DataSheet_1_Determining the Optimal (Neo)Adjuvant Regimen for Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Regarding Survival Outcome: A Network Meta-Analysis.zip

BackgroundThe optimal (neo)adjuvant regimen for human epidermal growth factor receptor-2 (HER2)-positive breast cancer regarding survival outcomes remains unclear.MethodsWe searched Web of Science, PubMed, and the Cochrane Central Register of Controlled Trials systematically to find out randomized controlled studies, up to January 2022, that compared different anti-HER2 regimens in the (neo)adjuvant setting. The primary endpoint was disease-free survival (DFS). We used a Bayesian statistical model to combine direct and indirect comparisons and used odds ratios (ORs) to pool effect sizes and performed the surface under the cumulative ranking area (SUCRA) curves to estimate the ranking probabilities of various regimens. For survival outcomes, we performed two parallel analyses, one based on data from both neoadjuvant and adjuvant studies and the other specific to adjuvant studies. All statistics were two-sided.ResultsFifteen studies were finally enrolled. Regarding DFS, the overall analysis indicated that the top two regimens for HER2-positive breast cancer were chemotherapy plus trastuzumab with lapatinib, and chemotherapy plus trastuzumab with pertuzumab (SUCAR of 81% and 79%, respectively), with the OR of 0.99 [95% confidence interval (CI), 0.59 to 1.54]; the parallel analysis specific to adjuvant trials indicated that the top two regimens were chemotherapy plus trastuzumab with sequential neratinib, and chemotherapy plus trastuzumab with pertuzumab (SUCRA of 80% and 76%, respectively), with the OR of 1.04 (95% CI, 0.63 to 1.73). The dual-target therapy that combines trastuzumab and pertuzumab showed the highest risk of inducing cardiac events, with an SUCRA of 92%.ConclusionsChemotherapy plus trastuzumab and pertuzumab might be the optimal regimen for HER2-positive breast cancer in improving the survival rate. However, the cardiotoxicity of this dual-target therapy should be taken care of.

背景：针对人表皮生长因子受体-2（HER2）阳性的乳腺癌患者，关于最佳（新）辅助治疗方案以改善生存结果的问题尚无明确答案。方法：本研究系统性地检索了Web of Science、PubMed以及Cochrane中央注册的对照试验数据库，直至2022年1月，以寻找比较不同抗HER2治疗方案在（新）辅助治疗设置中的随机对照研究。主要终点为无病生存期（DFS）。本研究采用贝叶斯统计模型结合直接和间接比较，并使用优势比（OR）来汇总效应量，并通过累积排名面积下界（SUCRA）曲线估计各种治疗方案的排序概率。针对生存结果，我们进行了两项平行分析，一项基于新辅助和辅助治疗研究的数据，另一项则专注于辅助治疗研究。所有统计检验均为双尾检验。结果：最终纳入了15项研究。关于DFS，总体分析表明，对于HER2阳性乳腺癌而言，前两种最佳治疗方案分别为化疗联合曲妥珠单抗与拉帕替尼，以及化疗联合曲妥珠单抗与帕妥珠单抗（SUCRA分别为81%和79%），优势比为0.99[95%置信区间（CI）为0.59至1.54]；针对辅助治疗研究的平行分析显示，前两种最佳治疗方案为化疗联合曲妥珠单抗与依维莫司序贯治疗，以及化疗联合曲妥珠单抗与帕妥珠单抗（SUCRA分别为80%和76%），优势比为1.04（95% CI，0.63至1.73）。曲妥珠单抗与帕妥珠单抗联合的双靶点治疗显示出最高的心脏事件风险，SUCRA为92%。结论：化疗联合曲妥珠单抗与帕妥珠单抗可能成为提高HER2阳性乳腺癌患者生存率的最佳治疗方案。然而，此双靶点治疗的心脏毒性问题亦需予以关注。