September 17, 2010 — The US Food and Drug Administration (FDA) has approved a 500-mg dose of fulvestrant intramuscular injection (Faslodex; AstraZeneca) for the treatment of hormone receptor–positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy.
"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, MD, medical director for AstraZeneca, in a company news release. "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."
FDA approval was based on data from the phase 3, randomized, double-blind, multicenter COmparisoN of Faslodex In Recurrent or Metastatic breast cancer (CONFIRM) trial of 736 postmenopausal women (median age, 61.0 years) with advanced breast cancer who had disease recurrence on or after adjuvant endocrine therapy or progression after endocrine therapy for advanced disease.
Results showed that use of 500 mg fulvestrant significantly decreased the risk for disease progression by 20% compared with the 250-mg dose (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.68 - 0.94; P = .006), increasing median progression-free survival by 1.1 months (6.5 months vs 5.4 months, also significant to the P = .006 level).
Objective response rates calculated in patients with measurable disease did not differ significantly between the 500-mg and 250-mg fulvestrant groups (13.8% vs 14.6%; HR, 0.94; 95% CI, 0.57 - 1.55; P = .795). Although the numerical advantage in overall survival did not achieve statistical significance (25.1 months vs 22.8 months; HR, 0.84; 95% CI, 0.69 - 1.03; P = .091), a second survival analysis is planned for when approximately 75% of patients have had an event.
Study safety data showed that adverse events occurred with similar incidence and severity for patients receiving 500 mg and 250 mg fulvestrant, and most commonly included injection site pain (11.6% vs 9.1%), nausea (9.7% vs 13.6%), and bone pain (9.4% vs 7.5%). Pooled safety data showed that 15% of patients overall experienced postbaseline increases of 1 chemotherapy toxicity criteria grade or higher in liver enzymes; the incidence and severity of these elevations did not differ significantly between the 2 treatment groups.
The 500-mg dose of fulvestrant should be administered intramuscularly into the buttocks as two 250-mg (5-mL) injections — 1 in each buttock, given over 1 to 2 minutes, on days 1, 15, and 29, and then once monthly thereafter.
Fulvestrant therapy is contraindicated in patients with known hypersensitivity to the drug or product components. Hypersensitivity reactions, including urticaria and angioedema, have been reported in association with its use.
As with other intramuscular injections, caution is advised when treating patients with bleeding disorders or thrombocytopenia, and those receiving treatment with anticoagulants such as warfarin.
Because of the increased risk for drug exposure and toxicity, patients with moderate hepatic impairment should not receive fulvestrant doses higher than 250 mg; use in severe hepatic impairment has not been studied.
Fulvestrant can cause fetal harm when administered to pregnant women; fetal loss or abnormalities have been observed in animals administered fulvestrant at doses significantly smaller than the corresponding maximal human dose. Women of childbearing potential should be advised not to become pregnant while receiving treatment.
According to the news release, fulvestrant will be supplied as two 250-mg/5-mL vials, packaged together, early in the fourth quarter of 2010.
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Cite this: FDA Approves High-Dose Fulvestrant for Refractory Metastatic Breast Cancer - Medscape - Sep 17, 2010.