Fulvestrant May Be FIRST for Hormone Receptor-Positive Advanced Breast Cancer

Fulvestrant may improve overall survival in patients with advanced, hormone receptor-positive breast cancer compared with anastrozole

medwireNews: Results from the FIRST phase II trial suggest that fulvestrant is superior to anastrozole for the first-line treatment of women with hormone receptor-positive locally advanced or metastatic breast cancer.

Median overall survival (OS) was 54.1 months for the 102 patients randomly assigned to receive open-label fulvestrant (500 mg on days 0, 14 and 28 followed by repeat doses every 28 days) compared with 48.4 months for the 103 patients given anastrozole 1 mg/day, giving a hazard ratio (HR) of 0.70.

The analysis, which was performed in July 2014 after 66.8% of study participants had died, suggests that the OS benefit with fulvestrant is consistent across patient subgroups stratified by characteristics including age, hormone receptor status and visceral disease.

Severe adverse events occurred in a similar number of fulvestrant- and anastrozole-treated patients, affecting 23.8% and 21.4%, respectively.

The findings were reported at the San Antonio Breast Cancer Symposium in Texas, USA, by John Robertson, from the University of Nottingham in the UK.

“This is an exciting and a promising finding given that CONFIRM, our earlier phase III trial to test 500 mg fulvestrant in a second-line setting, also showed a survival advantage over anastrozole,” he commented in a press release.

However, John Robertson cautioned: “Despite the improved disease control on treatment and improved overall survival seen in the FIRST study, we do not expect this to change the standard of care at this point since it was a phase II study.

“A phase III [FALCON] study has been initiated to support the regulatory approval for fulvestrant as a first-line agent in this setting, which would be practice-changing.”

In other news reported at the San Antonio Breast Cancer Symposium, the BOLERO-1 trial showed no significant gain in progression-free survival (PFS) with the addition of everolimus to treatment regimens for HER2-positive advanced breast cancer.

The final analysis of the phase III study of 719 patients was performed after a median of 41.3 months and after 425 patients had experienced disease progression.

Patients randomly assigned to receive everolimus alongside trastuzumab plus paclitaxel had a median PFS of 15.0 versus 14.5 months for those randomly assigned to receive placebo with trastuzumab and paclitaxel.

However, among a hormone receptor-negative patient subgroup, there was a “clinically relevant” 7.2-month gain in PFS with everolimus compared with placebo, at 20.3 versus 13.1 months and a HR of 0.66.

This “just fell short of crossing the protocol pre-specified level of statistical significance”, reported presenting author Sara Hurvitz, from the University of California, Los Angeles, USA.

Thus, everolimus “may have a role in this patient subpopulation”, the researchers believe.

The BOLERO-1 study did not show any new safety signals for everolimus, they add, with 21.8% of patients having a severe adverse event compared with 7.6% of controls. Adverse event-related deaths during treatment were reported for 3.6% and 0.0% of patients, respectively.

However, the researchers note that all but one of the everolimus adverse event-related deaths occurred in the first 15 months of the study - after an aggressive management strategy for side effects was introduced, there was just one further death.

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