他莫昔芬治疗2 - 3年后依西美坦与他莫昔芬的生存情况及安全性比较（国际依西美坦研究组）：一项随机对照试验

Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial.

作者信息

Coombes R C, Kilburn L S, Snowdon C F, Paridaens R, Coleman R E, Jones S E, Jassem J, Van de Velde C J H, Delozier T, Alvarez I, Del Mastro L, Ortmann O, Diedrich K, Coates A S, Bajetta E, Holmberg S B, Dodwell D, Mickiewicz E, Andersen J, Lønning P E, Cocconi G, Forbes J, Castiglione M, Stuart N, Stewart A, Fallowfield L J, Bertelli G, Hall E, Bogle R G, Carpentieri M, Colajori E, Subar M, Ireland E, Bliss J M

机构信息

Cancer Research UK Department of Cancer Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Imperial College London, Faculty of Medicine, Hammersmith Hospitals Trust, London W12 0NN, UK.

出版信息

Lancet. 2007 Feb 17;369(9561):559-70. doi: 10.1016/S0140-6736(07)60200-1.

DOI:10.1016/S0140-6736(07)60200-1

PMID:17307102

Abstract

BACKGROUND

Early improvements in disease-free survival have been noted when an aromatase inhibitor is given either instead of or sequentially after tamoxifen in postmenopausal women with oestrogen-receptor-positive early breast cancer. However, little information exists on the long-term effects of aromatase inhibitors after treatment, and whether these early improvements lead to real gains in survival.

METHODS

4724 postmenopausal patients with unilateral invasive, oestrogen-receptor-positive or oestrogen-receptor-unknown breast cancer who were disease-free on 2-3 years of tamoxifen, were randomly assigned to switch to exemestane (n=2352) or to continue tamoxifen (n=2372) for the remainder of a 5-year endocrine treatment period. The primary endpoint was disease-free survival; overall survival was a secondary endpoint. Efficacy analyses were intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN11883920.

RESULTS

After a median follow-up of 55.7 months (range 0-89.7), 809 events contributing to the analysis of disease-free survival had been reported (354 exemestane, 455 tamoxifen); unadjusted hazard ratio 0.76 (95% CI 0.66-0.88, p=0.0001) in favour of exemestane, absolute benefit 3.3% (95% CI 1.6-4.9) by end of treatment (ie, 2.5 years after randomisation). 222 deaths occurred in the exemestane group compared with 261 deaths in the tamoxifen group; unadjusted hazard ratio 0.85 (95% CI 0.71-1.02, p=0.08), 0.83 (0.69-1.00, p=0.05) when 122 patients with oestrogen-receptor-negative disease were excluded.

CONCLUSIONS

Our results suggest that early improvements in disease-free survival noted in patients who switch to exemestane after 2-3 years on tamoxifen persist after treatment, and translate into a modest improvement in overall survival.

摘要

背景

对于雌激素受体阳性的早期乳腺癌绝经后女性，在他莫昔芬治疗后改用芳香化酶抑制剂或在他莫昔芬之后序贯使用芳香化酶抑制剂，已观察到无病生存期的早期改善。然而，关于芳香化酶抑制剂治疗后的长期影响，以及这些早期改善是否能带来真正的生存获益，相关信息较少。

方法

4724例绝经后单侧浸润性乳腺癌患者，雌激素受体阳性或雌激素受体情况未知，在接受2 - 3年他莫昔芬治疗后病情无进展，被随机分配改为依西美坦治疗（n = 2352）或继续他莫昔芬治疗（n = 2372），进行为期5年的内分泌治疗。主要终点为无病生存期；总生存期为次要终点。疗效分析采用意向性治疗。本研究注册为国际标准随机对照试验，编号ISRCTN11883920。

结果

中位随访55.7个月（范围0 - 89.7个月）后，报告了809例有助于无病生存期分析的事件（依西美坦组354例，他莫昔芬组455例）；未调整的风险比为0.76（95%可信区间0.66 - 0.88，p = 0.0001），支持依西美坦，治疗结束时（即随机分组后2.5年）绝对获益为3.3%（95%可信区间1.6 - 4.9）。依西美坦组发生222例死亡，他莫昔芬组发生261例死亡；未调整的风险比为0.85（95%可信区间0.71 - 1.02，p = 0.08），排除122例雌激素受体阴性疾病患者后为0.83（0.69 - 1.00，p = 0.05）。