Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 1400 Pressler St, Unit 1411, Houston, TX, 77030, USA.
Section of Translational Breast Cancer, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
Breast Cancer Res Treat. 2019 Jan;173(1):1-9. doi: 10.1007/s10549-018-4969-6. Epub 2018 Sep 21.
Trastuzumab (H) with chemotherapy benefits patients with HER2+ breast cancer (BC); however, we lack head-to-head pairwise assessment of survival or cardiotoxicity for specific combinations. We sought to identify optimal combinations.
We searched PubMed, updated October 2017, using keywords "Breast Neoplasms/drug therapy," "Trastuzumab," and "Clinical Trial" and searched Cochrane Library. Our search included randomized trials of adjuvant H plus chemotherapy for early-stage HER2+ BC, and excluding trials of neoadjuvant therapy or without data to obtain hazard ratios (HRs) for outcomes. Following PRISMA guidelines, one investigator did initial search; two others independently confirmed and extracted information; and consensus with another investigator resolved disagreements. Before gathering data, we set outcomes of overall survival (OS), event-free survival (EFS), and severe cardiac adverse events (SCAEs). Analyzing 6 trials and 13,621 patients, we made direct and indirect comparisons using network meta-analysis on HR for OS or EFS and on odds ratio (OR) for SCAE; ranked therapy was done based on outcomes using p scores.
Compared with anthracycline-cyclophosphamide with taxane (ACT), ACT with concurrent H (ACT+H) showed best OS (HR 0.63, 95% confidence interval [CI] 0.55, 0.72), followed by taxane and carboplatin (TC) with concurrent H (TC+H) (HR 0.77, 95% CI 0.59, 1) and ACT with sequential H (ACT-H) (HR 0.85, 95% CI 0.68, 1.05). Pairwise comparisons showed statistically significant OS benefit for ACT+H over others; similar results for EFS. TC+H showed statistically significant lower SCAE risk compared to ACT+H (OR 0.13, 95% CI 0.03, 0.61).
Concurrent H with ACT or TC showed most clinical benefit for early-stage HER2+ BC; TC+H had lowest cardiotoxicity.
曲妥珠单抗（H）联合化疗可使 HER2+乳腺癌（BC）患者获益；然而，我们缺乏针对特定联合用药方案的生存获益或心脏毒性的头对头比较。我们旨在寻找最佳的联合用药方案。
我们使用关键词“Breast Neoplasms/drug therapy”、“Trastuzumab”和“Clinical Trial”在 PubMed 上进行了检索，检索日期截至 2017 年 10 月，并检索了 Cochrane 图书馆。我们的检索包括辅助治疗中早期 HER2+BC 患者接受曲妥珠单抗联合化疗的随机试验，排除新辅助治疗或无数据可获取生存结局风险比（HR）的试验。根据 PRISMA 指南，一名研究员进行了初步检索；另外两名研究员独立确认并提取信息；并与另一名研究员达成共识，以解决分歧。在收集数据之前，我们设定了总生存（OS）、无事件生存（EFS）和严重心脏不良事件（SCAE）的结局。通过对 6 项试验和 13621 例患者进行网络荟萃分析，我们比较了 OS 或 EFS 的 HR 以及 SCAE 的比值比（OR），并基于结局使用 p 评分进行了治疗排序。
与蒽环类环磷酰胺联合紫杉烷（ACT）相比，ACT 联合曲妥珠单抗（ACT+H）具有最佳的 OS（HR 0.63，95%置信区间 [CI] 0.55, 0.72），其次是紫杉烷联合卡铂（TC）联合曲妥珠单抗（TC+H）（HR 0.77，95% CI 0.59, 1）和 ACT 序贯曲妥珠单抗（ACT-H）（HR 0.85，95% CI 0.68, 1.05）。两两比较显示，ACT+H 组的 OS 获益明显优于其他组；EFS 也有类似结果。与 ACT+H 相比，TC+H 组的 SCAE 风险显著降低（OR 0.13，95% CI 0.03, 0.61）。
ACT 或 TC 联合曲妥珠单抗治疗早期 HER2+BC 可带来最大的临床获益；TC+H 的心脏毒性最低。
