Incidence of and risk factors for non-hematologic toxicity with combined radiotherapy and CDK4/6 inhibitors in metastatic breast cancer using dose-volume parameters analysis: a multicenter cohort study

Breast Cancer. 2023 Mar;30(2):282-292. doi: 10.1007/s12282-022-01422-5. Epub 2022 Dec 17.

Abstract

Background: There is a lack of data on combined radiotherapy (RT) and cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) risk factors and toxicity. This study aimed to assess the incidence of and risk factors for non-hematologic toxicities in patients treated with combined RT and CDK4/6i using dose-volume parameter analysis.

Methods: We conducted a retrospective multicenter cohort study of patients with metastatic breast cancer receiving RT within 14 days of CDK4/6i use. The endpoint was non-hematologic toxicities. Patient characteristics and RT treatment planning data were compared between the moderate or higher toxicities (≥ grade 2) group and the non-moderate toxicities group.

Results: Sixty patients were included in the study. CDK4/6i was provided at a median daily dose of 125 mg and 200 mg for palbociclib and abemaciclib, respectively. In patients who received concurrent RT and CDK4/6i (N = 29), the median concurrent prescribed duration of CDK4/6i was 14 days. The median delivered RT dose was 30 Gy and 10 fractions. The rate of grade 2 and 3 non-hematologic toxicities was 30% and 2%, respectively. There was no difference in toxicity between concurrent and sequential use of CDK4/6i. The moderate pneumonitis group had a larger lung V20 equivalent dose of 2 Gy per fraction and planning target volume than the non-moderate pneumonitis group.

Conclusions: Moderate toxicities are frequent with combined RT and CDK4/6i. Caution is necessary concerning the combined RT and CDK4/6i. Particularly, reducing the dose to normal organs is necessary for combined RT and CDK4/6i.

Keywords: Adverse events; Combined modality therapy; Palliation; Radiation therapy; Safety.

Publication types

  • Multicenter Study

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Breast Neoplasms* / pathology
  • Cohort Studies
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6
  • Cyclin-Dependent Kinase Inhibitor p18 / therapeutic use
  • Female
  • Humans
  • Incidence
  • Protein Kinase Inhibitors / therapeutic use

Substances

  • Cyclin-Dependent Kinase Inhibitor p18
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6
  • Protein Kinase Inhibitors
  • CDK4 protein, human