Safety of cyclin-dependent kinase4/6 inhibitor combined with palliative radiotherapy in patients with metastatic breast cancer

Breast. 2021 Dec:60:163-167. doi: 10.1016/j.breast.2021.10.001. Epub 2021 Oct 9.

Abstract

Introduction: Cyclin-dependent kinase (CDK)4/6 inhibitor is a first-line therapy for metastatic ER+/HER2-breast cancer. However, there are limited data on safety of combined radiotherapy (RT) and CDK4/6 inhibition.

Methods: We conducted a retrospective study of women with metastatic breast cancer who received palliative RT within 14 days of CDK4/6 inhibitor use. The primary endpoint was toxicity per Common Terminology Criteria for Adverse Events v5. Secondary endpoints were pain response and local control based on clinical assessment and imaging.

Results: Thirty patients underwent 36 RT courses with palbociclib (n = 34 courses, 94.4%) or abemaciclib (n = 2, 5.6%). RT was delivered before, concurrently or after CDK4/6 inhibitors in 7 (19.4%), 8 (22.2%), and 21 (58.3%) of cases with median 3.5 days from RT to closest CDK4/6 inhibitor administration. Median RT dose was 30Gy (range 8-40.05Gy). Treated sites included brain (n = 5, 11.6%), spine (n = 19, 44.2%), pelvis (n = 9, 20.9%), other bony sites (n = 6, 14.0%) and others (n = 4, 9.3%). No acute grade ≥3 non-hematologic toxicity occurred. No increased hematologic toxicity was attributable to RT with grade 3 hematologic toxicities rates 16.7%, 0%, and 6.7% before, during, and 2 weeks after RT completion. All but one patient (29/30) achieved symptom relief. Local control rates were 94.4%, 91.7% at 6 and 12 months.

Conclusions: The use of RT within 2 weeks of CDK4/6 inhibitors had low acceptable toxicity and high efficacy, suggesting that it is safe for palliation of metastatic breast cancer.

Keywords: CDK4/6 inhibitor; Metastatic breast cancer; Palliation; Radiotherapy; Safety.

MeSH terms

  • Aminopyridines / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols
  • Benzimidazoles / therapeutic use
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / radiotherapy
  • Cyclin-Dependent Kinase 4 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase 6 / antagonists & inhibitors*
  • Female
  • Humans
  • Piperazines / therapeutic use
  • Protein Kinase Inhibitors* / therapeutic use
  • Pyridines / therapeutic use
  • Retrospective Studies

Substances

  • Aminopyridines
  • Benzimidazoles
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyridines
  • abemaciclib
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6
  • palbociclib