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-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.