Yu Liuwen, Fu Fangmeng, Li Jing, Huang Meng, Zeng Bangwei, Lin Yuxiang, Mei Qian, Lv Jinxing, Wang Chuan
Breast Surgery Ward, Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China.
Fujian Center for Disease Control and Prevention, Fuzhou, Fujian Province, China.
J Oncol. 2020 Mar 16;2020:5169278. doi: 10.1155/2020/5169278. eCollection 2020.
Although trastuzumab is the standard of care for patients with human epidermal growth factor receptor 2 (HER2)- positive early breast cancer (EBC), drug resistance and disease relapse occur. Therefore, we performed a meta-analysis to assess the efficacy and safety of trastuzumab-containing dual anti-HER2 therapy compared to trastuzumab alone.
A systematic search was performed to identify eligible randomized controlled trials (RCTs). Main outcomes including event-free survival/invasive disease-free survival (EFS/iDFS), overall survival (OS), and safety were considered.
Ten RCTs were included (15,284 patients). Significant improvements were observed in both EFS/iDFS (HR 0.86, =0.0003) and OS (HR 0.86, =0.02) with trastuzumab-based dual anti-HER2 therapy, especially in adjuvant treatment, while in the neoadjuvant setting, dual-targeted therapy also achieved a substantial pathological complete response (pCR) benefit (HR 1.34, =0.0002). Subgroup analysis revealed that the EFS/iDFS benefit was slightly higher with trastuzumab plus pertuzumab or plus neratinib than trastuzumab plus lapatinib, while OS benefit was significant with trastuzumab plus lapatinib, but there were no subgroup differences (interaction test, =0.80 and 0.24, resp.). In addition, EFS/iDFS benefit was unrelated to hormone receptor status but pronounced in the lymph node-positive (LN+) subgroup, which should be interpreted cautiously for lacking interaction (=0.18). Besides, patients receiving dual therapy, especially with the lapatinib-containing regimen, experienced more toxicity, but no increase in cardiotoxicity.
Despite being associated with more toxicity, trastuzumab-containing dual anti-HER2 therapy is superior to trastuzumab single agent for HER2-positive EBC independent of hormone receptor status. The correlation between survival and LN status needs further verification. Trastuzumab plus pertuzumab or plus neratinib is the preferred regimen with substantial efficacy and lower toxicity.
尽管曲妥珠单抗是人类表皮生长因子受体2（HER2）阳性早期乳腺癌（EBC）患者的标准治疗方案，但仍会出现耐药和疾病复发情况。因此，我们进行了一项荟萃分析，以评估含曲妥珠单抗的双联抗HER2治疗与单用曲妥珠单抗相比的疗效和安全性。
进行系统检索以确定符合条件的随机对照试验（RCT）。纳入主要结局，包括无事件生存/无浸润性疾病生存（EFS/iDFS）、总生存（OS）和安全性。
纳入了10项RCT（15284例患者）。基于曲妥珠单抗的双联抗HER2治疗在EFS/iDFS（风险比[HR]0.86，P=0.0003）和OS（HR 0.86，P=0.02）方面均有显著改善，尤其是在辅助治疗中；而在新辅助治疗中，双靶点治疗也实现了显著的病理完全缓解（pCR）获益（HR 1.34，P=0.0002）。亚组分析显示，曲妥珠单抗联合帕妥珠单抗或联合来那替尼的EFS/iDFS获益略高于曲妥珠单抗联合拉帕替尼，而曲妥珠单抗联合拉帕替尼的OS获益显著，但无亚组差异（交互检验，P分别为0.80和0.24）。此外，EFS/iDFS获益与激素受体状态无关，但在淋巴结阳性（LN+）亚组中较为明显，由于缺乏交互作用（P=0.18），对此应谨慎解读。此外，接受双联治疗的患者，尤其是含拉帕替尼方案的患者，毒性反应更多，但心脏毒性未增加。
尽管含曲妥珠单抗的双联抗HER2治疗毒性更大，但对于HER2阳性EBC患者，无论激素受体状态如何，其均优于曲妥珠单抗单药治疗。生存与LN状态之间的相关性需要进一步验证。曲妥珠单抗联合帕妥珠单抗或联合来那替尼是疗效显著且毒性较低的首选方案。
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