Safety and feasibility of CDK4/6 inhibitors treatment combined with radiotherapy in patients with HR-positive/HER2-negative breast cancer. A systematic review and meta-analysis

Background and PurposeThe addition of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) to endocrine therapy in hormone receptor-positive (HR+) human epidermal growth factor 2-negative (HER2-) breast cancer has led to practice-changing improvements in overall survival. However, there are conflicting data concerning the safety of CDK4/6i combination with radiotherapy, and no consensus guidelines exist to guide practice. We conducted a meta-analysis to assess the safety and feasibility of CDK4/6i treatment with radiotherapy.Materials and MethodsA comprehensive search was performed in PubMed/MEDLINE, Web of Science, and Scopus, for studies in advanced/metastatic breast cancer receiving CDK4/6i and radiotherapy with the provided safety data on the occurrence of toxicity. The main outcomes were safety (grade 3-5 adverse events), CDK 4/6i dose reduction, and the discontinuation rate due to toxicity.ResultsFifteen studies comprising 1133 patients with HR+/HER2- breast cancer patients were included. Among them, 617 pts received CDK4/6i and radiotherapy; the median follow-up was 17.0 months (IQR 9.2 – 18.0), and the median age was 58.8 years (IQR 55.5 - 62.5). The pooled prevalence of severe hematologic toxicity was 29.4% (95% CI 14.0% – 47.4%; I2 = 93%; τ2 = 0.084; p < 0.01 and severe non-hematologic toxicity was 2.8% (95% CI 1.1% – 4.8%; I2 = 0%; τ2 = 0.0; p = 0.67). The pooled prevalence of CDK4/6i dose reduction was 24.0% (95% CI 11.1% – 39.4%; I2 = 90%; τ2 = 0.052; p < 0.01) with no difference between CDK4/6i plus RT vs. CDK4/6i (odds ratio of 0.934; 95% CI 0.66 – 1.33; I2 = 0%; τ2 = 0.0; p = 0.56). The pooled prevalence of CDK4/6i discontinuation due to toxicity was 2.3% (95% CI 0.4% – 5.2%; I2 = 23%; τ2 = 0.002; p = 0.24).ConclusionThe findings of this study suggest that radiotherapy in addition to CDK4/6i treatment in breast cancer patients is generally safe and well tolerated and remains a viable treatment option.