Findings from the CONFIRM clinical trial presented at the 2012 San Antonio Breast Cancer Symposium in December showed that increasing the dose of fulvestrant (Faslodex) from 250 mg to 500 mg for women with estrogen receptor-positive metastatic breast cancer increased median overall survival by 4.1 months. Overall survival is the time a person lives from the start of treatment until death from any cause.
Fulvestrant, a selective estrogen receptor downregulator, or SERD, blocks the body’s estrogen from helping cancer cells to grow in estrogen receptor-positive breast cancer. It is a type of hormonal therapy given only to postmenopausal women.
Fulvestrant was initially approved for the treatment of metastatic breast cancer at a dose of 250 mg/month after studies showed that it was as effective as anastrozole (Arimidex) in treating hormone-sensitive metastatic breast cancer that progressed on tamoxifen. After a loading (higher) dose and schedule, fulvestrant is usually given once a month by injection into muscle.
The trial explored whether raising the dose to 500 mg would be safe and effective. Early results of this trial were published several years ago. The current analysis reports on the final findings.
CONFIRM enrolled 736 postmenopausal women with estrogen receptor-positive metastatic or locally advanced disease that grew or spread after treatment with other hormonal therapies. They came from 17 countries and were enrolled between February 2005 and August 2007. The median age of participants was 61.
The women were randomly assigned to one of two research arms:
- Arm I participants received two 250 mg injections of fulvestrant
- Arm II participants received one 250 mg injection of fulvestrant and one 250 mg injection of a placebo, an inactive substance
Participants in both arms had injections on the first day of treatment, day 14 and day 28 (the loading dose and schedule), and then every 28 days from then on.
The women were followed until they withdrew from the study or died. After a preliminary data analysis that showed the benefit of the higher dose, women assigned to receive 250 mg were given the option to switch to 500 mg.
Participants in the 500 mg group lived an average of 4.1 months longer than those in the standard-treatment group, an increase in overall survival from 22.3 months to 26.4 months. This translates to a 19 percent lower risk of death for those in the 500 mg group versus those in the 250 mg group.
The risk of serious side effects was the same for both groups, meaning the increase in the fulvestrant dosage did not cause significantly more life-threatening side effects for participants.
What This Means For You
The investigators on this trial believe that increasing the standard dose of fulvestrant from 250 mg to 500 mg may increase the length of life for women with estrogen receptor-positive advanced breast cancer. Future research will combine the 500 mg dose with other medicines, such as anti-HER2 therapies or specific protein kinase inhibitors.
Some doctors believe this study, bolstered by earlier findings, could change the standard of care for fulvestrant to 500 mg over the current 250 mg. Though the higher dose of fulvestrant may not be immediately available, you may be able to access it through a clinical trial. Talk with your doctor about your interest in participating in future trials and your eligibility.
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. Publication #S1-4. San Antonio Breast Cancer Symposium: Dec. 5, 2012.