Final Overall Survival Analysis of CONFIRM Trial Shows Advantage of Higher Dose of Fulvestrant in Advanced Breast Cancer
As reported in the Journal of the National Cancer Institute by Di Leo et al, the final overall survival analysis of the CONFIRM trial has shown a significant benefit of fulvestrant (Faslodex) at 500 mg vs 250 mg in postmenopausal women with locally advanced or metastatic estrogen receptor–positive breast cancer recurring or progressing after prior endocrine therapy.
Study Details
The initial results of CONFIRM showed that the 500-mg dose was associated with significantly better progression-free survival, resulting in approval of the 500-mg dose. At the time of that analysis, approximately 50% of patients had died, with the 500-mg dose being associated with a trend toward improved overall survival. At that time, a final analysis was planned when 75% of patients had died.
In the double-blind trial, 736 women were randomly assigned to 500 mg of fulvestrant given as two 5-mL intramuscular injections on days 0, 14, and 28 and every 28 days thereafter (n = 362) or 250 mg of fulvestrant administered as one 5-mL injection of fulvestrant at 250 mg and one placebo injection on days 0, 14 (two placebo injections only), and 28 and every 28 days thereafter (n = 374). Patients had a median age of 61 years. Overall survival was analyzed using an unadjusted log-rank test.
Improved Overall Survival
At the initial analysis, median overall survival was 25.1 months in the 500-mg group vs 22.8 months in the 250-mg group (hazard ratio [HR] = 0.84, P = .09). In this final analysis, after 75.3% of patients had died, median overall survival was 26.4 months in the 500-mg group vs 22.3 months in the 250-mg group (HR = 0.81, nominal P = .02).
Among 230 patients in the 500-mg group and 239 in the 250-mg group for whom information on first subsequent therapy after progression was available, 59% of both groups received chemotherapy and 35% and 31% received endocrine therapy; 2% of the 250-mg group crossed over to 500-mg treatment. Best responses to subsequent therapy were complete response in 1% of the 500-mg group and 0% of the 250-mg group, partial response in 7% and 8%, and stable disease in 25% and 32%.
No New Safety Concerns
No new safety concerns were identified during additional follow-up. During the entire treatment period, 10% of 500-mg recipients and 7% of 250-mg recipients had a serious adverse event, with death due to serious adverse events occurring in 1.4% and 1.9% of patients. There were no clinically important differences in serious adverse event profiles between the two groups and no clustering of serious adverse events was observed in either group.
The investigators concluded, “In patients with locally advanced or metastatic estrogen receptor-positive breast cancer, fulvestrant 500 mg is associated with a 19% reduction in risk of death and a 4.1-month difference in median [overall survival] compared with fulvestrant 250 mg. Fulvestrant 500 mg was well tolerated, and no new safety concerns were identified.”
Angelo Di Leo, MD, PhD, Hospital of Prato, Italy, is the corresponding author for the Journal of the National Cancer Institute article.
The study was designed and funded by AstraZeneca Pharmaceuticals. For full disclosures of the study authors, visit jnci.oxfordjournals.org.
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