Radiotherapy with Cyclin-Dependent Kinase 4/6 Inhibitors: A Multi-institutional Safety and Toxicity Study

To investigate radiotherapy (RT) toxicity when given with Cyclin-Dependent Kinase 4/6 inhibitors (CDK4/6i) compared to RT alone.We conducted a retrospective cohort study of patients with hormonal receptor-positive and human epidermal growth factor-2 negative metastatic breast cancer treated with RT at four cancer centers in Alberta, Canada between 2016 and 2020. Toxicity in patients treated with RT within 30 days of initiating to discontinuing CDK4/6i (RT+CDK4/6i) was compared to toxicity of RT in CDK4/6i naïve patients (RT alone). The primary outcome was acute grade (G) II or higher, non-hematological toxicity within 30 days of RT. We also explored toxicity based on the timing of RT (prior, concurrent, post) in relation to CDK4/6i. Propensity score matching was applied to create comparable cohorts. A generalized linear mixed model was used to evaluate factors associated with acute toxicity.132 patients (220 RT sites) in the RT+CDK4/6i and 53 patients (93 RT sites) in RT alone were eligible. The rate of acute GII or higher non-hematological toxicity was 11.5% vs. 7%, respectively (p=0.439), and acute GIII or higher non-hematological toxicity was 3.7% vs. 0%, respectively (p=0.151). Acute toxicity in RT+CDK4/6i group was mainly observed when RT was given concurrently (67%) with most of the GIII toxicity recorded. After propensity score matching, the association of acute toxicity with RT+CDK4/6i vs. RT alone was not significant on multivariable analysis, Odds Ratio 3.13 (95% confidence interval: 0.74 - 13.2; p=0.121).We did not observe a significant association between CDK4/6i use and acute, GII or higher, non-hematological toxicity, in women with metastatic breast cancer receiving palliative RT. Given the findings of GIII toxicity, caution is advised whenever CDK4/6i is given concurrently with RT.