吡咯替尼与曲妥珠单抗-美坦新偶联物（T-DM1）用于经曲妥珠单抗和紫杉烷预处理的HER2阳性转移性乳腺癌患者的疗效和安全性：一项贝叶斯网络荟萃分析

Efficacy and Safety of Pyrotinib Versus T-DM1 in HER2+ Metastatic Breast Cancer Patients Pre-Treated With Trastuzumab and a Taxane: A Bayesian Network Meta-Analysis.

作者信息

Liao Hao, Huang Wenfa, Liu Yaxin, Pei Wendi, Li Huiping

机构信息

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital and Institute, Beijing, China.

Department of Hematology-Oncology, International Cancer Center, Shenzhen University General Hospital, Shenzhen University Health Science Center, Shenzhen, China.

出版信息

Front Oncol. 2021 May 3;11:608781. doi: 10.3389/fonc.2021.608781. eCollection 2021.

PURPOSE

To compare the efficacy and safety between pyrotinib (Pyr) and trastuzumab emtansine (T-DM1) in pre-treated human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) patients.

METHODS

A comprehensive literature search of the PubMed, EMBASE, and Web of Science was performed in August 2020. Randomized clinical trials comparing the efficacy and safety between different anti-HER2 regimens in patients pre-treated with trastuzumab (Tra) and a taxane in metastatic settings (≤second-line treatment) were included. A fixed effects network meta-analysis based on the Bayesian inferential framework was conducted for progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and grade ≥3 adverse events (AEs). Values of surface under cumulative ranking probability curve (SUCRA) were calculated to offer a ranking of all regimens.

RESULTS

Twelve studies with 4,353 subjects were identified. Nine regimens were included into the network: T-DM1, lapatinib-capecitabine (Lap-Cap), Tra-Cap, Cap, neratinib (Ner), pertuzumab (Per)-Tra-Cap, Pyr-Cap, atezolizumab (Ate)-T-DM1, and Ner-Cap. For PFS, Pyr-Cap was more favorable than T-DM1 (hazard ratio, 95% confidence interval: 0.77, 0.70-0.86), Lap-Cap (0.64, 0.59-0.69), Tra-Cap (0.63, 0.56-0.70), Cap (0.50, 0.45-0.56), Ner (0.59, 0.51-0.69), Per-Tra-Cap (0.68, 0.59-0.79), and Ner-Cap (0.72, 0.64-0.81). For OS, Pyr-Cap showed further improvement than Lap-Cap (hazard ratio, 95% confidence interval: 0.71, 0.52-0.99), Cap (0.68, 0.49-0.96), and Ner (0.65, 0.45-0.94). For ORR, Pyr-Cap was significantly superior than Cap (odds ratio, 95% confidence interval: 7.87, 1.22-56.51). No significant difference was observed in grade ≥3 AEs among all the regimens. Pyr-Cap ranked in the highest in PFS, OS, ORR, and grade ≥3 AEs (SUCRA = 99.4, 89.7, 86.4, and 89.3%).

CONCLUSIONS

These results indicate that Pyr may be more effective than T-DM1 in HER2+ MBC patients pre-treated with Tra and a taxane. However, it may be associated with more grade ≥3 AEs.

目的

比较吡咯替尼（Pyr）与曲妥珠单抗-美坦新（T-DM1）在经治的人表皮生长因子受体2阳性（HER2+）转移性乳腺癌（MBC）患者中的疗效和安全性。

方法

2020年8月对PubMed、EMBASE和Web of Science进行了全面的文献检索。纳入了在转移性环境（≤二线治疗）中接受曲妥珠单抗（Tra）和紫杉烷预处理的患者中比较不同抗HER2方案疗效和安全性的随机临床试验。基于贝叶斯推理框架进行固定效应网络荟萃分析，以评估无进展生存期（PFS）、总生存期（OS）、总缓解率（ORR）和≥3级不良事件（AE）。计算累积排序概率曲线下面积（SUCRA）值以对所有方案进行排序。

结果

共纳入12项研究，4353名受试者。9种方案纳入网络：T-DM1、拉帕替尼-卡培他滨（Lap-Cap）、Tra-卡培他滨（Tra-Cap）、卡培他滨（Cap）、来那替尼（Ner）、帕妥珠单抗（Per）-Tra-卡培他滨、Pyr-卡培他滨、阿特珠单抗（Ate）-T-DM1和Ner-卡培他滨。对于PFS，Pyr-卡培他滨比T-DM1更具优势（风险比，95%置信区间：0.77，0.70-0.86）、Lap-Cap（0.64，0.59-0.69）、Tra-Cap（0.63，0.56-0.70）、Cap（0.50，0.45-0.56）、Ner（0.59，0.51-0.69）、Per-Tra-Cap（0.68，0.59-0.79）和Ner-卡培他滨（0.72，0.64-0.81）。对于OS，Pyr-卡培他滨比Lap-Cap（风险比，95%置信区间：0.71，0.52-0.99）、Cap（0.68，0.49-0.96）和Ner（0.65，0.45-0.94）有进一步改善。对于ORR，Pyr-卡培他滨显著优于Cap（优势比，95%置信区间：7.87，1.22-56.51）。所有方案中≥3级AE未观察到显著差异。Pyr-卡培他滨在PFS、OS、ORR和≥3级AE方面排名最高（SUCRA = 99.4%、89.7%、86.4%和89.3%）。