Faslodex approved for breast cancer.
With the introduction of Faslodex (fulvestrant injection, AstraZeneca), women with advanced breast cancer no longer responding to tamoxifen now have another option.
Last month, the Food & Drug Administration announced the approval of fulvestrant injection for the treatment of hormone receptor positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy.
Unlike the antiestrogen tamoxifenwhich blocks the estrogen receptorand the aromatase inhibitors, such as Arimidex (anastrozole, AstraZeneca)which reduce the amount of estrogen in the bodyfulvestrant exhibits its effect by targeting and downregulating the estrogen receptor. Due to this difference in mechanism of action, fulvestrant injection offers an additional approach to treating breast cancer and may help control resistant cases for longer periods of time.
The FDA based its approval on data from two phase III, randomized clinical trials comparing fulvestrant with anastrozole. The studies included 400 and 451 postmenopausal women with locally advanced or metastatic breast cancer in North America and Europe, respectively. All subjects had exhibited disease progression following treatment with an antiestrogen or progestin. Participants received either fulvestrant injection 250 mg intramuscularly once a month or anastrozole 1 mg orally once daily. Patients were initially randomized to a 125-mg-per-month dose of fulvestrant injection in both trials, but after very low response rates were seen, the low-dose groups were dropped.
Results showed that fulvestrant injection was at least as effective as anastrozole, with the tumor response rates at 17% for both drugs in the North American trial. In the European trial, fulvestrant injection produced a 20.3% response rate compared with 14.9% for the anastrozole group.
Time to progression of cancer in the North American trial was 165 days in the fulvestrant group versus 103 days for anastrozole, and 166 days versus 156 days in the European study. Mortality rates were 52.9% versus 47.4% in the North American trial and 56.3% versus 56.8% in Europe for fulvestrant and anastrozole, respectively. There are currently no efficacy data for the use of fulvestrant injection in premenopausal women with advanced breast cancer.
"It appears Faslodex will be used as an alternative to aromatase inhibitors in hormone receptor positive metastatic breast cancer patients who have failed tamoxifen therapy", said Brenna Brown, Pharm.D., BCOP, clinical oncology pharmacist at H. Lee Moffitt Cancer Center and Research Institute at the University of South Florida. Since both drugs appear to be equally efficacious in this setting, patient preference and compliance with oral medications will be the deciding factor, Brown noted. Drug cost may also play a role, she added, since treatment with fulvestrant injection may be as much as three to four times the cost of anastrozole.
Fulvestrant therapy may offer compliance benefits since treatment is normally given once a month as an intramuscular injection. However, due to its route of administration, fulvestrant is not recommended for individuals with bleeding disorders or thrombocytopenia, or for those receiving anticoagulant therapy.
Classified under pregnancy category D, fulvestrant injection is contraindicated in pregnant women because of the potential for fetal harm. Animal studies showed the drug crosses the placenta, causing fetal abnormalities and loss of pregnancy.
As a phase IV commitment to the FDA, AstraZeneca has agreed to monitor medication errors caused by potential name confusion with Zoladex (goserelin), its injectable prostate cancer drug.