Evaluation of potential complication of interstitial lung disease with abemaciclib and palbociclib treatments

Cancer Rep (Hoboken). 2022 Jan;5(1):e1402. doi: 10.1002/cnr2.1402. Epub 2021 May 3.


Background: Various cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have demonstrated promising anti-tumor effects. The Japanese Ministry of Health, Labour and Welfare has issued a warning about interstitial lung diseases as an adverse effect of CDK4/6 inhibitors. However, a large-scale evaluation of potential complications has not been conducted to date, and the occurrence of these adverse effects is unclear.

Aim: The aim of this study was to evaluate the clinical incidence of interstitial lung disease caused by two CDK4/6 inhibitors, abemaciclib and palbociclib, and assess the relationship between each drug and interstitial lung disease.

Methods and results: We evaluated the relationship between the CDK4/6 inhibitors (abemaciclib and palbociclib) and interstitial lung disease in clinical practice using data from the Japanese Adverse Drug Event Report (JADER) database and FDA Adverse Event Reporting System (FAERS) to detect adverse event signals with reported odds ratios (RORs). Furthermore, we performed an adverse event-time analysis for each drug using data from the JADER database to examine the time of onset of the adverse events. The analysis of the reports in the JADER database showed that the lower limit of the 95% confidence interval (CI) of ROR for abemaciclib was >1 regardless of age, and a signal was detected. Interstitial lung disease associated with abemaciclib and palbociclib use has been reported, with an average onset period from treatment initiation [median (25th-75th quartile)] of 65.1 [56.0 days (25.3-98.3 days)] and 53.1 days [38.0 days (10.8-76.0 days)], respectively. The analysis of the reports in the FAERS showed that the lower limit of the 95% CI of the ROR for the two drugs was >1, and a signal was detected.

Conclusion: Treatment with abemaciclib and palbociclib is associated with a potential complication of interstitial lung disease, regardless of age.

Keywords: cyclin-dependent kinase; database; interstitial lung disease.

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Aged
  • Aminopyridines / administration & dosage
  • Aminopyridines / adverse effects*
  • Benzimidazoles / administration & dosage
  • Benzimidazoles / adverse effects*
  • Databases, Factual
  • Female
  • Humans
  • Incidence
  • Japan
  • Lung Diseases, Interstitial / chemically induced*
  • Lung Diseases, Interstitial / epidemiology
  • Male
  • Middle Aged
  • Piperazines / administration & dosage
  • Piperazines / adverse effects*
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects*
  • Pyridines / administration & dosage
  • Pyridines / adverse effects*
  • Retrospective Studies


  • Aminopyridines
  • Benzimidazoles
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyridines
  • abemaciclib
  • palbociclib