Efficacy of radiotherapy for bone metastasis in breast cancer patients treated with cyclin-dependent kinase 4/6 inhibitors

Background: In patients diagnosed with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer, bone metastases emerge as the primary site of significant tumor burden. Cyclin-dependent kinase 4/6 (CDK4/6i) inhibitors are the gold standard in this clinical scenario, while radiotherapy (RT) represents a valuable addition. However, data on the efficacy of this combination remain scarce. We aimed to evaluate efficacy of RT in bone metastatic breast cancer patients treated with CDK4/6 inhibitors. Materials and methods: 398 patients (pts) with ER-positive HER2-negative breast cancer with bone metastases treated with CDK4/6i between 2018-2024 were analyzed. A total of 114 pts received 177 bone RT concurrently with CDK4/6i or within 6 months before CDK4/6i initiation, including 34 courses of stereotactic-body RT and 143 courses of conventional RT. Results: The median progression-free survival (PFS) in pts who received bone RT was 31.0 months, compared to 26.3 months in pts without bone RT. The 2-y PFS for pts with bone RT was 57.1 % [95 % CI: 46.3-66.6 %] vs. 53.2 % [95 % CI: 46.3-59.6 %] for patients without bone RT (p = 0.51). The median overall survival (OS) for pts who received bone RT was 49.1 months, compared to 40.5 months for pts without bone RT. The 3-y OS for pts with bone RT was 63.7 % [95 % CI: 51.5-73.5 %] vs. 55.0 % [95 % CI 46.6-62.6 %] for pts without bone RT (p = 0.50). The 3-y local control for irradiated patients was 86.9 % [95 % CI 72.2-94.1 %]. Conclusions: In this study, we present the largest cohort published to date of breast cancer patients who received CDK4/6i alongside bone-directed RT. Although the observed differences in survival were not statistically significant, RT remains a viable treatment modality in metastatic breast cancer in some patients.