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A network meta-analysis on the efficacy of HER2-targeted agents in combination with taxane-containing regimens for treatment of HER2-positive metastatic breast cancer

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Abstract

Purpose

We performed a network meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of HER2-targeted agents in combination with taxanes and to identify the best strategy for HER2+ metastatic breast cancer (MBC).

Methods

Pubmed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched for randomized controlled trials that evaluated any taxanes+HER2-targeted agents in the treatment of HER2+ MBC. The primary outcome was overall survival (OS). The secondary outcomes included overall response rate (ORR) and progression-free survival (PFS).

Results

A total of 13 RCTs were eligible, involving 4941 patients and 10 regimens. The result showed that single-HER2-targeted agent+a taxane did improve the effect on ORR and PFS than taxane alone, but only trastuzumab+a taxane had a significant improvement in OS outcomes. Single-HER2-targeted agent (trastuzumab) combined with taxane-based doublets (taxane+carboplatin/capecitabine/doxorubicin/bevacizumab) showed no further benefit than trastuzumab+a taxane. Doublet-HER2-targeted agents combined with a taxane(trastuzumab+pertuzumab+a taxane) showed further improvement in ORR, PFS, and all OS outcomes than single-HER2-targeted agent+a taxane. Ranking analysis based on their P-scores suggested that trastuzumab+pertuzumab+a taxane was the best combination treatment for all the efficacy outcomes.

Conclusions

These findings demonstrate that combining two HER2-targeted agents (trastuzumab+pertuzumab) with a taxane is much more beneficial for the treatment of HER2+ MBC. Dual HER2-targeted agents combined with a taxane appears to be the preferred application of HER2+ MBC.

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Abbreviations

T:

Taxane

T+Tra:

Taxane+Trastuzumab

T+Lap:

Taxane+Lapatinib

T+Ner:

Taxane+Neratinib

T-DM1:

Trastuzumab emtansine

T+Tra+Car:

Taxane+Trastuzumab+Carboplatin

T+Tra+Cap:

Taxane+Trastuzumab+Capecitabine

T+Tra+Bev:

Taxane+Trastuzumab+Bevacizumab

T+Tra+NPLD:

Taxane+Trastuzumab+Nonpegylated liposomal doxorubicin

T+Tra+Per:

Taxane+Trastuzumab+Pertuzumab

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Funding

This study was funded by the Natural Science Foundation of China (81773828, 81273600), the Natural Science Foundation of Hebei Province (C2011206145, C2018206297), Key Project of Medical Science Research of Hebei Province (ZD20140163), the Research Project of Education Department, Hebei Province (ZD2016010),the Project Medical Science Research of Hebei Health and Family Planning Commission (20160402), and the Research Project of Hebei Health and Family Planning Commission (20160234).

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Author notes

  1. Bao-jie Xie and Li-na Zhu, both authors contributed equally to this work.

Authors and Affiliations

  1. Department of Radiology, The Fourth Hospital of Hebei Medical University, 12, Jiankang Road, Shijiazhuang, 050011, China

    Bao-jie Xie & Li-na Zhu

  2. Department of Cardiology, The Second Hospital of Hebei Medical University, 215, Heping West Road, Shijiazhuang, 050000, China

    Xin-shun Gu

  3. Department of Oncology, The First Hospital of Shijiazhuang, 36, Fanxi Road, Shijiazhuang, 050011, China

    Can Ma

  4. Department of Obstetrics and Gynecology Two Branch, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, 050031, China

    Ji-bin Li

  5. Department of Pharmacy, Hebei Childrenʼs Hospital, 133, Jianhua Street, Shijiazhuang, 050031, China

    Lei Dong

  6. Department of Pharmacology, Hebei Medical University, 361, Zhongshan East Road, Shijiazhuang, 050017, China

    Zhong-ning Zhu

  7. Department of Pathology, Hebei University of Chinese Medicine, 3, Xingyuan Road, Luquan, Shijiazhuang, 050200, China

    Tao Ding

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  1. Bao-jie Xie
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  2. Li-na Zhu
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Correspondence to Tao Ding or Xin-shun Gu.

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Xie, Bj., Zhu, Ln., Ma, C. et al. A network meta-analysis on the efficacy of HER2-targeted agents in combination with taxane-containing regimens for treatment of HER2-positive metastatic breast cancer. Breast Cancer 27, 186–196 (2020). https://doi.org/10.1007/s12282-019-01007-9

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  • DOI: https://doi.org/10.1007/s12282-019-01007-9

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