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

WILMINGTON, Del.--(BUSINESS WIRE)--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).

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^1	Di Leo A, Jerusalem G, Petruzelka L, et al. Results of the CONFIRM Phase 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.
^2	Di Leo A, Jerusalem G, Petruzelka L, et al., Final analysis of overall 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.
^4	Ferlay J et al. GLOBOCAN 2008, Cancer Incidence and Mortality Worldwide: 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.
^7	Dawood S, Broglio K, Ensor J, Hortobagyi GN, Giordano SH. Survival differences among women with de novo stage IV and relapsed breast cancer. Annals Oncol. 2010;21:2169-2174.
^8	American Cancer Society. Treatment of invasive breast cancer, by stage. Last revised: August 23, 2012. Available Online. Last accessed September 17, 2012.

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