Fulvestrant for advanced breast cancer: A meta-analysis.

Abstract

e11613 Background: Fulvestrant is an endocrine agent which degrades the estrogen receptor, thereby downregulating its signaling. While fulvestrant has been consistently tested in postmenopausal women with inoperable locally advanced or metastatic breast cancer, there has been substantial heterogeneity in 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, 95% CI 0.85-1.03, p=0.18). On meta-regression, fulvestrant showed reduced hazards for TTP compared to aromatase inhibitors (AI) if used in first line (p for trend <0.001), in studies where fewer patients received adjuvant endocrine therapy (p for trend <0.001) and at higher doses (p for trend <0.001). Rates of SAEs and treatment discontinuation were similar for fulvestrant and control groups, but fulvestrant monotherapy was associated with significantly less arthralgia (OR:0.73,95% CI 0.57-0.95, p=0.02). The addition of fulvestrant to AI compared with AI alone was not associated with improved TTP (HR:0.88, 0.72-1.09,P=0.25), but led to increased hot flashes (OR: 1.68,95% CI 1.30-2.16, P<0.001) and gastrointestinal disturbances (OR:1.28, , 95% CI 1.01-1.63, p=0.04). Conclusions: In unselected patients, fulvestrant monotherapy is associated with similar efficacy, but reduced arthralgia. 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. Fulvestrant combined with AI was not associated with improved efficacy but led to increased toxicity.