Higher Dose of Fulvestrant Associated With Improved Survival in Advanced Breast Cancer

Ben Leach
Published: Wednesday, Dec 05, 2012

Dr. Angelo Di Leo

Photo Courtesy © SABCS/Todd Buchanan 2012

Angelo Di Leo, MD, PhD
Postmenopausal women with advanced estrogen receptor (ER)–positive breast cancer lived longer when they received a 500-mg dose of fulvestrant (Faslodex) as compared with a 250-mg dose, according to the final analysis of the phase III CONFIRM trial. The data were presented at the 35th San Antonio Breast Cancer Symposium.

The results of a primary analysis of this trial were published in the Journal of Clinical Oncology in 2010 and demonstrated a trend toward improved overall survival (OS) when patients received 500 mg of fulvestrant compared with 250 mg. However, those results were not final and did not achieve statistical significance. The first analysis was done at 50% maturity, meaning that 50% of patients in the study had died during follow-up.

“Based on these encouraging results, we decided to perform a second survival analysis to be done when 75% of patients had died,” said Angelo Di Leo, MD, PhD, head of the department of Medical Oncology at the Hospital of Prato, Instituto Toscano Tumori in Prato, Italy, and lead author of the study.

In the CONFIRM trial, 736 women with locally advanced or metastatic ER-positive disease were randomized to receive either 500 mg of fulvestrant (intramuscular; days 0, 14, and 28, and every 28 days thereafter; n = 362) or 250 mg of fulvestrant (intramuscularly; every 28 days; n = 374). The trial was placebo-controlled, so patients in the 250 mg arm also received 1 placebo injection on days 0 and 28 and two placebo injections on day 14. After the primary analysis, patients in the 250 mg arm were allowed to switch to the 500 mg dose. All patients were followed up for OS, even if they discontinued treatment, unless consent was withdrawn.

The final analysis found that median OS in the 500-mg fulvestrant arm was 26.4 months compared with 22.3 months in the 250-mg fulvestrant arm (hazard ratio = 0.81; 95% CI, 0.69-0.96; nominal P = .016). During treatment and follow-up, 35 patients (9.7%) in the 500-mg fulvestrant arm experienced at least one serious adverse event (SAE), compared with 27 patients (7.2%) in the 250-mg fulvestrant group. The study found that an SAE leading to death occurred in 5 patients (1.4%) in the 500-mg fulvestrant arm compared with 6 patients (1.6%) in the 250-mg fulvestrant arm.

While the OS in this trial did reach statistical significance, Di Leo noted that it is a nominal P value because this was an exploratory analysis that did not have enough statistical power to detect the true statistical significance of the study when comparing the two arms. However, between the primary and final analyses, Di Leo said there is a clear trend toward improved survival.

“I think that it is interesting to highlight the concept that the two survival analyses are perfectly consistent,” Di Leo said. “They are leading to the same conclusion, and that conclusion is that there is an increased benefit in terms of survival for patients who receive 500 mg of fulvestrant.”


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. Presented at: 2012 CTRC-AACR San Antonio Breast Cancer Symposium; December 4-8, 2012; San Antonio, Texas. Abstract S1-4.

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