【原】氟维司群治疗晚期乳腺癌：两支与一支、一线或二线

　　双盲三期研究CONFIRM（NCT00099437）已经确认氟维司群500mg与氟维司群250mg相比，可使绝经后激素受体阳性局部晚期或转移性乳腺癌女性的中位总生存延长4.1个月，死亡风险减少19%（P=0.02）。

　　2018年1月8日，欧洲乳腺癌专科学会《乳腺》在线发表意大利普拉托医院、比利时列日大学、智利国家癌症研究所、比利时安特卫普大学、美国堪萨斯大学癌症中心、英国阿斯利康、西班牙马德里大学的CONFIRM研究结果分析报告，调查了氟维司群对于晚期乳腺癌一线或二线治疗的有效性和安全性。

　　该事后分析使用未校正对数秩检验对氟维司群500mg与氟维司群250mg一线治疗（早期乳腺癌术后辅助内分泌治疗≤12个月复发，387例）和二线治疗（局部晚期或转移性乳腺癌的内分泌治疗，343例）的无进展生存和总生存进行评估。

　　结果，氟维司群500mg与250mg相比：

• 一线治疗的中位无进展生存延长1.4个月（5.6比4.2，P=0.047）复发风险减少20%（风险比：0.80，95%：0.64～1.00）

• 二线治疗的中位无进展生存延长1.6个月（7.9比6.3，P=0.068）复发风险减少20%（风险比：0.80，95%：0.64～1.02）

• 一线治疗的中位总生存延长1.1个月（23.2比22.1，P=0.251）死亡风险减少13%（风险比：0.87，95%：0.70～1.10）

• 二线治疗的中位总生存延长6.4个月（29.2比22.8，P=0.020）死亡风险减少25%（风险比：0.75，95%：0.58～0.96）

• 注：中位总生存数据截至四分之三患者死亡时。

　　两组剂量之间和两线治疗之间的安全性特征大致相似，并且与患者总体人群一致。

　　因此，对于CONFIRM研究的局部晚期或转移性乳腺癌患者，氟维司群500mg与氟维司群250mg相比，一线与二线治疗的无进展生存和总生存均有优势，尤其一线治疗的无进展生存、二线治疗的总生存显著延长。

Breast. 2018 Jan 8;38:144-149. [Epub ahead of print]

First-line vs second-line fulvestrant for hormone receptor-positive advanced breast cancer: A post-hoc analysis of the CONFIRM study.

Angelo Di Leo, Guy Jerusalem, Roberto Torres, Didier Verhoeven, Kelly Pendergrass, Luca Malorni, Jasmine Lichfield, Miguel Martin.

Hospital of Prato, Istituto Toscano Tumori, Prato, Italy; CHU Sart Tilman Liège and Liège University, Liège, Belgium; Instituto Nacional del Cáncer, Independencia, Santiago, Región Metropolitana, Chile; University of Antwerp, Antwerpen, Belgium; University of Kansas Cancer Center, Kansas City, MO, USA; AstraZeneca, Melbourn, Royston, Herts, UK; Instituto de Investigación Sanitaria Gregorio Maranón, Universidad Complutense, Madrid, Spain.

HIGHLIGHTS

• The phase III CONFIRM study investigated fulvestrant 500 mg vs 250 mg for HR + LA/MBC.

• We performed a post-hoc analysis according to line of therapy for advanced disease.

• Effect of fulvestrant 500 mg vs 250 mg was consistent in first- and second-line.

OBJECTIVES: The double-blind, phase III CONFIRM study (NCT00099437) evaluated fulvestrant 500 mg vs fulvestrant 250 mg in postmenopausal women with hormone receptor-positive locally advanced/metastatic breast cancer (LA/MBC). This post-hoc analysis investigated the efficacy and safety of fulvestrant given either first-line or second-line for advanced disease.

MATERIALS & METHODS: Progression-free survival (PFS) and overall survival (OS) with fulvestrant 500 mg vs fulvestrant 250 mg was evaluated using unadjusted log-rank tests in patients treated in the first- (progression during or within 12 months after completing adjuvant endocrine therapy; n = 387) and second-line (following endocrine therapy for LA/MBC; n = 343) settings.

RESULTS: First-line fulvestrant 500 mg significantly prolonged PFS vs fulvestrant 250 mg (median PFS 5.6 vs 4.2 months; hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.64-1.00; p = .047). Median PFS was numerically greater with second-line fulvestrant 500 mg vs fulvestrant 250 mg (7.9 vs 6.3 months; HR 0.80; 95% CI 0.64-1.02; p = .068). At data cut-off (75.5% maturity), median OS with first-line fulvestrant 500 mg was 23.2 vs 22.1 months with fulvestrant 250 mg (HR 0.87; 95% CI 0.70-1.10; p = .251), and 29.2 vs 22.8 months, respectively, in the second-line (HR 0.75; 95% CI 0.58-0.96; p = .020). The safety profile was broadly comparable between dose groups and across treatment lines, and consistent with the overall patient population.

CONCLUSION: The superiority of fulvestrant 500 mg over fulvestrant 250 mg in patients with LA/MBC in CONFIRM was consistent in both the first- and second-line settings for PFS, and numerically greater in both settings for OS.

KEYWORDS: Advanced breast cancer; First-line; Fulvestrant; Second-line; Overall survival

DOI: 10.1016/j.breast.2017.12.016