J Cancer 2021; 12(6):1687-1697. doi:10.7150/jca.51845

Research Paper

Efficacy of second-line treatments for patients with advanced human epidermal growth factor receptor 2 positive breast cancer after trastuzumab-based treatment: a systematic review and bayesian network analysis

Fei Chen, Naifei Chen, Zheng Lv, Lingyu Li, Jiuwei Cui

Cancer Center, the First Hospital of Jilin University, Changchun, China.

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Citation:
Chen F, Chen N, Lv Z, Li L, Cui J. Efficacy of second-line treatments for patients with advanced human epidermal growth factor receptor 2 positive breast cancer after trastuzumab-based treatment: a systematic review and bayesian network analysis. J Cancer 2021; 12(6):1687-1697. doi:10.7150/jca.51845. Available from https://www.jcancer.org/v12p1687.htm

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Abstract

Purpose: Different second-line treatments of patients with trastuzumab-resistant human epidermal growth factor receptor 2 (HER2) positive breast cancer were examined in randomized controlled trials (RCTs). A network meta-analysis is helpful to evaluate the comparative survival benefits of different options.

Methods: We performed a bayesian network meta-analysis using R-4.0.0 software and fixed consistency model to compare the progression free survival (PFS) and overall survival (OS) benefits of different second-line regimens.

Results: 13 RCTs (19 publications, 4313 patients) remained for qualitative synthesis and 12 RCTs (17 publications, 4022 patients) were deemed eligible for network meta-analysis. For PFS, we divided network analysis into two parts owing to insufficient connections among treatments. The first part involved 8 treatments in 9 studies and we referred it as PFS (#1). Amid the following 8 interventions: pyrotinib + capecitabine, T-DM1 + atezolizumab, pertuzumab + trastuzumab + capecitabine, T-DM1, trastuzumab + capecitabine, lapatinib + capecitabine, neratinib, and capecitabine, we found consistent benefits between the first three interventions; moreover, pyrotinib + capecitabine was most likely to be associated with the best benefits; capecitabine monotherapy was associated with the worst PFS. The second part included 3 treatments in 2 studies and we referred it as PFS (#2): everolimus + trastuzumab + vinorelbine had better PFS benefits versus trastuzumab + vinorelbine and afatinib + vinorelbine. For OS, we analyzed 7 treatments in 7 studies, and observed T-DM1 + atezolizumab, pertuzumab + trastuzumab + capecitabine, and T-DM1 had similar effectiveness, and the first had the highest probability to yield the longest OS; capecitabine or neratinib alone yielded the worst OS benefits.

Conclusions: Our work comprehensively summarized and analyzed current available RCT-based evidence of the second-line treatments for trastuzumab-treated, HER2-positive, advanced breast cancer. These results provide clinicians and oncologists meaningful references for clinical drug administration and the development of novel effective therapies.

Keywords: human epidermal growth factor receptor 2 positive, metastatic breast cancer, advanced breast cancer, second-line treatment, network meta-analysis