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Metastatic breast cancer: sequencing hormonal therapy and positioning of fulvestrant
1Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, University Hospitals, Katholieke Universiteit Leuven, Belgium. Ignace.Vergote@uz.kuleuven.ac.be
Abstract:
Fulvestrant, a novel estrogen receptor (ER) antagonist with no agonist effects, binds, blocks, and degrades the ER, thereby downregulating cellular ER levels, which in turn leads to reduced expression of the progesterone receptor. Due to this specific working mechanism, fulvestrant is an important addition to the armamentarium of endocrine agents in advanced breast cancer (ABC). Fulvestrant has been shown to be equally effective as the third-generation aromatase inhibitor (AI) anastrozole in postmenopausal patients with hormone-sensitive ABC progressing prior to tamoxifen. In another randomized phase III trial, it was shown that fulvestrant had similar efficacy to tamoxifen in the first-line treatment of postmenopausal women with hormone receptor-positive ABC. When comparing the side effects of fulvestrant with tamoxifen and anastrozole, it was shown that fulvestrant is well tolerated compared with these agents and is associated with a lower incidence of joint disorders. Clinical benefit on fulvestrant treatment after AI therapy has been reported in a substantial number of patients (28-46%). On the other hand, it was also shown that sensitivity to further endocrine therapy is retained following progression on first-line or second-line fulvestrant (57% and 46% clinical benefit, respectively). In conclusion, fulvestrant provides us with an additional endocrine treatment option making it possible to prolong the time that patients with ABC can be treated with endocrine therapy.
Insights
Fulvestrant, an estrogen receptor (ER) antagonist, offers an effective endocrine therapy option for advanced breast cancer (ABC). It shows comparable efficacy to anastrozole and tamoxifen with fewer joint-related side effects.
Area of Science:
- Endocrinology
- Oncology
- Pharmacology
Background:
- Fulvestrant is a novel estrogen receptor (ER) antagonist.
- It functions by binding, blocking, and degrading ER, thus downregulating ER levels.
- This mechanism reduces progesterone receptor expression, making it valuable for advanced breast cancer (ABC).
Purpose of the Study:
- To evaluate fulvestrant as an endocrine therapy for advanced breast cancer (ABC).
- To compare fulvestrant's efficacy and side effect profile against anastrozole and tamoxifen.
- To assess the clinical benefit of fulvestrant after aromatase inhibitor (AI) therapy and its impact on subsequent endocrine therapies.
Main Methods:
- Randomized phase III trials were conducted comparing fulvestrant to anastrozole and tamoxifen.
- Efficacy and side effect profiles were assessed in postmenopausal women with hormone-sensitive or hormone receptor-positive ABC.
- Clinical benefit was evaluated in patients treated with fulvestrant after AI therapy and after progression on fulvestrant.
Main Results:
- Fulvestrant demonstrated equal efficacy to anastrozole in postmenopausal patients with hormone-sensitive ABC progressing on tamoxifen.
- Fulvestrant showed similar efficacy to tamoxifen in the first-line treatment of postmenopausal women with hormone receptor-positive ABC.
- Fulvestrant was well tolerated, with a lower incidence of joint disorders compared to tamoxifen and anastrozole. Clinical benefit was observed in 28-46% of patients after AI therapy, and sensitivity to further endocrine therapy was retained after fulvestrant progression.
Conclusions:
- Fulvestrant is an effective endocrine agent for advanced breast cancer (ABC).
- It offers a favorable side effect profile, particularly regarding joint disorders.
- Fulvestrant provides an additional treatment option, potentially prolonging endocrine therapy duration for ABC patients.
