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

• Published in: Journal of neuro-oncology 2019-09, Vol.144 (3), p.583-589
• Main Authors: Figura, Nicholas B., Potluri, Thrisha K., Mohammadi, Homan, Oliver, Daniel E., Arrington, John A., Robinson, Timothy J., Etame, Arnold B., Tran, Nam D., Liu, James K., Soliman, Hatem, Forsyth, Peter A., Sahebjam, Solmaz, Yu, H. Michael, Han, Hyo S., Ahmed, Kamran A.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aminopyridines - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Benzimidazoles - administration & dosage; Bevacizumab; Brain cancer; Brain Neoplasms - metabolism; Brain Neoplasms - secondary; Brain Neoplasms - therapy; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Clinical Study; Combined Modality Therapy; Cyclin-dependent kinase 4; Cyclin-Dependent Kinase 4 - antagonists & inhibitors; Cyclin-Dependent Kinase 6 - antagonists & inhibitors; Cyclin-dependent kinases; Disease Management; Female; Follow-Up Studies; Humans; Medicine; Medicine & Public Health; Metastases; Metastasis; Middle Aged; Monoclonal antibodies; Neurology; Neurotoxicity; Oncology; Piperazines - administration & dosage; Prognosis; Pyridines - administration & dosage; Radiation therapy; Radiosurgery - mortality; Receptor, ErbB-2 - metabolism; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Retrospective Studies; Steroid hormones; Survival; Survival Rate; Targeted cancer therapy; Toxicity
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1007/s11060-019-03260-6

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.