SAN ANTONIO – Fulvestrant administered at 500 mg in women with locally advanced or metastatic breast cancer results in clinically meaningful improvement in survival without increased toxicity compared with the formerly standard monthly 250-mg dose, according to the final analysis of overall survival in the CONFIRM trial.
CONFIRM (Comparison of Faslodex in Recurrence of Metastatic Breast Cancer) was a phase III, randomized, double-blind clinical trial involving 736 postmenopausal women at 128 centers in 17 countries. All had estrogen receptor–positive locally advanced or metastatic disease. They were randomized to 250 mg of intramuscular fulvestrant (Faslodex) every 28 days, which was then the approved dose, or to 500 mg on days 0, 14, and 28 and every 28 days thereafter.
Dr. Angelo Di Leo
"Based on the results of the present trial, we believe that whenever fulvestrant is considered for the treatment of postmenopausal patients with estrogen receptor-positive advanced breast cancer, the recommended dose is 500 mg," Dr. Angelo Di Leo declared in presenting the CONFIRM update at the annual San Antonio Breast Cancer Symposium.
The final data confirm an earlier interim analysis (J. Clin. Oncol. 2010;28:4594-600), which also showed a survival advantage for the doubled dose. Observers commented that the new analysis provides clinicians with reassurance that the Food and Drug Administration was correct in 2010 when, on the strength of the interim CONFIRM analysis, the agency replaced the 250-mg dose with 500 mg as the approved dose.
The final overall survival analysis was performed when 75% of study participants had died. Fulvestrant at 500 mg was associated with a "clinically meaningful" 4.1-month increase in overall survival: 26.4 months as compared with 22.3 months in the 250-mg group (P = .016). This translated to a 19% reduction in the risk of death, said Dr. Di Leo, head of the department of medical oncology at the Tuscan Tumor Institute at the Hospital of Prato (Italy).
The safety findings were particularly striking. The high and low doses of fulvestrant were associated with similar rates of serious adverse events. There were five serious adverse events leading to death in the 500-mg group and seven in the 250-mg group. Coupled with the survival advantage, the safety data show "without any doubt" that 500 mg monthly is the correct dose, he noted in an interview with this publication.
The CONFIRM trial was sponsored by AstraZeneca. Dr. Di Leo reported that he serves as an adviser to the pharmaceutical company.