Increasing the dose of fulvestrant (Faslodex) from 250 mg to 500 mg yielded a longer median overall survival as well as a lower overall risk of death in women with locally advanced or metastatic estrogen receptor (ER)-positive breast cancer, according to results from the CONFIRM trial presented at the San Antonio Breast Cancer Symposium (SABCS).
“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 Angelo Di Leo, MD, PhD, of the department of medical oncology at the Hospital of Prato, Istituto Toscano Tumori in Prato, Italy. “Our results indicate that this should be modified to a 500 mg dose.”
The CONFIRM trial included 736 women in 17 countries; 362 received a 500 mg dose of fulvestrant and 374 received 250 mg. They were followed until 75% had died; for the present analysis, 554 of the patients had died, 63 were lost to follow-up, and 16 withdrew consent. The primary endpoint was progression-free survival (PFS); the median PFS for the 500 mg patients was 6.5 months compared with 5.5 months in the 250 mg group, for a hazard ratio of 0.80 (95% CI, 0.68–0.94; P = .006).
Overall survival was also better with the higher dose. The median time to death in the 500 mg group was 26.4 months vs 22.3 months for the 250 mg patients.
The increased dose did not appear to have any significant effect on toxicity of the drug. A total of 35 patients in the 500 mg dose group (9.7%) had any serious adverse event, compared with 27 patients (7.2%) in the lower dose group.
“Of note, the improvement in survival with the higher dose of fulvestrant was achieved without increasing treatment toxicity,” Di Leo said in a press release. “Indeed, the dose of 500 mg had the same toxicity profile as the 250 mg dose.” He also noted that next steps include studying 500 mg fulvestrant in combination with other agents such as PI3K inhibitors or anti-HER2 agents.
CONFIRM was a randomized, double-blind, parallel-group, multicenter phase III trial of women who recurred or progressed following endocrine therapy. Fulvestrant was given as either one or two 250 mg intramuscular injections; the 250 mg group received a second injection of placebo. Patients received treatment at days 0, 14, 28, and every 28 days thereafter.