Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial
Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial
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DOI：
10.1016/s1470-2045(07)70385-6
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发表时间：
2008-01-01
期刊：
影响因子：
51.1
通讯作者：
Williams, Norman
中科院分区：
文献类型：
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作者：
Williams, Norman
芳香酶抑制剂辅助治疗5年后，疗效获益或副作用是否持续存在的数据很少。我们的目的是研究长期的结果在Arimidex，他莫昔芬，单独或联合（ATAC）试验，比较阿那曲唑与他莫昔芬后，中位数随访100 months.Methods我们分析了绝经后妇女局部浸润性乳腺癌。在总人群中评估主要终点无病生存期（DFS）和次要终点至复发时间（TTR）、新发对侧乳腺癌（CLBC）发生率、至远处复发时间（TTDR）、总生存期（OS）和复发后死亡（意向治疗; ITT：阿那曲唑，n=3125;他莫昔芬，n=3116;总数6241）和激素受体阳性亚群，目前已知内分泌治疗有效的临床重要亚组（ITT的84%：阿那曲唑，n=2618;他莫昔芬，n=2598;总计5216）。治疗完成后，继续盲法收集骨折和严重不良事件（安全性人群：阿那曲唑，n=3092;他莫昔芬，n=3094;总计6186）。这项研究被注册为国际标准随机对照试验，编号为ISRCTN 18233230。结果在中位随访100个月（范围0.126）时，ITT和β受体阳性人群的DFS、TTR、TTDR和CLBC显著改善。对于受体阳性患者：DFS风险比（HR）0.85（95% CI 0.76-0.94），p=0.003; TTR HR 0.76（0.67.0.87），p=0.0001; TTDR HR 0.84（0.72.0.97），p=0.022;和CLBC HR 0.60（0.42.0.85），p=0.004。至复发时间的绝对差异随时间推移而增加（5年时TTR为2.8% [阿那曲唑9.7% vs他莫昔芬12.5%]，9年时为4.8% [阿那曲唑17.0% vs他莫昔芬21.8%]），治疗完成后，阿那曲唑组的复发率仍显著低于他莫昔芬组（HR 0.75 [0.61.0.941，p=0.01）。复发后死亡人数减少（阿那曲唑245 vs他莫昔芬269）不显著（HR 0.90 [0.75.1.071]，p=0.2），对OS无影响（阿那曲唑472 vs他莫昔芬477）HR 0.97 [0.86.1.11]，p=0.7）。在积极治疗期间，接受阿那曲唑治疗的患者骨折发生率高于接受他莫昔芬治疗的患者（例数[年发生率]：375 [2.93%] vs 234 [1.90%];发生率比[IRR] 1.55 [1.31.1.83]，p
Background Little data exist on whether efficacy benefits or side-effects persist after 5 years of adjuvant treatment with an aromatase inhibitor. We aimed to study long-term outcomes in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial that compares anastrozole with tamoxifen after a median follow-up of 100 months.Methods We analysed postmenopausal women with localised invasive breast cancer. The primary endpoint diseasefree survival (DFS), and the secondary endpoints time to recurrence (TTR), incidence of new contralateral breast cancer (CLBC), time to distant recurrence (TTDR), overall survival (OS), and death after recurrence were assessed in the total population (intention to treat; ITT: anastrozole, n=3125; tamoxifen, n=3116; total 6241) and the hormonereceptor-positive subpopulation, the clinically important subgroup for which endocrine treatment is now known to be effective (84% of ITT: anastrozole, n=2618; tamoxifen, n=2598; total 5216). After treatment completion, fractures and serious adverse events continued to be collected blindly (safety population: anastrozole, n=3092; tamoxifen, n=3094; total 6186). This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN18233230.Findings At a median follow-up of 100 months (range 0.126), DFS, TTR, TTDR, and CLBC were improved significantly in the ITT and hormone-receptor-positive populations. For hormone-receptor-positive patients: DFS hazard ratio (HR) 0.85 (95% CI 0.76-0.94), p=0.003; TTR HR 0.76 (0.67.0.87), p=0.0001; TTDR HR 0.84 (0.72.0.97), p=0.022; and CLBC HR 0.60 (0.42.0.85), p=0.004. Absolute differences in time to recurrence increased over time (TTR 2.8% [anastrozole 9.7% vs tamoxifen 12.5%] at 5 years and 4.8% [anastrozole 17.0% vs tamoxifen 21.8%] at 9 years) and recurrence rates remained significantly lower on anastrozole compared with tamoxifen after treatment completion (HR 0.75 [0.61.0.941, p=0.01). The fewer deaths after recurrence (anastrozole 245 vs tamoxifen 269) was not significant (HR 0.90 [0.75.1.071, p=0.2), and no effect was noted for OS (anastrozole 472 vs tamoxifen 477) HR 0.97 [0.86.1.11], p=0.7). Fracture rates were higher in patients receiving anastrozole than in those receiving tamoxifen during active treatment (number [annual rate]: 375 [2.93%] vs 234 [1.90%]; incidence rate ratio [IRR] 1.55 [1.31.1.83], p