BIG 1-98 试验更新：我们现在处于什么位置？

Update of the BIG 1-98 Trial: where do we stand?

机构信息

Breast Center, Cantonal Hospital, St. Gallen, Switzerland.

出版信息

Breast. 2009 Oct;18 Suppl 3:S78-82. doi: 10.1016/S0960-9776(09)70278-4.

DOI:10.1016/S0960-9776(09)70278-4

PMID:19914548

Abstract

BACKGROUND AND METHODS

There is accumulating data on the clinical benefit of aromatase inhibitors in the adjuvant treatment of early-stage breast cancer in postmenopausal women. The Breast International Group (BIG) 1-98 study is a randomized, phase 3, double-blind trial comparing four adjuvant endocrine treatments of 5 years duration in postmenopausal women with hormone-receptor-positive breast cancer: letrozole or tamoxifen monotherapy, sequential treatment with tamoxifen followed by letrozole, or vice versa. This article summarizes data presented at the 2009 St. Gallen early breast cancer conference: an update on the monotherapy arms of the BIG 1-98 study, and results from the sequential treatment arms. Implications for daily practice from BIG 1-98 and from other adjuvant trials will be discussed.

RESULTS

Despite cross-over from tamoxifen to letrozole by 25% of the patients after unblinding of the tamoxifen monotherapy arm, the improvement of disease-free survival (HR 0.88, 0.78-0.99, p = 0.03) and time to distant recurrence (HR 0.85, 0.72-1.00, p = 0.05) for letrozole monotherapy as compared to tamoxifen monotherapy remained significant in the intention-to-treat (ITT) analysis. A trend for an overall survival advantage for letrozole was seen in the ITT analysis (HR 0.87, 0.75-1.02, p = 0.08). No statistically significant differences were found for the sequential treatment arms versus letrozole monotherapy, with respect to disease-free survival, time to distant recurrence or overall survival. Cumulative incidence analysis of breast cancer recurrence favors the initiation of adjuvant endocrine treatment with letrozole instead of tamoxifen, especially in patients at higher risk for early recurrence. Similarly, data suggest that patients commenced on letrozole can be switched to tamoxifen after 2 years, if required.

CONCLUSIONS

The BIG 1-98 study update with median follow up of 76 months confirms a significant reduction in the risk of breast cancer recurrence and a trend towards improved overall survival with letrozole as compared to tamoxifen, and no unexpected safety concerns with letrozole. Adjuvant endocrine treatment should preferentially be initiated with letrozole. For patients unable to continue letrozole, switching to tamoxifen appears to be an acceptable alternative.

摘要

背景与方法

越来越多的数据表明芳香化酶抑制剂在绝经后女性早期乳腺癌的辅助治疗中具有临床获益。BIG 1-98 研究是一项随机、III 期、双盲试验，比较了 5 年激素受体阳性乳腺癌绝经后妇女的四种辅助内分泌治疗方法：来曲唑或他莫昔芬单药治疗、序贯治疗（先用他莫昔芬，后用来曲唑；或反之）。本文总结了 2009 年圣加仑早期乳腺癌会议上报告的 BIG 1-98 研究的单药治疗臂数据，以及序贯治疗臂的结果。将讨论 BIG 1-98 研究和其他辅助治疗试验对日常实践的影响。

结果

尽管在他莫昔芬单药治疗臂揭盲后，有 25%的患者交叉使用来曲唑，但来曲唑单药治疗与他莫昔芬单药治疗相比，无病生存率（HR 0.88，0.78-0.99，p = 0.03）和远处复发时间（HR 0.85，0.72-1.00，p = 0.05）的改善仍具有统计学意义（意向治疗分析）。意向治疗分析中，来曲唑治疗的总生存优势呈趋势（HR 0.87，0.75-1.02，p = 0.08）。与来曲唑单药治疗相比，序贯治疗臂在无病生存率、远处复发时间或总生存率方面均无统计学差异。乳腺癌复发的累积发生率分析有利于起始辅助内分泌治疗使用来曲唑而不是他莫昔芬，尤其是在早期复发风险较高的患者中。同样，数据表明，如果需要，起始治疗使用来曲唑的患者可在 2 年后转换为他莫昔芬。