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

Marcin Kubeczko; Michał Jarząb; Dorota Gabryś; Aleksandra Krzywon; Alexander J Cortez; Amy J Xu

doi:10.1016/j.radonc.2023.109839

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

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

Authors

Marcin Kubeczko¹, Michał Jarząb², Dorota Gabryś³, Aleksandra Krzywon⁴, Alexander J Cortez⁴, Amy J Xu⁵

Affiliations

¹ Breast Cancer Center, Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Poland. Electronic address: marcin.kubeczko@io.gliwice.pl.
² Breast Cancer Center, Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Poland.
³ Department of Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Poland.
⁴ Department of Biostatistics and Bioinformatics, Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Poland.
⁵ Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York City, USA.

PMID: 37536378
DOI: 10.1016/j.radonc.2023.109839

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%; 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).

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.

Keywords: CDK 4/6 inhibitors; Radiotherapy; Toxicity.

Publication types

Meta-Analysis
Systematic Review
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Combined Chemotherapy Protocols
Breast Neoplasms* / drug therapy
Breast Neoplasms* / radiotherapy
Consensus
Cyclin-Dependent Kinase 4
Epidermal Growth Factor
Feasibility Studies
Female
Humans
Middle Aged
Protein Kinase Inhibitors / adverse effects
Radiotherapy

Substances

CDK4 protein, human
Cyclin-Dependent Kinase 4
Epidermal Growth Factor
Protein Kinase Inhibitors