Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
Shanghai Medical College, Fudan University, Shanghai, China.
Front Immunol. 2022 Jun 30;13:919369. doi: 10.3389/fimmu.2022.919369. eCollection 2022.
The optimal (neo)adjuvant regimen for human epidermal growth factor receptor-2 (HER2)-positive breast cancer regarding survival outcomes remains unclear.
We 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.
Fifteen 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%.
Chemotherapy 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.
针对生存结局，人表皮生长因子受体 2（HER2）阳性乳腺癌的最佳（新）辅助治疗方案仍不明确。
我们系统地检索了 Web of Science、PubMed 和 Cochrane 中央对照试验注册库，以查找截至 2022 年 1 月比较不同抗 HER2 方案新辅助治疗的随机对照研究。主要终点是无病生存期（DFS）。我们使用贝叶斯统计模型结合直接和间接比较，并使用比值比（OR）汇总效应大小，并进行累积排序曲线下面积（SUCRA）曲线以估计各种方案的排名概率。对于生存结局，我们进行了两项平行分析，一项基于新辅助和辅助研究的数据，另一项专门针对辅助研究。所有统计均为双侧。
最终纳入了 15 项研究。对于 DFS，总体分析表明，HER2 阳性乳腺癌的前两种方案是化疗联合曲妥珠单抗加拉帕替尼，以及化疗联合曲妥珠单抗加帕妥珠单抗（SUCAR 分别为 81%和 79%），OR 为 0.99（95%CI，0.59 至 1.54）；针对辅助试验的平行分析表明，前两种方案是化疗联合曲妥珠单抗序贯奈拉替尼，以及化疗联合曲妥珠单抗加帕妥珠单抗（SUCRA 分别为 80%和 76%），OR 为 1.04（95%CI，0.63 至 1.73）。联合曲妥珠单抗和帕妥珠单抗的双靶治疗显示出最高的心脏事件风险，SUCRA 为 92%。
化疗联合曲妥珠单抗和帕妥珠单抗可能是提高 HER2 阳性乳腺癌生存率的最佳方案。然而，应注意这种双靶治疗的心脏毒性。
