(ChemotherapyAdvisor) – Fulvestrant 500mg is associated with a clinically relevant 4.1-month difference in median overall survival (OS) and a 19% reduction in risk of death vs fulvestrant 250mg in postmenopausal women with locally advanced or metastatic estrogen-receptor (ER)–positive breast cancer.

That’s the conclusion of final analysis of OS data from the randomized phase 3 COmparisoN of Faslodex In Recurrent or Metastatic breast cancer (CONFIRM) trial presented during the 2012 CTRC-AACR San Antonio Breast Cancer Symposium.

“Of note, the improvement in survival with the higher dose of fulvestrant was achieved without increasing treatment toxicity. Indeed, the dose of 500mg had the same toxicity profile as the 250mg dose,” said Angelo Di Leo, MD, PhD, head of the department of medical oncology at the Hospital of Prato, Istituto Toscano Tumori in Prato, Italy.

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The double-blind, parallel-group, multicenter study randomly assigned 736 women from 128 centers in 17 countries to 500mg intramuscularly (IM) on days 0, 14 and 28, every 28 days (n=362), or fulvestrant 250mg IM every 28 days (n=374) between February 2005 and August 2007. Mean age was 61.0 years.

At the time of the primary analysis, fulvestrant 500mg was associated with a significant increase in progression-free survival (PFS) vs the lower dose, and about 50% of patients had died. Median overall survival (OS) was 25.1 months for fulvestrant 500mg and 22.8 months for fulvestrant 250mg (HR 0.84; 95% CI 0.69–1.03; P=0.091).

After the primary analysis, patients on fulvestrant 250mg were permitted to switch to 500mg and 8 patients (2.1%) did so. At follow-up analysis, 103 patients (14.0%) continued in the trial, 21 (2.9%) on treatment and 82 (11.1%) not on treatment; 554 patients (75.3%) had died.

Median OS was 26.4 months for fulvestrant 500mg and 22.3 months for fulvestrant 250mg (HR 0.81; 95% CI, 0.69–0.96; nominal P=0.016).

During the treatment period, 32 patients (8.9%) had at least one serious adverse event (SAE) in the fulvestrant 500mg arm and 25 patients (6.7%) in the fulvestrant 250mg arm; those related to study treatment were reported for 6 (1.7%) and 3 (0.8%) patients, respectively. Five patients (1.4%) in the fulvestrant 500mg arm died, as did 6 (1.6%) in the fulvestrant 250mg arm.

“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 250mg dose,” said Di Leo. “Our results indicate that this should be modified to a 500mg dose.”

The investigators will next study fulvestrant 500mg in combination with biological agents, such as PI3K inhibitors or anti-HER2 agent, that can reverse resistance to endocrine therapy, an approach that “could further increase the activity of fulvestrant given at the 500mg dose,” he concluded.

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