Fulvestrant in hormonal treatment of breast cancer

Abstract

Fulvestrant is a selective oestrogen receptor (ER) down-regulator (SERD), which lacks partial agonistic properties characteristic for selective oestrogen receptor modulators (SERM). The drug is indicated for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antioestrogen therapy. The initial recommendation of a 250-mg dose was based on the results of clinical trials, which revealed that fulvestrant was non-inferior to anastrozole in this indication. However, the higher the dose of fulvestrant, the more effective it is. The CONFIRM trial compared a 500-mg dose with the approved dose of fulvestrant of 250 mg per month for treatment of postmenopausal women with oestrogen receptor-positive advanced breast cancer, who progressed after prior endocrine therapy. It showed that the higher dose was associated with a statistically significant increase in progression-free survival without increased toxicity, and it became the basis of approval of a fulvestrant dose of 500 mg in 2010. The drug should be administered intramuscularly on days 0, 14 and 28 and once monthly thereafter. The phase III FALCON trial, to which postmenopausal breast cancer patients who had not received previous endocrine therapy were eligible, revealed that a 500-mg fulvestrant dose reduced the risk of progression by 20% compared with anastrozole in first-line treatment. Fulvestrant is also beneficial in third and further lines of hormonal treatment of breast cancer and remains efficacious in young patients treated with LHRH analogue. There have also been numerous trials investigating the efficacy of fulvestrant combined with molecular targeted therapy in patients with hormone-resistant metastatic breast cancers. This review summarises the mechanism of action of fulvestrant and the results of the most important clinical trials dedicated to this drug.