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. 2023 Feb 20:13:1003565.
doi: 10.3389/fonc.2023.1003565. eCollection 2023.

Treatment options for patients with human epidermal growth factor 2-positive breast cancer brain metastases: A systematic review and meta-analysis

Xingfa Huo  1   2 , Guoshuang Shen  1 , Tianzhuo Wang  1 , Jinming Li  1 , Qiqi Xie  1 , Zhen Liu  1 , Miaozhou Wang  1 , Fuxing Zhao  1 , Dengfeng Ren  1 , Jiuda Zhao  1
Affiliations

Treatment options for patients with human epidermal growth factor 2-positive breast cancer brain metastases: A systematic review and meta-analysis

Xingfa Huo et al. Front Oncol. .

Abstract

Introduction: Many systemic treatment options are available for patients with human epidermal growth factor 2 (HER2)-positive breast cancer brain metastases. However, it is unclear which pharmacological treatment option is the most beneficial.

Methods: We searched databases, such as PubMed, Embase, and Cochrane Library, and conference abstracts according to keywords. We extracted progression-free survival (PFS), overall survival (OS) data, and overall response rate (ORR) from randomized controlled trials and single-arm studies of HER2-positive breast cancer brain metastasis treatment for meta-analysis and analyzed different drug-related adverse events (AEs).

Results: Three randomized controlled trials and seven single-arm clinical studies with 731 patients with HER2-positive brain metastases from breast cancer involving at least seven drugs were included. In randomized controlled trials, our results showed that trastuzumab deruxtecan significantly improved PFS and OS in patients and was superior to other drug regimens. In the single-arm study, the ORR was more pronounced for the trastuzumab deruxtecan and pyrotinib plus capecitabine regimens (ORR, 73.33%; 95% confidence intervals [CI], 44.90%-92.21%; ORR, 74.58%; 95% CI, 61.56%-85.02%, respectively). We found that the main AEs of antibody-drug conjugate (ADC) were nausea and fatigue, while the main AE of small-molecule tyrosine kinase inhibitor (TKI) drugs and large monoclonal antibodies was diarrhea.

Conclusions: Trastuzumab deruxtecan was shown to be the most significant in improving survival in patients with HER2-positive breast cancer brain metastases in network meta-analysis, and in single-arm study, patients with HER2-positive breast cancer brain metastases treated with trastuzumab deruxtecan and pyrotinib plus capecitabine regimen had the highest ORR. The main AEs associated with ADC, large monoclonal antibodies, and TKI drugs were nausea, fatigue, and diarrhea, respectively.

Keywords: HER2; brain metastases; breast cancer; meta-analysis; treatment.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Network meta-analysis of progression-free survival.
Figure 2
Figure 2
League table of network meta-analysis of the four anti-HER2 regimens. Red represents a statistically significant difference (P < 0.05). HER2, Human Epidermal Growth Factor 2. Trastuzumab deruxtecan, DS-8201; Trastuzumab emtansine, T-DM1.
Figure 3
Figure 3
The ranking of PFS in anti-HER2 treatment regimens. (A) Individual ranking plots of PFS between different anti-HER2 treatment regimens. (B) The results of SUCRA for PFS between different anti-HER2 treatment regimens. PFS, progression-free survival; HER2, human epidermal growth factor 2; SUCRA, cumulative ranking curve.
Figure 4
Figure 4
Forest plot of progression-free survival and overall survival in randomized controlled trials.
Figure 5
Figure 5
Forest plot of the overall response rate in single-arm studies.
Figure 6
Figure 6
Adverse events associated with anti-Human Epidermal Growth Factor 2 therapeutic agents.
See this image and copyright information in PMC

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