Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer:: Update of study BIG 1-98
Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer:: Update of study BIG 1-98
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DOI：
10.1200/jco.2006.08.8617
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发表时间：
2007-02-10
影响因子：
45.3
通讯作者：
Goldhirsch, Aron
中科院分区：
文献类型：
--
作者：
Coates, Alan S.;Keshaviah, Aparna;Goldhirsch, Aron
研究目的：国际乳腺组（BIG）1-98四臂研究的既往分析比较了来曲唑或他莫昔芬的初始治疗，包括随机分配到序贯治疗组的患者，其信息在治疗改变时被删失。由于这种表现可能不适当地反映了早期事件，本分析仅限于随机分配到连续治疗组的患者，并包括方案定义的更新结果。028例受体阳性的绝经后早期乳腺癌妇女随机分组，BIG 1-98试验中的10名妇女（双盲）被分配接受5年来曲唑或他莫昔芬的连续辅助治疗;其余妇女被分配接受顺序药物治疗。无病生存率（DFS）是主要的endpoint.ResultsAt中位随访时间为51个月，我们观察到352 DFS事件2,463名妇女接受来曲唑和418事件2,459名妇女接受他莫昔芬。这反映了事件风险降低18%（风险比，0.82; 95%CI，0.71 - 0.95; P = 0.007）。没有预定义的子集显示出差异性益处。不良事件与既往报告相似。服用他莫昔芬的患者发生血栓栓塞事件、子宫内膜病变、潮热、盗汗和阴道出血的次数更多。来曲唑的患者经历了更多的骨折，关节痛，低级别高胆固醇血症，缺血和心脏failure.ConclusionThe目前更新的分析，这是有限的单药治疗组的患者在BIG 1-98，产生类似的结果，从以前的主要分析，但更直接可比的结果从其他试验的连续治疗使用单一的内分泌药物。
PurposePrevious analyses of the Breast International Group ( BIG) 1-98 four-arm study compared initial therapy with letrozole or tamoxifen including patients randomly assigned to sequential treatment whose information was censored at the time of therapy change. Because this presentation may unduly reflect early events, the present analysis is limited to patients randomly assigned to the continuous therapy arms and includes protocol-defined updated results.Patients and MethodsFour thousand nine hundred twenty-two of the 8,028 postmenopausal women with receptor-positive early breast cancer randomly assigned (double-blind) to the BIG 1-98 trial were assigned to 5 years of continuous adjuvant therapy with either letrozole or tamoxifen; the remainder of women were assigned to receive the agents in sequence. Disease-free survival (DFS) was the primary end point.ResultsAt a median follow-up time of 51 months, we observed 352 DFS events among 2,463 women receiving letrozole and 418 events among 2,459 women receiving tamoxifen. This reflected an 18% reduction in the risk of an event ( hazard ratio, 0.82; 95% CI, 0.71 to 0.95; P =.007). No predefined subsets showed differential benefit. Adverse events were similar to previous reports. Patients on tamoxifen experienced more thromboembolic events, endometrial pathology, hot flashes, night sweats, and vaginal bleeding. Patients on letrozole experienced more bone fractures, arthralgia, low-grade hypercholesterolemia, and cardiovascular events other than ischemia and cardiac failure.ConclusionThe present updated analysis, which was limited to patients on monotherapy arms in BIG 1-98, yields results similar to those from the previous primary analysis but more directly comparable with results from other trials of continuous therapy using a single endocrine agent.