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Quantitative evaluation of the efficacy and safety profiles of two types of targeted inhibitors combined with endocrine therapy in ER+/HER2− metastatic breast cancer

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Abstract

Purpose

The aim of this study was to quantitatively compare the efficacy and safety of CDK4/6 inhibitors and PI3K/AKT/mTOR inhibitors for ER+/HER2− metastatic breast cancer.

Methods

A parametric survival function was used to analyze the time course of overall survival (OS) and progression-free survival (PFS). The objective response rate (ORR) and the incidence of any grade and grade 3–4 adverse events were summarized using the random-effects model of a single-arm meta-analysis.

Results

This study included 44 arms from 48 publications, with a total sample size of 7881 patients. Our study revealed that CDK4/6 inhibitors had a median OS of 40.7 months, a median PFS of 14.8 months, and an ORR of 40%, whereas PI3K/AKT/mTOR inhibitors had a median OS of 29.8 months, a median PFS of 8.3 months, and an ORR of 20%. Additionally, this study also found that the proportion of patients with visceral metastases and specific endocrine therapy used in combination significantly impact OS and PFS. In terms of adverse events, CDK4/6 inhibitors exhibited a relatively high incidence of hematological adverse events.

Conclusion

Our study provides solid quantitative evidence for the first-line recommendation of CDK4/6 inhibitors combined with endocrine therapy for ER+/HER2− metastatic breast cancer in clinical guidelines.

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Data availability

No datasets were generated or analysed during the current study.

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Acknowledgements

We thank all staff of the Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University.

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Authors and Affiliations

  1. School of Pharmacy, China Pharmaceutical University, Nan**g, China

    Meiyu Pan, Yinhui Liu & ** Yang

  2. Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nan**g, China

    ** Yang

  3. Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nan**g, China

    Yan Lin

  4. Department of Pharmacy, Nan**g Drum Tower Hospital, Affiliated Hospital of Medical School, Nan**g University, Nan**g, China

    Ruijuan Xu

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  1. Meiyu Pan
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  3. Yinhui Liu
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Contributions

Meiyu Pan and Yan Lin: conceptualization, data curation, formal analysis, investigation, writing—original draft, review, and editing. Meiyu Pan and Yan Lin contributed equally to this work. Yinhui Liu: software. Ruijuan Xu: conceptualization. ** Yang: conceptualization and methodology. ** Yang is the corresponding author of this article, and Ruijuan Xu is the co-corresponding author.

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Correspondence to Ruijuan Xu or ** Yang.

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Pan, M., Lin, Y., Liu, Y. et al. Quantitative evaluation of the efficacy and safety profiles of two types of targeted inhibitors combined with endocrine therapy in ER+/HER2− metastatic breast cancer. Eur J Clin Pharmacol (2024). https://doi.org/10.1007/s00228-024-03715-4

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