-blind, parallel-group, multicenter
trial comparing FASLODEX 500 mg (n=362) and 250 mg (n=374) in postmenopausal
women with estrogen receptor-positive advanced breast cancer, whose disease
progressed or recurred following prior endocrine therapy. OS was a secondary
endpoint in the CONFIRM trial and was initially analyzed at 50% maturity after
a minimum follow-up duration of 18 months.^1 The updated analysis of OS data
from CONFIRM presented today at SABCS was undertaken to obtain final survival
data at 75% maturity after a minimum follow-up duration of 50 months.^2

Important Safety Information About FASLODEX^® (fulvestrant) Injection

  *FASLODEX is contraindicated in patients with known hypersensitivity to the
    drug or to any of its components. Hypersensitivity reactions, including
    urticaria and angioedema have been reported in association with FASLODEX
  *Because FASLODEX ^ is administered intramuscularly, it should be used with
    caution in patients with bleeding diatheses, thrombocytopenia, or in
    patients on anticoagulants
  *FASLODEX is metabolized primarily in the liver. A 250-mg dose is
    recommended in patients with moderate hepatic impairment. FASLODEX has not
    been evaluated in patients with severe hepatic impairment (Child-Pugh
    Class C)
  *Fetal harm can occur when administered to a pregnant woman. Women should
    be advised of the potential hazard to the fetus and to avoid becoming
    pregnant while receiving FASLODEX
  *The most common, clinically significant adverse reactions occurring in ≥5%
    of patients receiving FASLODEX were: injection site pain, nausea, bone
    pain, arthralgia, headache, back pain, fatigue, pain in extremity, hot
    flash, vomiting, anorexia, asthenia, musculoskeletal pain, cough, dyspnea,
    and constipation
  *Increased hepatic enzymes (ALT, AST, ALP) occurred in >15% of FASLODEX
    users and were non dose-dependent

Indication

FASLODEX is indicated for the treatment of hormone receptor-positive
metastatic breast cancer in postmenopausal women with disease progression
following antiestrogen therapy.

Please see full Prescribing Information for FASLODEX.

                                   – ENDS –

NOTES TO EDITORS

About CONFIRM and overall survival

CONFIRM (COmparisoN of FASLODEX In Recurrent or Metastatic breast cancer) was
a Phase III, randomized, double-blind, parallel-group, multicenter trial
comparing FASLODEX 500 mg (n=362) and 250 mg (n=374) in postmenopausal women
with estrogen receptor-positive advanced breast cancer, whose disease
progressed or recurred following prior endocrine therapy. Eligible patients
were randomized 1:1 to FASLODEX 500 mg or 250 mg, and assessed for tumor
progression every 12 weeks. The primary objective was to compare the efficacy
of both treatment groups in terms of progression-free survival. Secondary
objectives included: objective response rate (ORR), clinical benefit rate
(CBR), duration of response, duration of clinical benefit (DoCB), overall
survival, tolerability, and quality of life (QoL).^1

The initial OS analysis conducted at a minimum follow up of 18 months and 50%
maturity, showed no statistically significant difference in OS (HR=0.84; 95%
CI: 0.69-1.03) (p=0.091). The median overall survival was 25.1 months with
FASLODEX 500 mg and 22.8 months with 250 mg. The updated OS analysis,
conducted at a minimum follow up of 50 months and 75% maturity, showed a 19%
relative reduction in the risk of death (hazard ratio (HR) 0.81; 95%
confidence interval (CI) 0.69 to 0.96). No adjustments were made for
multiplicity, therefore these data cannot be considered statistically
significant. The KM estimate showed a sustained separation of the curves and a
median survival of 26.4 months vs 22.3 months for the 500 mg and 250 mg doses,
respectively.^3

About Metastatic Breast Cancer

Metastatic breast cancer occurs when cancer cells spread beyond the initial
tumor site to other parts of the breast or body; it is the most advanced stage
of breast cancer (stage four).^5,6 Metastatic breast cancer may be diagnosed
as an initial diagnosis, as a distant recurrence after treatment of early
breast cancer, or as a progression of earlier stage disease.^7,8 There is no
cure for metastatic breast cancer; the goal of treatment is to delay the
progression of the cancer.^5

About AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business with a
primary focus on the discovery, development and commercialization of
prescription medicines for gastrointestinal, cardiovascular, neuroscience,
respiratory and inflammation, oncology and infectious disease. AstraZeneca
operates in over 100 countries and its innovative medicines are used by
millions of patients worldwide.

For more information about AstraZeneca in the United States or our AZ&Me™
Prescription Savings programs, please visit www.astrazeneca-us.com or call
1-800-AZandMe (292-6363).

_________________________
     Di Leo A, Jerusalem G, Petruzelka L, et al. Results of the CONFIRM Phase
^1  III Trial comparing fulvestrant 250 mg with fulvestrant 500 mg in
     postmenopausal women with estrogen receptor–positive advanced breast
     cancer. J Clin Oncol. 2010;28(30):4594-4600.
     Di Leo A, Jerusalem G, Petruzelka L, et al., Final analysis of overall
^2   survival for the Phase III CONFIRM trial: fulvestrant 500 mg versus 250
     mg. Oral presentation # S1-4 presented at the 35^th San Antonio Breast
     Cancer Symposium, 5 December 2012.
^3   Prescribing Information for FASLODEX. AstraZeneca Pharmaceuticals LP,
     Wilmington, DE.
     Ferlay J et al. GLOBOCAN 2008, Cancer Incidence and Mortality Worldwide:
^4   IARC Cancer Base No. 10 [Internet]. Lyon, France, International Agency
     for Research on Cancer, 2010 Available online. Last accessed October 23,
     2012.
^5   National Cancer Institute. Treatment Option Overview, Patient Version.
     Available online. Last accessed July 26, 2012.
^6   National Cancer Institute. Metastatic Cancer: Questions and Answers.
     Available online. Last accessed July 26, 2012.
     Dawood S, Broglio K, Ensor J, Hortobagyi GN, Giordano SH. Survival
^7   differences among women with de novo stage IV and relapsed breast cancer.
     Annals Oncol. 2010;21:2169-2174.
     American Cancer Society. Treatment of invasive breast cancer, by stage.
^8   Last revised: August 23, 2012. Available Online. Last accessed September
     17, 2012.
     

                                                    2232405 Last Updated 12/12

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