Safety and Treatment Continuity of Switching between CDK4/6 Inhibitors for Metastatic Breast Cancer due to Adverse Events: An Exploratory Single-Center Study in Japan

Oncology. 2026;104(6):628-638. doi: 10.1159/000548801. Epub 2025 Oct 3.

Abstract

Introduction: Palbociclib and abemaciclib, CDK4/6 inhibitors with a shared primary mechanism of action, differ in their adverse effect profiles. We encountered several cases of switching between CDK4/6 inhibitors following treatment discontinuation owing to adverse events (AEs) in clinical practice.

Methods: In this study, we evaluated the safety and treatment continuity of switching between palbociclib and abemaciclib for hormone receptor-positive HER2-negative metastatic or recurrent breast cancer (HR+/HER2-MBC) in patients and prescribed these agents between January 1, 2018, and August 31, 2024, at Ogaki Municipal Hospital. Patients who did not discontinue treatment owing to AEs were defined as the non-AE group (79 patients), those who switched to another CDK4/6 inhibitor after treatment discontinuation owing to AEs were defined as the AE-switch group (16 patients), and those who did not switch to another CDK4/6 inhibitor after treatment discontinuation owing to AEs were defined as the AE-stop group (13 patients).

Results: The main AEs for which treatment was discontinued included neutropenia, interstitial lung disease, increased AST and ALT levels, gastrointestinal symptoms, and skin disorders. Switching only caused recurrent neutropenia, with no serious recurrence being observed for the other AEs. The median progression-free survival in the non-AE, AE-switch, and AE-stop groups was 392, 1,043, and 203 days (p = 0.00858), and the median overall survival was 1,598, 3,725, and 1,701 days (p = 0.269), respectively.

Conclusion: These results suggest that switching following the emergence of AEs may be useful in terms of safety and treatment continuity of CDK4/6 inhibitor therapy for HR+/HER2-MBC. However, since this study was an exploratory analysis based on real-world data from a single center in Japan, further validation through large-scale, prospective, multicenter clinical trials is warranted.

Keywords: CDK4/6 inhibitors; Metastatic breast cancer; Safety; Switching due to adverse events; Treatment continuity.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aminopyridines* / administration & dosage
  • Aminopyridines* / adverse effects
  • Benzimidazoles* / administration & dosage
  • Benzimidazoles* / adverse effects
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / pathology
  • Cyclin-Dependent Kinase 4* / antagonists & inhibitors
  • Cyclin-Dependent Kinase 6* / antagonists & inhibitors
  • Drug Substitution*
  • Erb-b2 Receptor Tyrosine Kinases / metabolism
  • Female
  • Humans
  • Japan
  • Middle Aged
  • Neoplasm Metastasis
  • Piperazines* / administration & dosage
  • Piperazines* / adverse effects
  • Protein Kinase Inhibitors* / administration & dosage
  • Protein Kinase Inhibitors* / adverse effects
  • Protein Kinase Inhibitors* / therapeutic use
  • Pyridines* / administration & dosage
  • Pyridines* / adverse effects

Substances

  • Cyclin-Dependent Kinase 6
  • Cyclin-Dependent Kinase 4
  • Protein Kinase Inhibitors
  • Pyridines
  • palbociclib
  • Piperazines
  • Benzimidazoles
  • abemaciclib
  • Aminopyridines
  • CDK6 protein, human
  • CDK4 protein, human
  • Erb-b2 Receptor Tyrosine Kinases