Abstract Objective Patients with hormone receptor positive (HR+), HER2- metastatic breast cancer frequently require radiation therapy (RT) in addition to systemic therapy for disease control and symptom management. CDK 4/6 inhibitors are increasingly used in the care of hormone positive breast cancers. Stereotactic body radiotherapy (SBRT), a form of very focused high dose radiation, is also increasingly used in the care of metastatic breast cancer. Limited data have reported on the safety of palliative RT with CDK4/6 inhibitors, with some reports demonstrating synergistic effects with potential for increased toxicity. The objective of our study is to assess toxicity among patients who received SBRT, stereotactic radiosurgery (SRS), or other high dose RT along with CDK 4/6 inhibitors for treatment of metastatic breast cancer. Methods Women with metastatic breast cancer who received SBRT, SRS, or other higher dose RT with CDK 4/6 inhibitors at any point in their treatment between 2013 and 2021 were retrospectively identified. Timing of radiation therapy, either before, during, or after CDK 4/6 inhibitor use was assessed, as well as the interval between the two treatments. Treatment sites for radiotherapy included lung/chest, spine, and brain metastases. Physician assessed adverse events were obtained through clinical follow up and graded using CTCAE v5. Local control and OS were reported. Results Twenty patients met study inclusion criteria. Patients received radiation therapy and CDK 4/6 inhibitors concurrently (within 7 days) [n=7, 35%], within 30 days (RT pre-CDK 4/6 inhibitor use) [n=3, 15%], and greater than 30 days (RT pre-CDK 4/6 inhibitor use [n=6, 30%] and RT post-CDK 4/6 inhibitor use [n=4, 20%]). Radiation treatment sites were spine [n=10, 55%], brain [n=6, 30%], and lung/chest wall [n=3, 15%]. Radiation doses were as follows: 60 Gy in 5 fractions [n=1, 5%], 50 Gy in 5 fractions [n=2, 10%], 55 Gy in 20 fractions (chest wall recurrence) [n=1, 5%], 35 Gy in 15 fractions [n=1, 5%], 30 Gy in 10 fractions [n=6, 30%], 30 Gy in 3 fractions [n= 4, 20%], 24 Gy in 1 fraction [n=3, 15%], 20 Gy in 5 fractions [n=2, 10%]. Palbociclib was used in 85% of patients [n=17] and abemaciclib in 15% [n=3]. Median follow up for surviving patients was 4.7 years [IQR: 2.5-6.8 years]. Local control was achieved in 85% of patients [n=17]. Median OS was 2.7 years [IQR: 0.1-6.8 years]. Grade 2 toxicity [n=9, 45%] and grade 3 toxicity [n=3, 15%] was reported across all three treatment areas, with grade 2 or 3 fatigue [n=7, 35%] being the most frequently reported toxicity. In the spine treatment group, 1 patient who had CDK 4/6 inhibitor use within 30 days of radiotherapy experienced a grade 3 vertebral compression fracture as well as grade 3 fatigue. In the lung/chest wall treatment group, the patient treated to 55 Gy in 20 fractions to the chest wall with concurrent use had grade 3 skin/wound toxicity requiring prolonged wound care before healing. In the intra-cranial SRS group, grade 3 fatigue was reported in 1 patient with concurrent use. Conclusion The use of CDK 4/6 inhibitors concurrently with or within 30 days of radiation therapy was generally well tolerated with limited grade 3 toxicity. Two of three reports of grade 3 toxicity occurred with concurrent treatment. Due to the potential radiosensitizing properties of CDK 4/6 inhibitors, it may be prudent to hold combined treatment when clinically feasible. Further study is needed to validate these results. Citation Format: Kiran Chauhan, Roman O. Kowalchuk, Allison E. Garda, Dean A. Shumway, Mark R. Waddle, Robert Mutter, Kimberly Corbin. Safety of stereotactic body radiation therapy, stereotactic radiosurgery, and other radiation therapy with use of CDK 4/6 inhibitors for hormone receptor positive (HR+), HER2- metastatic breast cancer: a retrospective cohort study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-05.
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Aug 1, 2024
Andrew D.C Alves 
Open Access