Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
ESMO Open. 2023 Jun;8(3):101216. doi: 10.1016/j.esmoop.2023.101216. Epub 2023 Apr 20.
Hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-positive (HER2+) breast cancer is a distinct subtype with different prognosis and response to treatment. HER2-targeted therapy is currently recommended for patients with HR+/HER2+ advanced breast cancer. However, there is debate over which drugs to add on the basis of HER2 blockade yield the optimal efficacy. This systematic review and network meta-analysis was conducted to solve the problem.
Eligible randomized controlled trials (RCTs) comparing different interventions in HR+/HER2+ metastatic breast cancer were included. The outcomes of interest included progression-free survival (PFS), overall survival (OS) and treatment-related adverse events (TRAEs). Pooled hazard ratios or odds ratios with credible intervals (CrIs) were calculated to estimate the predefined outcomes. The optimal therapeutics were identified by comparing the surface under the cumulative ranking curves (SUCRA).
Totally, 23 literatures of 20 RCTs were included. Regarding PFS, significant differences were detected between single or dual HER2 blockade plus endocrine therapy (ET) versus ET alone and dual HER2 blockade plus ET versus physician's choice. Trastuzumab, pertuzumab plus chemotherapy significantly improved PFS than trastuzumab plus chemotherapy (hazard ratio 0.69, 95% CrI 0.50-0.92). The SUCRA values suggested the relatively better efficacy of dual HER2-targeted therapy plus ET (86%-91%) than chemotherapy (62%-81%) in prolonging PFS and OS. The HER2 blockade-containing regimens showed similar safety profiles in eight documented TRAEs.
Prominent status of dual-targeted therapy for patients with HR+/HER2+ metastatic breast cancer was revealed. Compared with chemotherapy-containing regimens, the ET-containing ones showed better efficacy and similar safety profiles, which could be recommended in clinical practice.
激素受体阳性（HR+）和人表皮生长因子受体 2 阳性（HER2+）乳腺癌是一种具有不同预后和对治疗反应的独特亚型。目前建议 HR+/HER2+晚期乳腺癌患者使用 HER2 靶向治疗。然而，基于 HER2 阻断的哪种药物联合使用可获得最佳疗效仍存在争议。本系统评价和网络荟萃分析旨在解决这一问题。
纳入比较 HR+/HER2+转移性乳腺癌中不同干预措施的合格随机对照试验（RCT）。感兴趣的结局包括无进展生存期（PFS）、总生存期（OS）和治疗相关不良事件（TRAEs）。使用可信区间（CrI）计算合并的危险比或优势比来估计预设结局。通过比较累积排序曲线下面积（SUCRA）来确定最佳治疗方法。
共纳入 23 篇文献 20 项 RCT。关于 PFS，单药或双药 HER2 阻断加内分泌治疗（ET）与 ET 单药治疗和双药 HER2 阻断加 ET 与医生选择相比，差异有统计学意义。曲妥珠单抗、帕妥珠单抗联合化疗显著改善了 PFS，优于曲妥珠单抗联合化疗（风险比 0.69，95%CrI 0.50-0.92）。SUCRA 值表明，双 HER2 靶向治疗加 ET（86%-91%）在延长 PFS 和 OS 方面的疗效优于化疗（62%-81%）。在记录的八项 TRAEs 中，含 HER2 阻断的方案显示出相似的安全性特征。
本研究揭示了双靶向治疗在 HR+/HER2+转移性乳腺癌患者中的显著地位。与含化疗的方案相比，含 ET 的方案显示出更好的疗效和相似的安全性特征，可在临床实践中推荐使用。
