Approval based on Phase III study showing 500mg dose improved progression free survival over 250mg dose, with a comparable safety and tolerability profile
WILMINGTON, Del., Sept. 10 /PRNewswire-FirstCall/ -- AstraZeneca (NYSE: AZN) today announced that the U.S. Food and Drug Administration (FDA) has approved the 500mg dose of FASLODEX® (fulvestrant) Injection, replacing the previously approved monthly dose of 250mg, for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy.(1) The FDA approval of FASLODEX 500mg was based on results from CONFIRM (COmparisoN of FASLODEX In Recurrent or Metastatic breast cancer), a Phase III study which demonstrated that FASLODEX 500mg significantly reduced the risk of disease progression in patients with metastatic breast cancer, when compared with the 250mg dose. Safety and tolerability profiles of both doses were comparable.(2)
"This approval is an important advancement for women with metastatic breast cancer, where the treatment approach is centered on delaying disease progression," said Gershon Locker, M.D., Medical Director for AstraZeneca. "FASLODEX at 250mg has been an important treatment option for many women, and we now have data to show that the new 500mg dosing regimen can improve progression free survival compared with the 250mg dose."
The recommended dose of FASLODEX 500mg should be administered intramuscularly into the buttocks as two 250mg injections, one in each buttock, on days 1, 15, 29 and once monthly thereafter. A dose of 250mg is recommended in patients with moderate hepatic impairment.(1)
FASLODEX 500mg will be supplied as 2 x 250mg/5mL packaged together in early fourth quarter 2010. During this time, FASLODEX 250mg will still be available.
According to data from the U.S. National Cancer Institute, more than 207,000 American women will be diagnosed with breast cancer in 2010.(3) Approximately 155,000 women in the United States are currently living with metastatic breast cancer, and this number is projected to increase to nearly 162,000 by the year 2011.(4)
The CONFIRM study, presented for the first time at the annual San Antonio Breast Cancer Symposium (SABCS) in December 2009, showed FASLODEX 500mg reduced the risk of disease progression (assessed as progression free survival) by 20 percent (HR 0.80; 95% CI 0.68-0.94, p=0.006) when compared with FASLODEX 250mg. FASLODEX 500mg significantly increased median progression free survival to 6.5 months vs. 5.4 months with 250mg (p=0.006).
Objective Response Rates calculated in patients with measurable disease was not significantly different between FASLODEX 500mg (13.8%) and 250mg (14.6%) (HR=0.94; 95% CI: 0.57-1.55) (p=0.795). Median overall survival was 25.1 months with FASLODEX 500mg and 22.8 months with 250mg (HR=0.84; 95% CI: 0.69-1.03) (p=0.091). At the time of analysis, overall survival was not statistically significant. A pre-planned second survival analysis will occur as data mature when approximately 75% of patients have had an event.
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.
Approved Use For FASLODEX
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. If you have any questions concerning FASLODEX, please contact AstraZeneca Information Center at 1-800-236-9933, open Monday to Friday from 8 AM to 6 PM, excluding holidays.
CONFIRM (COmparisoN of FASLODEX In Recurrent or Metastatic breast cancer) was a Phase III, randomized, double-blind, parallel-group, multi-center trial comparing fulvestrant 500 mg (n=362) and 250 mg (n=374) in postmenopausal women with estrogen receptor-positive advanced breast cancer, who progressed or recurred following one prior endocrine therapy (antiestrogen or aromatase inhibitor). Eligible patients were randomized 1:1 to fulvestrant 500mg or 250mg, 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 clinical benefit (DoCB), overall survival and quality of life (QoL). Safety and tolerability were also assessed.
AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialization of prescription medicines. As a leader in gastrointestinal, cardiovascular, neuroscience, respiratory and inflammation, oncology and infectious disease medicines, AstraZeneca generated global revenues of $32.8 billion in 2009. In the United States, AstraZeneca is a $14.8 billion healthcare business.
For more information about AstraZeneca in the US or our AZ&Me™ Prescription Savings programs, please visit www.astrazeneca-us.com or call 1-800-AZandMe (292-6363).
(1) FASLODEX Prescribing Information.
(2) Di Leo A, Jerusalem G, Petruzelka L et al. CONFIRM: Phase III, randomized, parallel-group trial comparing fulvestrant 250 mg vs fulvestrant 500 mg in postmenopausal women with oestrogen receptor-positive advanced breast cancer. San Antonio Breast Cancer Symposium 2009. Abstract 25.
(3) National Cancer Institute. Surveillance Epidemiology and End Results cancer statistics. Web site: http://seer.cancer.gov/statfacts/html/breast.html. Accessed August 10, 2010.
(4) Data on File, 266478. AZPLP. Wilmington, DE.