Women with untreated advanced breast cancer had a trend toward greater clinical benefit with fulvestrant (Faslodex) versus anastrozole (Arimidex) as first-line hormonal therapy, according to results from the FIRST (Fulvestrant First-Line Study Comparing Endocrine Treatments) randomized trial (Table
). The clinical benefit rate (CBR) was 72.5% for patients treated with fulvestrant compared with 67% for patients taking anastrozole. This translated to a 30% increase in the odds for clinical benefit, which did not reach statistical significance (P
= .386). Fulvestrant was associated with a 36% reduction in the hazard for progression, however, which was significantly better than anastrozole (P
"The time-to- progression benefit for fulvestrant was consistent in all predefined subgroups," said James F. R. Robertson, MD, a breast oncologist at the University of Nottingham in England. "Patients who progress on either fulvestrant or anastrozole remain sensitive to subsequent endocrine treatments." Earlier trials evaluated a 250-mg dose of fulvestrant as second-line endocrine therapy, which failed to slow breast cancer progression compared with anastrozole or tamoxifen, said Robertson. A recent randomized trial, however, found that a 500-mg dose of fulvestrant was associated with significant improvement in progression-free survival compared with 250 mg of fulvestrant as second-line endocrine therapy (J Clin Oncol
. 2010;28:4594- 4600).
Those results led to a randomized, open-label comparison of a 500-mg dose of fulvestrant with a 1-mg dose of anastrozole as first-line endocrine therapy for postmenopausal women (N = 205) with advanced, estrogen receptor-positive breast cancer. The primary endpoint was CBR (objective response plus prolonged stable disease); secondary endpoints included objective response rate, time to progression, duration of response, duration of clinical benefit, and safety.
The first planned analysis occurred after a median follow-up of 8.0 months in the fulvestrant arm and 5.9 months in the anastrozole arm, at which point 36% of patients had progressed. The analysis also showed a disparity in progression between the groups: 29.4% taking fulvestrant progressed compared with 41.7% given anastrozole (P
An updated analysis, performed after a median follow-up of 19 months in the fulvestrant arm and 13 months in the anastrozole group, showed that 69% of patients had progressed. The disparity in rates of progression between the groups that was reported in the first analysis persisted, with a 61.8% rate of progression for the fulvestrant arm compared with a 76.7% rate of progression for the anastrozole group; this translates to a 34% difference in the hazard for progression favoring fulvestrant (P
= .01). The median time to progression was 23.4 months for patients treated with fulvestrant compared with 13.1 months for patients taking anastrozole. Adjustment for predefined covariates resulted in a hazard ratio of 0.64 and a 36% reduction in favor of fulvestrant, identical to the advantage shown in the first analysis.
Robertson said 34 patients in the fulvestrant arm and 50 in the anastrozole arm who progressed received additional hormonal therapy, which benefitted several patients. Of these women, 14 (41.2%) from the fulvestrant group and 21 (42%) from the anastrozole arm had an objective response or stable disease for >/=24 weeks.
The safety analysis showed no significant differences between the treatment groups for any prespecified adverse events. Additionally, 14 patients (7 in each group) experienced a cumulative 22 serious adverse events.
The results of the study compare favorably with other published phase III randomized trials of aromatase inhibitors versus tamoxifen as first-line endocrine therapy, said Robertson. In one study, anastrozole resulted in a time to progression of 8.5 months, an overall response rate of 29%, and a CBR of 57.1% (Cancer
. 2001;92:2247-2258). A similar study involving letrozole (Femara) showed a time to progression of 9.4 months, a response rate of 30.2%, and a CBR of 48.8% (J Clin Oncol
. 2001;19:2596- 2606). Abstract S1-3
_____________________________________________Robertson JFR, Lindemann JPO, Llombart-Cussac A, et al. A comparison of fulvestrant 500-mg with anastrozole as first-line treatment for advanced breast cancer: Followup analysis from the FIRST study. Paper presented at: San Antonio Breast Cancer Symposium; December 8-12, 2010; San Antonio, TX.