The initial evidence for fulvestrant comes from two Phase III clinical trials (Trials 0020 and 0021) involving a total of 851 patients with locally advanced or metastatic hormone-receptor breast cancer who had progressed on prior endocrine therapy, primarily tamoxifen. The women were randomised to receive fulvestrant 250 mg IM monthly or anastrozole 1 mg PO daily. The primary endpoint was overall survival to determine non-inferiority for fulvestrant.r
The EFECT Phase III trial compared the use of fulvestrant 250 mg IM given day 1, 14, 28 and every 28 days thereafter with exemestane 25 mg PO daily in post-menopausal women with locally advanced or metastatic breast cancer who had relapsed during or within 6 months of completion of adjuvant treatment or failed first line metastatic treatment with a non-steroidal aromatase inhibitor. A total of 639 women were accrued from August 2003 to November 2005. The primary endpoint of the study was time to disease progression.r
The CONFIRM Phase III trial involved 736 post-menopausal patients enrolled from February 2005 to August 2007 with locally advance or metastatic ER-positive breast cancer who had experienced a relapse on or within 1 year from completion of adjuvant endocrine therapy or who had failed first line endocrine treatment for metastatic disease. Patients were randomly assigned to fulvestrant 500 mg day 1, 14, 28 and every 28 days thereafter or fulvestrant 250 mg in the same schedule. The primary endpoint was progression free survival.r
Efficacy
In both the analysis of Trial 0020 and 0021 and the EFECT trial, fulvestrant 250 mg was shown to be at least as effective as anastrozole and exemestane respectively.r,r In the analysis of Trial 0020 and 0021, the overall survival was 27.4 months in the fulvestrant group compared with 27.7 in the anastrozole group.r In EFECT, the time to disease progression was 3.7 months in both groups.r Fulvestrant 500 mg was shown to lead to a significant prolongation of progression free survival over 250 mg in CONFIRM, 6.5 months vs 5.5 months (HR = 0.80; 95% CI, 0.68-0.94; P = 0.006). There was no difference in the groups in overall response and clinical benefit rates, however a greater number of patients in the 500 mg group had stable disease compared with the 250 mg group.r
Kaplan-Meier analysis of Progression-free survivalr
© Journal of Clinical Oncology 2010
Toxicity
In EFECT and Trials 0020 and 0021, fulvestrant was as tolerable as exemestane and anastrozole respectively.r,r Joint symptoms were slightly less in all studies in the fulvestrant groups. In CONFIRM, there was no substantial difference in the incidence and severity of side effects in the 500 mg fulvestrant group compared with the 250 mg group. Serious adverse events were uncommon in both groups, however 1 patient died in the 500 mg group due to interstitial lung disease and 1 in the 250 mg due to cardiac failure resulting from hypertension.r
Toxicity r |
Fulvestrant %
(n=351) |
Exemestane %
(n=340) |
Injection-site pain |
9 |
8 |
Hot flashes |
9 |
12 |
Nausea |
7 |
8 |
Fatigue |
6 |
10 |
Myalgia |
4 |
4 |
Arthralgia |
4 |
6 |
Diarrhoea |
3 |
3 |
Asthenia |
3 |
2 |
Injection-site reaction |
2 |
2 |
Alopecia |
2 |
2 |
Headache |
2 |
3 |
Anorexia |
2 |
2 |
Dyspepsia |
1 |
2 |
Pain in extremity |
0 |
2 |