Fulvestrant improved overall survival compared with anastrozole, among women with treatment-naive, advanced, hormone receptor-positive breast cancer.
Fulvestrant 500 mg significantly improved overall survival compared with anastrozole, among women with treatment-naive, advanced, hormone receptor-positive breast cancer, according to data from the phase II FIRST trial presented at the 2014 San Antonio Breast Cancer Symposium (SABCS).
“This is now the second randomized controlled trial where fulvestrant 500 mg has shown a time-to-progression and survival advantage over the control arm,” said study presenter John Robertson, MD, professor of surgery, University of Nottingham, Royal Derby Hospital, United Kingdom.
The phase III CONFIRM study found fulvestrant 500 mg to have a survival advantage over anastrozole in the second-line setting.
According to Robertson, fulvestrant was originally developed in a 250 mg dosage. However, early trials of fulvestrant 250 mg in the first and second line showed only equivalence to anastrozole and similarity to tamoxifen. However, when it was decided to double the dose, and the CONFIRM study showed a survival advantage for fulvestrant 500 mg, the researchers decided to also look at outcomes with the higher dose in the first-line setting.
The FIRST trial randomly assigned 200 patients to fulvestrant 500 mg or anastrozole 1 mg. The primary endpoint of the study was clinical benefit rate. The secondary endpoint was time to progression.
There was no significant difference in clinical benefit rate found between patients assigned fulvestrant (72.5%) and those assigned anastrozole (67%), but the results did indicate that fulvestrant was equivalent to anastrozole.
Looking at time to progression, however, patients assigned fulvestrant had a 34% reduction in progression compared with anastrozole (HR = 0.66; 95% CI, 0.47-0.92). The median time to progression was 23.4 months for fulvestrant and 13.1 months for anastrozole.
The researchers also conducted an overall survival analysis, which was added to the protocol as an amendment after the original protocol was developed. At the time of the analysis, 22.5% of patients in the fulvestrant arm and 9.7% in the anastrozole arm were still alive.
Patients assigned fulvestrant survived a median of 54.1 months compared with 48.4 months for anastrozole. Fulvestrant was associated with a 30% reduction in death (HR = 0.70; 95% CI, 0.50-0.98). In addition, the survival benefit appeared to be consistent across all of the predefined subgroups.
1. Robertson JFR, Llombart-Cussac A, Feltl D, et al. Fulvestrant 500 mg versus anastrozole as first-line treatment for advanced breast cancer: Overall survival from the phase II “first” study. Presented at 2014 San Antonio Breast Cancer Symposium; December 9-13, 2014; San Antonio, Texas. Abstract S6-04.