Radiation Therapy With Cyclin-Dependent Kinase 4/6 Inhibitors: A Multi-institutional Safety and Toxicity Study

Abstract

Our purpose was to investigate radiation therapy (RT) toxicity when given with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) compared with 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 4 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 with toxicity of RT in CDK4/6i-naïve patients (RT alone). The primary outcome was acute grade (G) 2 or higher, nonhematological 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. One hundred thirty-two patients (220 RT sites) in the RT+CDK4/6i and 53 patients (93 RT sites) in RT alone were eligible. The rate of acute G2 or higher nonhematological toxicity was 11.5% versus 7%, respectively (P=.439), and acute G3 or higher nonhematological toxicity was 3.7% versus 0%, respectively (P=.151). Acute toxicity in RT+CDK4/6i group was mainly observed when RT was given concurrently (67%), with most of the G3 toxicity recorded. After propensity score matching, the association of acute toxicity with RT+CDK4/6i versus RT alone was not significant on multivariable analysis (odds ratio, 3.13; 95% confidence interval, 0.74-13.2; P=.121). We did not observe a significant association between CDK4/6i use and acute G2 or higher nonhematological toxicity in women with metastatic breast cancer receiving palliative RT. Given the findings of G3 toxicity, caution is advised whenever CDK4/6i is given concurrently with RT.