Clinical Value of Bone Radiotherapy in a Prospective Cohort of Metastatic Breast Cancer Treated with Anti-CDK4/6

Abstract

Background: CDK4/6 inhibitor plus ET is a standard treatment for advanced HR+ BC. This study evaluates the efficacy and safety of CDK4/6 inhibitors with concurrent RT (SBRT and non-SBRT) in terms of pain, analgesic therapy changes, toxicities, and net clinical benefit (NCB). Methods: BC patients with bone metastases treated with RT and CDK4/6 inhibitor in the prospective observational COMBART study were analyzed. Pain was measured with the NRS. The NCB was defined by pain reduction (NRS), toxicity, and treatment changes. Adverse events (AEs) were graded per CTCAE v5.0. Statistical tests included chi-square and t-test. Results: Forty patients were treated with CDK4/6 inhibitor (palbociclib 30.8%, ribociclib 51.3%, abemaciclib 17.9%) and RT (131 lesions; 100 SBRT, 31 non-SBRT). The mean NRS score dropped from 3.52 (pre-treatment) to 1.31 (post-treatment) (p < 0.001), with better outcomes for patients treated with moderate hypofractionation (58.6% vs. 39.9% pain relief, p = 0.016). Pain relief was independent of the type of CDK4/6 inhibitor used (p = NS). Analgesic reduction was most common with palbociclib (35.4%, p = 0.001). Eight toxicities (grade 1-2) were reported. The NCB was 0.6 overall, higher with non-SBRT (0.74 vs. 0.52). Conclusions: RT plus CDK4/6 inhibitor, especially with moderate hypofractionation, significantly reduced pain with manageable toxicity. Analgesic therapy can often continue without stopping CDK4/6 inhibitor.

Keywords: CDK4/6 inhibitors; bone metastases; radiotherapy.