Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial
Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial
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DOI：
10.1016/s0140-6736(07)60200-1
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发表时间：
2007-02-17
期刊：
影响因子：
168.9
通讯作者：
Bliss, J. M.
中科院分区：
文献类型：
--
作者：
Coombes, R. C.;Kilburn, L. S.;Bliss, J. M.
背景：在雌激素受体阳性的早期乳腺癌绝经后妇女中，当芳香化酶抑制剂替代他莫昔芬或在他莫昔芬之后顺序给予芳香化酶抑制剂时，已经注意到早期无病生存率的改善。然而，芳香酶抑制剂治疗后的长期效果，以及这些早期改善是否会带来真正的生存改善，目前还没有多少信息。方法4724例绝经后乳腺癌患者，在接受他莫昔芬治疗2-3年后，没有任何疾病发生，他们被随机分为两组，分别改用依西美坦(n=2352)或继续他莫昔芬(n=2372)进行5年内分泌治疗。主要终点是无病存活率；总体存活率是次要终点。疗效分析采用意向处理。本研究注册为国际标准随机对照试验，编号为ISRCTN11883920。结果经过55.7个月(范围0-89.7)的中位随访期，报告了809个有助于无病生存分析的事件(354个西西美坦，455个三苯氧胺)；未调整的危险比为0.76(95%可信区间0.66~0.88，p=0.0001)，治疗结束时的绝对收益为3.3%(95%可信区间1.6~4.9)。在排除122例雌激素受体阴性疾病患者后，未调整风险比为0.85(95%CI 0.71-1.02，p=0.08)，0.83(0.69-1.00，p=0.05)。结论我们的结果表明，在服用他莫昔芬2-3年后改用依西美坦的患者，早期无病生存期的改善持续存在，并转化为总体生存期的温和改善。
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.