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

These are peer-reviewed supplementary materials for the article 'A clinical systematic literature review of treatments among patients with advanced and/or metastatic human epidermal growth factor receptor 2 positive breast cancer' published in the Journal of Comparative Effectiveness Research.
Table A 1: Search Strategy for EmbaseTable A 2: Search Strategy for MEDLINETable A 2: Search Strategy for Cochrane CentralTable A 3: Risk f of bias assessment for RCTsTable A 4: Risk of bias assessment for observational studiesAim: 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. Methods: 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+). Results: 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. Conclusion: 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《比较疗效研究杂志》的《晚期和/或转移性人表皮生长因子受体2（HER2）阳性乳腺癌患者治疗方案临床系统综述》一文的同行评议补充材料。
表A1：Embase数据库检索策略
表A2：MEDLINE数据库检索策略
表A2：Cochrane中心对照试验注册库（Cochrane Central）检索策略
表A3：随机对照试验（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和/或转移性HER2阳性乳腺癌患者的治疗方案疗效，包括以艾立布林（ERI）为基础的治疗方案及抗HER2治疗方案。
研究方法：本研究检索了2016年至2021年9月期间的3个数据库，纳入接受一线（1L）标准治疗（SOC）、二线（2L）标准治疗或三线及以上（3L+）治疗的患者相关的临床试验与观察性研究。
研究结果：本研究共筛选2692条文献引文，最终纳入38项研究。其中11项为随机对照试验（RCT）：一线治疗5项、三线及以上治疗6项；6项为单臂试验：一线治疗5项、三线及以上治疗1项；21项为观察性研究：一线治疗13项、二线治疗6项、三线及以上治疗4项（注：包含一线、二线、三线及以上亚组的研究存在重复计数情况）。一线与二线治疗可延长患者总生存期（OS）；在纳入艾立布林的三线及以上治疗研究中，艾立布林单药或曲妥珠单抗（Tmab）联合艾立布林的治疗方案较医师选择的治疗方案可获得更长的总生存期（中位OS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（Pmab）联合艾立布林方案的无进展生存期为9个月，曲妥珠单抗生物类似药（mTmab）联合艾立布林方案为4个月，艾立布林单药方案为3.3个月。
研究结论：现有治疗方案的疗效覆盖范围较广，但后线治疗缺乏统一标准，且不同试验设计导致比较疗效相关结论的说服力受限。因此，新型药物延长患者生存期的潜力有待进一步研究探索。