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

作者：Jacquie H. Chirgwin, Anita Giobbie‐Hurder, Alan Stuart Coates, Karen N. Price, Bent Ejlertsen, Marc Debled, Richard D. Gelber, Aron Goldhirsch, Ian Smith, Manuela Rabaglio, John Forbes, Patrick Neven, István Láng, Marco Angelo Colleoni, Beat J. K. Thurlimann · 发表于：Journal of Clinical Oncology · 年份：2016 · DOI：10.1200/jco.2015.63.8619 · 被引用次数：254 · 研究领域：Medication Adherence and Compliance、BRCA gene mutations in cancer、Advanced Breast Cancer Therapies

PURPOSE: To investigate adherence to endocrine treatment and its relationship with disease-free survival (DFS) in the Breast International Group (BIG) 1-98 clinical trial. METHODS: The 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. RESULTS: Both 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 ...