HER2阳性不可切除、局部晚期或转移性乳腺癌患者在先前使用曲妥珠单抗治疗后的HER2靶向治疗方案：一项随机对照试验的网状Meta分析
HER2-targeted regimens after prior trastuzumab for patients with HER2-positive unresectable, locally advanced or metastatic breast cancer: a network meta-analysis of randomized controlled trials.
作者信息
Li Xinghui, Wu Songwen, Zhang Lijie, Zhu Ji, Xu Binghe
机构信息
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
出版信息
Ann Transl Med. 2020 Dec;8(24):1634. doi: 10.21037/atm-20-5149.
BACKGROUND
Several human epidermal growth factor receptor 2 (HER2)-targeted regimens (anti-HER2 target agent combined chemotherapy) have been introduced for the treatment of HER2-positive locally advanced or metastatic breast cancer progressed after trastuzumab. We therefore conducted a network meta-analysis to compare and rank HER2-targeted regimens in this population after trastuzumab therapy.
METHODS
The electronic databases of PubMed, EmBase, Cochrane Central Register of Controlled Trials, and the websites of http://clinicaltrials.gov/ (US NIH) were systematically searched for published and unpublished randomized controlled trials (RCTs) from their inception to October, 2020. Nine treatment regimens were eligible to be included in this analysis. The primary outcomes were overall response rate (ORR), progression-free survival (PFS) and overall survival (OS), while the secondary outcomes were grade ≥3 adverse events.
RESULTS
A total of 2,104 citations were identified and 12 RCTs comprising 3,769 patients were selected for final analysis. For HER2 positive unresectable, locally advanced or metastatic patients progressed after trastuzumab therapy pyrotinib plus capecitabine ranked the highest surface under the cumulative ranking area (SUCRA) in PFS, ORR and its SUCRA in OS was higher than Trastuzumab emtansine (T-DM1). T-DM1 plus atezolizumab, pyrotinib plus capecitabine, and pertuzumab plus trastuzumab plus capecitabine had comparable SUCRA in OS (76.1% 74.5% 71.2%). Six of included studies reported any grade ≥3 adverse events, the prevalence of any grade ≥3 adverse events in lapatinib plus capecitabine (353/683), T-DM1 (213/558), trastuzumab plus capecitabine (130/218), pertuzumab plus trastuzumab plus capecitabine (118/228), pyrotinib plus capecitabine (220/384), T-DM1 plus atezolizumab (43/132) and capecitabine (24/94) were 51.7%, 38.2%, 59.6%, 51.8%, 57.3%, 32.6% and 25.5%, respectively. Specific adverse event characteristics related to different HER2-targeted regimens need to be well known ahead and managed during the therapy.
CONCLUSIONS
The results indicated that for HER2 positive breast cancer with previous trastuzumab therapy pyrotinib plus capecitabine was probably more efficacious in PFS and ORR. T-DM1 plus atezolizumab, pyrotinib plus capecitabine and pertuzumab plus trastuzumab plus capecitabine have comparable effect on OS improvement and all of them were likely better than T-DM1. The risk of grade ≥3 adverse events for specific treatment regimens were also provided.
背景
已引入几种人表皮生长因子受体2（HER2）靶向治疗方案（抗HER2靶向药物联合化疗）用于治疗曲妥珠单抗治疗后进展的HER2阳性局部晚期或转移性乳腺癌。因此，我们进行了一项网状荟萃分析，以比较和排序曲妥珠单抗治疗后该人群中HER2靶向治疗方案。
方法
系统检索PubMed、EmBase、Cochrane对照试验中央注册库的电子数据库以及http://clinicaltrials.gov/（美国国立卫生研究院）网站，以查找从创建到2020年10月发表和未发表的随机对照试验（RCT）。九种治疗方案符合纳入本分析的条件。主要结局为总缓解率（ORR）、无进展生存期（PFS）和总生存期（OS），次要结局为≥3级不良事件。
结果
共识别出2104条引文，选择12项RCT（共3769例患者）进行最终分析。对于HER2阳性不可切除、局部晚期或转移性患者，曲妥珠单抗治疗后进展，吡咯替尼联合卡培他滨在PFS的累积排序曲线下面积（SUCRA）排名最高，其OS的SUCRA高于曲妥珠单抗-美坦新（T-DM1）。T-DM1联合阿替利珠单抗、吡咯替尼联合卡培他滨以及帕妥珠单抗联合曲妥珠单抗联合卡培他滨在OS方面具有可比的SUCRA（分别为76.1%、74.5%、71.2%）。纳入的研究中有六项报告了任何≥3级不良事件，拉帕替尼联合卡培他滨（353/683）、T-DM1（213/558）、曲妥珠单抗联合卡培他滨（130/218）、帕妥珠单抗联合曲妥珠单抗联合卡培他滨（118/228）、吡咯替尼联合卡培他滨（220/384）、T-DM1联合阿替利珠单抗（43/132）和卡培他滨（24/94）中任何≥3级不良事件的发生率分别为51.7%、38.2%、59.6%、51.8%、57.3%、32.6%和25.5%。与不同HER2靶向治疗方案相关的特定不良事件特征需要提前充分了解并在治疗期间进行管理。
结论
结果表明，对于既往接受曲妥珠单抗治疗的HER2阳性乳腺癌，吡咯替尼联合卡培他滨在PFS和ORR方面可能更有效。T-DM1联合阿替利珠单抗、吡咯替尼联合卡培他滨以及帕妥珠单抗联合曲妥珠单抗联合卡培他滨在改善OS方面具有可比的效果，且所有这些方案可能都优于T-DM1。还提供了特定治疗方案的≥3级不良事件风险。
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