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CDK4/6 inhibitors: The Devil is in the Detail

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Abstract

Purpose of review

Update on the most recent clinical evidence on CDK4/6 inhibitors (CDK4/6i) in the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor (HER)2-negative breast cancer.

Recent findings

Over the past decade, CDK4/6i have become part of the standard of care treatment of patients with both metastatic and high-risk early HR + /HER2- breast cancers. The three available CDK4/6i (palbociclib, ribociclib and abemaciclib) have been extensively studied in combination with endocrine therapy (ET) in metastatic breast cancer (mBC) with consistent prolongation of progression free survival; however, ribociclib has emerged as the preferred first line agent in mBC given overall survival benefit over endocrine monotherapy. In early BC, abemaciclib is the only currently approved agent while ribociclib has early positive clinical trial data. Toxicities and financial burden limit the use of CDK4/6i in all patients and resource-poor settings, and optimal timing of their use in mBC remains unclear.

Summary

There is considerable evidence for the use of CDK4/6i in metastatic and early HR + /HER2- breast cancer, but knowledge gaps remain, and further research is necessary to better define their optimal use.

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  1. Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA

    Tara Magge, Sneha Rajendran, Adam M. Brufsky & Julia Foldi

  2. Breast Medical Oncology, Magee Women’s Hospital, University of Pittsburgh Medical Center, 300 Halket Street, Suite 3524, Pittsburgh, PA, 15213, USA

    Julia Foldi

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TM and SR wrote the initial manuscript draft. JF wrote the final manuscript draft and all authors reviewed it.

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Tara Magge, Sneha Rajendran and Julia Foldi have no conflicts of interest to declare. Adam Brufsky: consultant for Astrazeneca, Pfizer, Novartis, Lilly, Genentech/Roche, SeaGen, Daiichi Sankyo, Merck, Agendia, Sanofi, Puma, Myriad, Gilead, GE.

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Magge, T., Rajendran, S., Brufsky, A.M. et al. CDK4/6 inhibitors: The Devil is in the Detail. Curr Oncol Rep (2024). https://doi.org/10.1007/s11912-024-01540-7

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