Among patients with locally advanced or metastatic estrogen receptor–positive breast cancer, fulvestrant (Faslodex) given at 500 mg “is associated with a 19% reduction in risk of death and a 4.1-month difference in median overall survival compared with fulvestrant 250 mg,” according to final results of the phase III CONFIRM (Comparison of Faslodex in Recurrent or Metastatic Breast Cancer) trial.
A total of 736 women from 128 centers in 17 countries participated. The median age was 61 years. “Patients were randomly assigned 1:1 to fulvestrant 500 mg administered as two 5-mL intramuscular injections on days 0, 14, and 28 and every 28 (±3) days thereafter or fulvestrant 250 mg administered as two 5-mL intramuscular injections (one fulvestrant and one placebo [identical in appearance to study drug]) on days 0, 14 (two placebo injections only), and 28 and every 28 (±3) days thereafter,” Angelo Di Leo, MD, PhD, of the Sandro Pitigliani Medical Oncology Unit in Prato, Italy, and colleagues explained in the Journal of the National Cancer Institute.
The primary study endpoint was progression-free survival, and the initial results showed that the 500-mg dose of fulvestrant was associated with a statistically significant increase in progression-free survival compared to the 250-mg dose. “Based on these data, the 500-mg dose of fulvestrant is now the approved dose in the European Union (approved in March 2010), United States (approved in September 2010), Japan (approved in November 2011), and other countries worldwide,” the researchers noted.
At the time of the initial analysis, approximately 50% of patients had died. “A final analysis of [overall survival] was subsequentially planned for when 75% of patients had died,” the authors stated. “At the final survival analysis, 554 of 736 (75.3%) patients had died. Median [overall survival] was 26.4 months for fulvestrant 500 mg and 22.3 months for 250 mg (hazard ratio = 0.81; 95% confidence interval = 0.69–0.96; nominal P = .02),” the researchers reported.
Throughout the entire treatment period, 35 patients (9.7%) in the fulvestrant 500-mg group and 27 patients (7.2%) in the fulvestrant 250-mg group had serious adverse events. “[Serious adverse events] that were causally related to study treatment were reported for eight (2.2%) and four (1.1%) patients, and [serious adverse events] with an outcome of death were reported for five (1.4%) and seven (1.9%) patients in the fulvestrant 500-mg and fulvestrant 250-mg groups, respectively,” the investigators stated.
“The results of this study raise a number of questions that need to be addressed in future trials,” the authors noted. These questions include whether fulvestrant 500 mg might be a better option than aromatase inhibitors as first-line treatment for postmenopausal women with estrogen receptor–positive advanced breast cancer and whether fulvestrant should be part of a polyendocrine therapy approach.
Based on the CONFIRM trial’s progression-free and overall survival results, the investigators stated that whenever fulvestrant treatment is necessary, it should be initiated at the dose of 500 mg. ■
DiLeo A, et al: J Natl Cancer Inst 106(1):djt337, 2014.