Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial.
Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial.
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DOI：
10.1016/s0140-6736(15)01129-0
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发表时间：
2016-02-27
期刊：
影响因子：
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通讯作者：
IBIS-II investigators
中科院分区：
文献类型：
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作者：
Forbes JF;Sestak I;Howell A;Bonanni B;Bundred N;Levy C;von Minckwitz G;Eiermann W;Neven P;Stierer M;Holcombe C;Coleman RE;Jones L;Ellis I;Cuzick J;IBIS-II investigators
第三代芳香化酶抑制剂比他莫昔芬更有效地预防绝经后妇女乳腺癌受体阳性浸润性乳腺癌的复发。然而，目前尚不清楚阿那曲唑是否比他莫昔芬对乳腺癌受体阳性导管原位癌（DCIS）的女性更有效。在此，我们比较了阿那曲唑与他莫昔芬治疗绝经后乳腺癌受体阳性DCIS妇女的疗效。在一项双盲、多中心、随机、安慰剂对照试验中，我们招募了被诊断为局部切除的乳腺癌受体阳性DCIS的女性。符合条件的妇女通过中心计算机分配以1：1的比例随机分配，每天口服1 mg阿那曲唑或20 mg他莫昔芬，持续5年。随机化按主要中心或中心分层，并在区组（6、8或10）中进行。所有试验工作人员、受试者和临床医生均对治疗分配设盲，只有试验统计学家可以访问治疗分配。主要终点是所有复发，包括复发性DCIS和新的对侧肿瘤。所有分析均在改良的意向治疗基础上进行（在所有接受随机化且未撤销同意纳入其数据的女性中进行），并使用比例风险模型计算风险比和相应的置信区间。本试验在ISRCTN登记处注册，编号ISRCTN 37546358。在2003年3月3日至2012年2月8日期间，我们从14个国家的236个中心招募了2980名绝经后妇女，并将她们随机分配接受阿那曲唑（分析了1449名）或他莫昔芬（分析了1489名）。中位随访时间为7.2年（IQR 5.6 - 8.9），记录了144例乳腺癌复发。我们注意到总复发率无统计学显著差异（阿那曲唑组67例复发，他莫昔芬组77例复发; HR 0.89 [95%CI 0.64 - 1.23]）。确定了阿那曲唑的非劣效性（95%CI上限<1.25），但其相对于他莫昔芬的优效性未确定（p= 0.49）。共记录了69例死亡（阿那曲唑组33例，他莫昔芬组36例; HR 0.93 [95% CI 0.58 - 1.50]，p= 0.78），两组中没有特定原因比另一组更常见。阿那曲唑组（1323例女性，91%）和他莫昔芬组（1379例女性，93%）报告任何不良事件的女性人数相似;两种药物的副作用特征不同，阿那曲唑组骨折、肌肉骨骼事件、高胆固醇血症和中风更多，而他莫昔芬组肌肉痉挛、妇科癌症和症状、血管炎症状和深静脉血栓形成更多。两种治疗之间未观察到明显的疗效差异。阿那曲唑为绝经后乳腺癌受体阳性的DCIS女性提供了另一种治疗选择，这可能更适合于一些有他莫昔芬禁忌症的女性。需要更长时间的随访以充分评价治疗差异。英国癌症研究中心、澳大利亚国家健康和医学研究理事会、乳腺癌研究基金、阿斯利康、赛诺菲安万特。
Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS. In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor-positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358. Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7·2 years (IQR 5·6–8·9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0·89 [95% CI 0·64–1·23]). The non-inferiority of anastrozole was established (upper 95% CI <1·25), but its superiority to tamoxifen was not (p=0·49). A total of 69 deaths were recorded (33 for anastrozole vs 36 for tamoxifen; HR 0·93 [95% CI 0·58–1·50], p=0·78), and no specific cause was more common in one group than the other. The number of women reporting any adverse event was similar between anastrozole (1323 women, 91%) and tamoxifen (1379 women, 93%); the side-effect profiles of the two drugs differed, with more fractures, musculoskeletal events, hypercholesterolaemia, and strokes with anastrozole and more muscle spasm, gynaecological cancers and symptoms, vasomotor symptoms, and deep vein thromboses with tamoxifen. No clear efficacy differences were seen between the two treatments. Anastrozole offers another treatment option for postmenopausal women with hormone-receptor-positive DCIS, which may be be more appropriate for some women with contraindications for tamoxifen. Longer follow-up will be necessary to fully evaluate treatment differences. Cancer Research UK, National Health and Medical Research Council Australia, Breast Cancer Research Fund, AstraZeneca, Sanofi Aventis.