CDK4/6 抑制剂联合放疗治疗 HR 阳性/HER2 阴性乳腺癌的安全性和可行性：系统评价和荟萃分析。

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.

机构信息

Breast Cancer Center, Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Poland.

出版信息

Radiother Oncol. 2023 Oct;187:109839. doi: 10.1016/j.radonc.2023.109839. Epub 2023 Aug 1.

DOI:10.1016/j.radonc.2023.109839

PMID:37536378

Abstract

BACKGROUND AND PURPOSE

The 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 METHODS

A 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.

RESULTS

Fifteen 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%; I = 93%; τ = 0.084; p < 0.01 and severe non-hematologic toxicity was 2.8% (95% CI 1.1% - 4.8%; I = 0%; τ = 0.0; p = 0.67). The pooled prevalence of CDK4/6i dose reduction was 24.0% (95% CI 11.1% - 39.4%; I = 90%; τ = 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; I = 0%; τ = 0.0; p = 0.56). The pooled prevalence of CDK4/6i discontinuation due to toxicity was 2.3% (95% CI 0.4% - 5.2%; I = 23%; τ = 0.002; p = 0.24).

CONCLUSION

The 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.

摘要

背景与目的

细胞周期蛋白依赖性激酶 4/6 抑制剂（CDK4/6i）联合内分泌治疗激素受体阳性（HR+）人表皮生长因子 2 阴性（HER2-）乳腺癌，显著改善了总生存期，改变了临床实践。然而，关于 CDK4/6i 联合放疗的安全性存在相互矛盾的数据，目前尚无共识指南来指导临床实践。本研究进行了一项荟萃分析，以评估 CDK4/6i 联合放疗的安全性和可行性。

材料与方法

通过在 PubMed/MEDLINE、Web of Science 和 Scopus 中进行全面检索，评估 HR+/HER2-乳腺癌患者接受 CDK4/6i 联合放疗时的安全性（3-5 级不良事件）、CDK4/6i 剂量减少和因毒性而停药的发生率。

结果

共纳入 15 项研究，包括 1133 例 HR+/HER2-乳腺癌患者。其中 617 例患者接受 CDK4/6i 联合放疗；中位随访时间为 17.0 个月（IQR 9.2-18.0），中位年龄为 58.8 岁（IQR 55.5-62.5）。严重血液学毒性的总发生率为 29.4%（95%CI 14.0%-47.4%；I=93%；τ=0.084；p<0.01），严重非血液学毒性的总发生率为 2.8%（95%CI 1.1%-4.8%；I=0%；τ=0.0；p=0.67）。CDK4/6i 剂量减少的总发生率为 24.0%（95%CI 11.1%-39.4%；I=90%；τ=0.052；p<0.01），与 CDK4/6i 联合放疗组相比，CDK4/6i 单药组的差异无统计学意义（比值比为 0.934；95%CI 0.66-1.33；I=0%；τ=0.0；p=0.56）。因毒性而停止 CDK4/6i 治疗的总发生率为 2.3%（95%CI 0.4%-5.2%；I=23%；τ=0.002；p=0.24）。