Supplementary Material for: Patient Preferences for HR+/HER2‒ Early Breast Cancer Adjuvant Treatment: A Multicountry Discrete Choice Experiment

Introduction: More adjuvant treatment options are becoming available for hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) early breast cancer (EBC) based on results of clinical trials. This study quantified the importance of different attributes of EBC adjuvant therapies to patients and the benefit-risk tradeoffs patients were willing to make.
Methods: Women with HR+/HER2– EBC completed an online discrete choice experiment (DCE) survey; the design was informed by clinical data, qualitative interviews (n=40), and pre-testing interviews (n=40). Participants (pts) made 10 choices between pairs of hypothetical treatments described by varying levels of 6 attributes. DCE data were analyzed using a correlated mixed logit model. Relative attribute importance scores captured the impact of each attribute across clinically relevant ranges. Benefit-risk tradeoffs were captured as the minimum improvements in 5-y invasive disease–free survival (iDFS) that pts would require to tolerate increases in therapy-associated adverse event (AE) risks.
Results: A total of 866 patients from the US, France, Spain, Canada, the UK, Germany, South Korea, and Australia completed the DCE (mean age: 57.7 y; 76% postmenopausal; 29% stage I disease, 55% stage II, 16% stage III). Improved 5-y iDFS (75.4-82.7% range; associated with combination regimens [CRs] vs endocrine therapy [ET] alone) contributed the most to treatment preferences (clinically relevant relative attribute importance: 38.4%), followed by reduced risks of venous thromboembolic events (VTEs) (20.4%), neutropenia (20.3%), and diarrhea (15.0%). Treatment type + duration (3.7%) and fatigue (2.3%) were less important. Pts required the largest improvement in 5-y iDFS (3.9%) to tolerate increased risks of VTE (0.7% to 2.5%) or neutropenia (5.6% to 46%); willingness to accept tradeoffs depended on the AE. Preference heterogeneity was observed across subgroups, but 5-y iDFS improvement was consistently the most impactful on treatment choice in all subgroups.
Conclusion: A multicountry sample of patients most valued adjuvant therapies with higher 5-y iDFS and may therefore prefer CRs over ET alone. The value of CRs depends on their specific safety profiles, and shared decision-making should consider this to select treatment options that align with individual preferences.

研究背景：基于多项临床试验结果，激素受体阳性/人表皮生长因子受体2阴性（HR+/HER2–）早期乳腺癌（Early Breast Cancer, EBC）的辅助治疗可选方案正日益丰富。本研究量化了EBC辅助治疗的不同属性对患者的重要性，以及患者愿意做出的获益-风险权衡。
研究方法：HR+/HER2–早期乳腺癌女性患者完成了线上离散选择实验（Discrete Choice Experiment, DCE）问卷；问卷设计参考了临床数据、定性访谈（n=40）及预测试访谈（n=40）。受试者（pts，即患者）需在10组由6种属性的不同水平组合而成的假想治疗方案中做出选择。采用相关混合Logit模型分析DCE数据，相对属性重要性评分用于衡量各属性在临床相关范围内的影响。获益-风险权衡通过患者为耐受治疗相关不良事件（Adverse Event, AE）风险增加所要求的5年无浸润性疾病生存期（invasive disease-free survival, iDFS）最小提升幅度来体现。
研究结果：来自美国、法国、西班牙、加拿大、英国、德国、韩国及澳大利亚的共866例患者完成了本次离散选择实验（平均年龄57.7岁；76%为绝经后；29%为I期疾病，55%为II期，16%为III期）。5年iDFS的改善（范围75.4%~82.7%，对应联合治疗方案（Combination Regimens, CRs）对比单纯内分泌治疗（Endocrine Therapy, ET））对治疗偏好的影响最大（临床相关相对属性重要性为38.4%），其次为静脉血栓栓塞事件（Venous Thromboembolic Events, VTE）风险降低（20.4%）、中性粒细胞减少（20.3%）及腹泻（15.0%）。治疗类型+疗程（3.7%）与疲劳（2.3%）的重要性相对较低。患者为耐受VTE风险升高（0.7%~2.5%）或中性粒细胞减少风险升高（5.6%~46%），所需的5年iDFS最大提升幅度为3.9%；患者的权衡意愿因不良事件类型而异。各亚组间均存在偏好异质性，但5年iDFS改善始终对所有亚组的治疗选择影响最大。
研究结论：多国家队列的患者最看重5年iDFS更高的辅助治疗方案，因此相较单纯内分泌治疗，患者或更偏好联合治疗方案。联合治疗方案的价值取决于其特定的安全性特征，共享决策应考虑这一点，以选择符合患者个体偏好的治疗方案。