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Cyclin-Dependent Kinase 4/6 Inhibitors Combined With Radiotherapy for Patients With Metastatic Breast Cancer

  • Ivica Ratosa
    Correspondence
    Address for correspondence: Ivica Ratosa, MD, PhD, Division of Radiation Oncology, Institute of Oncology Ljubljana, Zaloska cesta 2, SI-1000 Ljubljana, Slovenia Fax: +386 1 5879 304
    Affiliations
    Division of Radiation Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia
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  • Miha Orazem
    Affiliations
    Division of Radiation Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia

    Department of Oncology, KU Leuven, Leuven, Belgium
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  • Erika Scoccimarro
    Affiliations
    Department of Experimental and Clinical Biomedical Sciences “M. Serio,” University of Florence, Florence, Italy

    Oncology Department, Radiation Oncology Unit, Azienda Ospedaliero Universitaria Careggi, Florence, Italy
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  • Mateja Steinacher
    Affiliations
    Department of Oncology, University Medical Centre Maribor, Maribor, Slovenia
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  • Luca Dominici
    Affiliations
    Department of Experimental and Clinical Biomedical Sciences “M. Serio,” University of Florence, Florence, Italy

    Oncology Department, Radiation Oncology Unit, Azienda Ospedaliero Universitaria Careggi, Florence, Italy
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  • Michele Aquilano
    Affiliations
    Department of Experimental and Clinical Biomedical Sciences “M. Serio,” University of Florence, Florence, Italy

    Oncology Department, Radiation Oncology Unit, Azienda Ospedaliero Universitaria Careggi, Florence, Italy
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  • Cecilia Cerbai
    Affiliations
    Department of Experimental and Clinical Biomedical Sciences “M. Serio,” University of Florence, Florence, Italy

    Oncology Department, Radiation Oncology Unit, Azienda Ospedaliero Universitaria Careggi, Florence, Italy
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  • Isacco Desideri
    Affiliations
    Department of Experimental and Clinical Biomedical Sciences “M. Serio,” University of Florence, Florence, Italy

    Oncology Department, Radiation Oncology Unit, Azienda Ospedaliero Universitaria Careggi, Florence, Italy
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  • Domen Ribnikar
    Affiliations
    Division of Medical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia
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  • Tanja Marinko
    Affiliations
    Division of Radiation Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia
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  • Lorenzo Livi
    Affiliations
    Department of Experimental and Clinical Biomedical Sciences “M. Serio,” University of Florence, Florence, Italy

    Oncology Department, Radiation Oncology Unit, Azienda Ospedaliero Universitaria Careggi, Florence, Italy
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  • Icro Meattini
    Affiliations
    Department of Experimental and Clinical Biomedical Sciences “M. Serio,” University of Florence, Florence, Italy

    Oncology Department, Radiation Oncology Unit, Azienda Ospedaliero Universitaria Careggi, Florence, Italy
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      Abstract

      Background

      The cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) represent the standard treatment for hormone receptor–positive, human epidermal growth factor receptor 2–negative metastatic breast cancer. Data about the balance between efficacy and toxicity of combined palliative radiotherapy (RT) and CDK4/6 inhibition are lacking.

      Patients and Methods

      We undertook a review of 46 patients with metastatic breast cancer on systemic treatment with CDK4/6i who underwent 62 metastases-directed RT. Clinical, laboratory, and RT treatment planning data were collected. Statistical analyses included Student t test, paired sample t test, and logistic regression modeling.

      Results

      Thirty patients (65.2%) received palbociclib, 15 (32.6%) received ribociclib, and one patient received abemaciclib (2.2%). Median total prescribed RT dose was 20 Gy (range, 8-63 Gy). Sites of RT were bone (n = 50; 80.7%), visceral (n = 7; 11.3%), or brain metastases (n = 3; 4.8%), as well as primary tumor of the breast (n = 2; 3.2%). Overall, the rates of grade 3 or higher adverse events (AEs) were 6.5%, 4.3%, 15.2%, and 23.9% before the start of RT, during RT, 2 and 6 weeks after RT completion, respectively. We found no correlation between dose distribution to organs at risk and the development of AEs. The local control rates for the entire cohort were 98% at 6 months and 90% at 12 months. Overall, pain relief (complete or partial) was experienced by 80% (24/30) of patients who initially reported pain at the treated metastatic site.

      Conclusion

      We observed a modest increase in the rates of grade 3 or higher AEs after combined RT and CDK4/6i, with maintained efficacy of concomitant RT.

      Keywords

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