title: Fulvestrant for advanced breast cancer: a meta-analysis.
abstract: BACKGROUND
  Fulvestrant is an endocrine agent which degrades the estrogen receptor, thereby downregulating its signaling. Trials of fulvestrant are limited by inconsistent study populations and drug dosing. The optimal use of fulvestrant in advanced breast cancer is therefore unclear.
  
  
  METHODS
  A systematic review of electronic databases was conducted to identify randomized trials of fulvestrant versus other endocrine therapy. The hazard ratios (HR) for time to progression (TTP) and the odds ratios (OR) for serious adverse events (SAEs), discontinuation of treatment due to toxicity and commonly reported toxicities (hot flashes, venous thrombosis, gastrointestinal disturbance, arthralgia, and asthenia) were pooled in a meta-analysis. Meta-regression explored heterogeneity in study population and fulvestrant dosing.
  
  
  RESULTS
  Eight studies were included in the analysis. Overall, there was no difference in TTP between fulvestrant and control groups (HR: 0.94, p=0.18). On meta-regression, fulvestrant showed reduced hazards for TTP compared to aromatase inhibitors (AI) if used in first line, in studies where fewer patients received adjuvant endocrine therapy and at higher doses. Rates of SAEs and treatment discontinuation were similar for fulvestrant and control groups, but fulvestrant monotherapy was associated with significantly less arthralgia (OR: 0.73, p=0.02). The addition of fulvestrant to AI was not associated with improved TTP, but led to increased toxicity.
  
  
  CONCLUSIONS
  In unselected patients, fulvestrant monotherapy is associated with similar efficacy, but reduced arthralgia compared with other endocrine therapy options. Use of high dose fulvestrant monotherapy in first line or in patients with limited prior exposure to adjuvant endocrine therapy may delay progression compared with AI.
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, Canada.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Al-Mubarak
authors.forename: Adrian G
authors.initials: AG
authors.lastname: Sacher
authors.forename: Alberto
authors.initials: A
authors.lastname: Ocana
authors.forename: Francisco
authors.initials: F
authors.lastname: Vera-Badillo
authors.forename: Bostjan
authors.initials: B
authors.lastname: Seruga
authors.forename: Eitan
authors.initials: E
authors.lastname: Amir
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D004958:Estradiol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004965:Estrogen Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D009367:Neoplasm Staging; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D004965:Estrogen Antagonists; D000077267:Fulvestrant; D004958:Estradiol
keywords: Aromatase inhibitors; Breast cancer; Fulvestrant; Tamoxifen