氟维司群治疗晚期乳腺癌：一项Meta分析

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.

Conclusion
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.

结论：在未经选择的患者中，与其他内分泌治疗手段相比，氟维司群单药治疗的疗效相似，但关节痛的发生更少。在一线或之前接受较少辅助内分泌治疗的患者中，与芳香化酶抑制剂相比，大剂量氟维司群单药治疗可延缓肿瘤的进展。