Supplementary data: A clinical systematic literature review of treatments among patients with advanced and/or metastatic human epidermal growth factor receptor 2 positive breast cancer

<b>These are peer-reviewed supplementary materials for the article '</b><b>A clinical systematic literature review of </b><b>treatments among patients with advanced </b><b>and/or metastatic human epidermal </b><b>growth factor receptor 2 positive breast </b><b>cancer</b><b>' published in the</b><b> </b><b><i>Journal of Comparative Effectiveness Research</i></b><b>.</b><b>Table A </b><b>1</b><b>: </b>Search Strategy for Embase<b>Table A </b><b>2</b><b>: </b>Search Strategy for MEDLINE<b>Table A </b><b>2</b><b>: </b>Search Strategy for Cochrane Central<b>Table A </b><b>3</b><b>: </b>Risk f of bias assessment for RCTs<b>Table A </b><b>4</b><b>: </b>Risk of bias assessment for observational studies<b>Aim:</b> This systematic literature review aims to summarize the efficacy/effectiveness of treatments, including eribulin (ERI)-based and anti-human epidermal growth factor receptor 2 (HER2) treatments in advanced/metastatic HER2+ breast cancer. <b>Methods: </b>Three databases from 2016 to September 2021 were searched for clinical trials and observational studies in patients receiving first-line (1L) standard of care (SOC), second-line (2L) SOC or third-line or subsequent lines (3L+). <b>Results: </b>2692 citations were screened, and 38 studies were included. Eleven studies were randomized-controlled trials (RCTs; 5 in 1L, 6 in 3L+), 6 were single-arm trials (5 in 1L, 1 in 3L+) and 21 were observational studies (13 in 1L, 6 in 2L, 4 in 3L+ [note that studies with subgroups for 1L, 2L, 3L+ are double-counted]). Longer overall survival (OS) was associated with 1L and 2L treatment, and for 3L+ studies that included ERI, ERI or trastuzumab (Tmab) + ERI led to longer OS than treatments of physician’s choice (median OS of 11, 10 and 8.9 months, respectively). Progression-free survival was 9 months in Tmab + pertuzumab (Pmab) + ERI, 4 months in mTmab + ERI and 3.3 months in ERI. <b>Conclusion: </b>Available treatments provide a wide range of efficacy. However, later lines lack standardization and conclusions on comparative effectiveness are limited by differing trial designs. Thus, the chance of prolonged survival with new agents warrants further research.

本材料为发表于《比较效果研究杂志》（*Journal of Comparative Effectiveness Research*）的文章《晚期和/或转移性人表皮生长因子受体2（human epidermal growth factor receptor 2, HER2）阳性乳腺癌患者治疗方案的临床系统综述》的经同行评审补充材料。
表A1：Embase数据库检索策略
表A2：MEDLINE数据库检索策略
表A2：Cochrane中心对照试验库检索策略
表A3：随机对照试验（randomized controlled trial, RCT）偏倚风险评估表
表A4：观察性研究偏倚风险评估表
**研究目的**：本系统综述旨在总结晚期/转移性HER2阳性乳腺癌患者的治疗方案疗效，包括以艾立布林（eribulin, ERI）为基础的治疗方案及抗HER2治疗方案。
**研究方法**：检索2016年至2021年9月期间的3个数据库，筛选接受一线（1L）标准治疗（standard of care, SOC）、二线（2L）标准治疗或三线及以上（3L+）治疗的患者相关临床试验与观察性研究。
**研究结果**：共筛选2692条引文，最终纳入38项研究。其中11项为随机对照试验（RCT，其中1L亚组5项、3L+亚组6项），6项为单臂试验（1L亚组5项、3L+亚组1项），21项为观察性研究（1L亚组13项、2L亚组6项、3L+亚组4项；注：包含1L、2L、3L+亚组的研究将被重复计数）。一线与二线治疗可延长总生存期（overall survival, OS）；在纳入艾立布林的3L+研究中，艾立布林单药或曲妥珠单抗（trastuzumab, Tmab）联合艾立布林的总生存期均长于医师选择方案（中位总生存期分别为11个月、10个月与8.9个月）。曲妥珠单抗联合帕妥珠单抗（pertuzumab, Pmab）联合艾立布林的无进展生存期为9个月，曲妥珠单抗类似物（mTmab）联合艾立布林为4个月，艾立布林单药为3.3个月。
**研究结论**：现有治疗方案展现出广泛的疗效谱，但后线治疗缺乏标准化方案，且比较疗效相关结论受试验设计差异限制。因此，新型药物带来延长生存期的可能性值得开展进一步研究。