Treatment Adherence and Its Impact on Disease-Free Survival in the Breast International Group 1-98 Trial of Tamoxifen and Letrozole, Alone and in Sequence
Treatment Adherence and Its Impact on Disease-Free Survival in the Breast International Group 1-98 Trial of Tamoxifen and Letrozole, Alone and in Sequence
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DOI：
10.1200/jco.2015.63.8619
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发表时间：
2016-07-20
影响因子：
45.3
通讯作者：
Thurlimann, Beat
中科院分区：
文献类型：
--
作者：
Chirgwin, Jacquie H.;Giobbie-Hurder, Anita;Thurlimann, Beat
目的探讨乳腺国际组织(BIG)1-98临床试验中对内分泌治疗的依从性及其与无病生存(DFS)的关系。方法BIG 1-98临床试验为双盲试验，将6193例激素受体阳性的早期乳腺癌患者随机分为3组，每组6 193例，分别给予他莫昔芬()、来曲唑(LET)或顺序药(LET-、-LET)治疗。这项分析包括6144名接受至少一剂研究治疗的女性。使用条件里程碑分析和边际结构COX比例风险模型评估DFS与治疗依从性(持续性[持续时间]和服药依从性)之间的关系。结果低依从性(早期停止来曲唑和依从性评分90%)与DFS降低相关(多变量模型风险比1.45；95%可信区间1.09至1.93；P=0.01；多变量模型风险比1.61；95%可信区间1.08至2.38；P=0.02)。序贯治疗与较高的非持续性相关(-莱特，20.8%；让-，20.3%；，16.9%；让-17.6%)。不良事件是大多数试验治疗提前中止的原因(82.7%)。除序贯治疗分配外，依从性降低还与年龄大、吸烟、结节阴性或既往血栓栓子事件有关。毒性管理，以及对于顺序治疗，患者和医生的意识，可能会提高依从性。(C)2016年度美国临床肿瘤学会
PurposeTo investigate adherence to endocrine treatment and its relationship with disease-free survival (DFS) in the Breast International Group (BIG) 1-98 clinical trial.MethodsThe BIG 1-98 trial is a double-blind trial that randomly assigned 6,193 postmenopausal women with hormone receptor-positive early breast cancer in the four-arm option to 5 years of tamoxifen (Tam), letrozole (Let), or the agents in sequence (Let-Tam, Tam-Let). This analysis included 6,144 women who received at least one dose of study treatment. Conditional landmark analyses and marginal structural Cox proportional hazards models were used to evaluate the relationship between DFS and treatment adherence (persistence [duration] and compliance with dosage). Competing risks regression was used to assess demographic, disease, and treatment characteristics of the women who stopped treatment early because of adverse events.ResultsBoth aspects of low adherence (early cessation of letrozole and a compliance score of < 90%) were associated with reduced DFS (multivariable model hazard ratio, 1.45; 95% CI, 1.09 to 1.93; P = .01; and multivariable model hazard ratio, 1.61; 95% CI, 1.08 to 2.38; P = .02, respectively). Sequential treatments were associated with higher rates of nonpersistence (Tam-Let, 20.8%; Let-Tam, 20.3%; Tam 16.9%; Let 17.6%). Adverse events were the reason for most trial treatment early discontinuations (82.7%). Apart from sequential treatment assignment, reduced adherence was associated with older age, smoking, node negativity, or prior thromboembolic event.ConclusionBoth persistence and compliance are associated with DFS. Toxicity management and, for sequential treatments, patient and physician awareness, may improve adherence. (C) 2016 by American Society of Clinical Oncology