Increasing the dose of fulvestrant from 250 mg to 500 mg improved
median overall survival in women with locally advanced or metastatic estrogen receptorpositive breast cancer, according to updated data from the CONFIRM trial presented at
the 2012 CTRC-AACR San Antonio Breast Cancer Symposium.
The Comparison of Faslodex in Recurrent or Metastatic Breast Cancer (CONFIRM) trial
is a randomized, double-blind, parallel-group, multicenter, phase III trial of
postmenopausal women with estrogen receptor (ER)-positive advanced breast cancer that
recurred or progressed following endocrine therapy.
“Of note, the improvement in survival with the higher dose of fulvestrant was achieved
without increasing treatment toxicity. Indeed, the dose of 500 mg had the same toxicity
profile as the 250-mg dose,” said Angelo Di Leo, M.D., Ph.D., head of the department of
medical oncology at the Hospital of Prato, Istituto Toscano Tumori in Prato, Italy.
Between February 2005 and August 2007, researchers randomly assigned 736 women
from 128 centers in 17 countries to 250 mg or 500 mg of fulvestrant and followed them
until 75 percent of the patients died. At the time of analysis, 554 patients had died, 63
were lost to follow-up and 16 withdrew consent.
Among the entire study population, the 500-mg dose was associated with a clinically
relevant 4.1-month difference in median overall survival compared with the lower dose:
26.4 months in the 500-mg group and 22.3 months in the 250-mg group. Researchers also
saw a 19 percent reduction in risk for death in the 500-mg group compared with the 250-Higher Doses of Fulvestrant Prolonged Survival in Patients With Advanced Breast
Cancer
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mg group. Serious adverse events occurred in 8.9 percent of patients who had received
the 500-mg dose and in 6.7 percent of patients in the 250-mg group.
“For those postmenopausal women with recurrent or progressing ER-positive locally
advanced or metastatic breast cancer for whom fulvestrant is the appropriate treatment
choice, the standard of care is a 250-mg dose,” said Di Leo. “Our results indicate that this
should be modified to a 500-mg dose.”
According to Di Leo, the next research step will be to study 500 mg of fulvestrant in
combination with biological agents, such as PI3K inhibitors or anti-HER2 agents that can
reverse resistance to endocrine therapy.
“This approach could further increase the activity of fulvestrant given at the 500-mg
dose,” he said.
