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CDK 4/6 inhibitors and stereotactic radiation in the management of hormone receptor positive breast cancer brain metastases

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Abstract

Purpose

Cyclin-dependent kinase (CDK) 4/6 inhibitors are becoming increasingly utilized in the setting of advanced, hormone receptor (HR+) positive breast cancer. Pre-clinical data suggests a potential synergy between radiation therapy (RT) and CDK4/6 inhibitors. We assessed clinical outcomes of patients treated at our institution with the use of CDK4/6 inhibitors and stereotactic radiation in the management of HR+ breast brain metastases.

Methods

A retrospective analysis of patients who received stereotactic radiotherapy for HR+ brain metastases within 6 months of CDK4/6 inhibitor administration was performed. The primary endpoint was neurotoxicity during or after stereotactic radiation. Secondary endpoints were local brain control, distant brain control, and overall survival (OS).

Results

A total of 42 lesions treated with stereotactic radiation in 15 patients were identified. Patients received either palbociclib (n = 10; 67%) or abemaciclib (n = 5; 33%). RT was delivered concurrently, before, or after CDK4/6 inhibitors in 18 (43%), 9 (21%), and 15 (36%) lesions, respectively. Median follow-up following stereotactic radiation was 9 months. Two lesions (5%) developed radionecrosis, both of which received four prior RT courses to the affected lesion prior to onset of radionecrosis and subsequently managed with steroids and bevacizumab. Six- and 12-month local control of treated lesions was 88% and 88%, while 6- and 12-month distant brain control was 61% and 39%, respectively. Median OS was 36.7 months from the date of brain metastases diagnosis.

Conclusions

Stereotactic radiation to breast brain metastases was well tolerated alongside CDK4/6 inhibitors. Compared to historical data, brain metastases control rates are similar whereas survival appears prolonged.

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr., Tampa, FL, 33612, USA

    Nicholas B. Figura, Thrisha K. Potluri, Homan Mohammadi, Daniel E. Oliver, Timothy J. Robinson, H. Michael Yu & Kamran A. Ahmed

  2. Department of Radiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA

    John A. Arrington

  3. Department of Neuro Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA

    Arnold B. Etame, Nam D. Tran, James K. Liu, Peter A. Forsyth & Solmaz Sahebjam

  4. Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA

    Hatem Soliman & Hyo S. Han

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  1. Nicholas B. Figura
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  2. Thrisha K. Potluri
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Correspondence to Kamran A. Ahmed.

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Conflicts of interest

Hyo S. Han declares that she has received a speaker’s honorarium from Lilly Pharmaceuticals; Peter A. Forsyth has received research funding and is on the advisory board for Pfizer.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (University of South Florida Institutional Review Board Pro00023399) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Figura, N.B., Potluri, T.K., Mohammadi, H. et al. CDK 4/6 inhibitors and stereotactic radiation in the management of hormone receptor positive breast cancer brain metastases. J Neurooncol 144, 583–589 (2019). https://doi.org/10.1007/s11060-019-03260-6

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