High-Dose Fulvestrant Leads to Better Breast Cancer Survival

SAN ANTONIO, Texas — A double dose of fulvestrant (Faslodex, AstraZeneca) is associated with better survival than a standard dose in the treatment of postmenopausal women with advanced estrogen-receptor (ER)-positive breast cancer, according to updated results from the phase 3 Comparison of Faslodex in Recurrent or Metastatic Breast Cancer (CONFIRM) trial.

On the basis of these results, when a clinician is planning to use fulvestrant to treat menopausal women with ER-positive advanced breast cancer, "the dose of 500 mg should be considered and recommended," lead investigator Angelo Di Leo, MD, PhD, reported here at the 35th Annual San Antonio Breast Cancer Symposium.

The results update and strengthen previously published findings from the CONFIRM study (J Clin Oncol. 2010;28:4594-4600), which showed a progression-free survival benefit with the higher dose at a point when 50% of study subjects had died (hazard ratio [HR], 0.80; P = .006).

Overall survival at this time point was not statistically better (P = .091), said Dr. Di Leo, who is head of the Department of Medical Oncology at the Hospital of Prato, Istituto Toscano Tumori, in Italy.

The updated secondary survival analysis, performed at the study's 75% maturity rate, shows a median overall survival benefit with the high dose (HR, 0.81) that has "nominal" statistical significance (P = .016), he reported.

The P value is nominal because "this was an exploratory analysis and we didn't have enough statistical power to perform a formal statistically validated analysis comparing the 2 study arms," he explained during a press conference.

The CONFIRM study involved 736 women (median age, 61 years) with locally advanced or metastatic ER-positive breast cancer that had recurred or progressed after endocrine therapy.

From February 2005 to August 2007, women from 128 centers in 17 countries were randomized to intramuscular (IM) fulvestrant 500 mg (n = 362) or 250 mg (n = 374) on days 0, 14, and 28, and every 28 days thereafter.

Women in the 500 mg group received two 250 mg IM fulvestrant injections; women in the 250 mg group received 1 250 mg IM fulvestrant injection and 1 IM placebo injection.

The researchers found the higher dose was "associated with a 4-month increase in median overall survival and a 19% reduction in the risk of death" (26.4 vs 22.3 months), said Dr. Di Leo.

Additionally, the safety results "do no support any clinically relevant difference between the doses," he said.

Eight serious adverse events were deemed to be causally related to fulvestrant in the high-dose group, as were 4 in the low-dose group.

Asked to comment on the findings, Deb Fletcher, PharmD, BCOP, a pharmacist at the Huntsman Cancer Institute, University of Utah, in Salt Lake City, told Medscape Medical News that the study protocol initially involved a single 500 mg IM injection, rather than 2 injections of 250 mg.

Some of the smaller women found this to be painful. "It's a large volume and some of our ladies don't have a lot of muscle, especially if they're petite and metastatic," she said.

The study was funded by AstraZeneca. Dr. Di Leo reports being a consultant for Novartis. Coauthor Guy Jerusalem reports receiving grant/research support from AstraZeneca. Coauthors Sally Garnett and Yuri Rukazenkov report being employees of AstraZeneca. Coauthor Miguel Martin reports being a consultant for AstraZeneca and Pfizer.

35th Annual San Antonio Breast Cancer Symposium (SABCS): Abstract S1-4. Presented December 5, 2012.