Implementing geriatric assessment for dose optimization of CDK4/6 inhibitors in older breast cancer patients

Future Oncol. 2024;20(37):2937-2948. doi: 10.1080/14796694.2024.2413841. Epub 2024 Oct 21.

Abstract

Current evidence from both randomized trials and real-world studies suggests that older patients with advanced hormone receptor-positive/HER2-negative (HR+/HER2) breast cancer derive clinical benefit from the addition of CDK4/6 inhibitors to endocrine therapy. However, a higher risk for adverse events due to CDK4/6 inhibitors among older patients is evident, leading to a trend of initiating CDK4/6 inhibitors at lower dose in clinical practice, though without evidence. The aim of the IMPORTANT-trial, a pragmatic, multinational, open-label, partly decentralized randomized trial is to investigate whether lower starting dose of CDK4/6 inhibitors combined with endocrine therapy is comparable to full dose in older (≥70 years old) patients with advanced HR+/HER2- breast cancer who are assessed as vulnerable or frail based on comprehensive geriatric assessment.Clinical Trial Registration: NCT06044623 (ClinicalTrials.gov); Registration date: 13 September 2023.

Keywords: CDK4/6 inhibitors; advanced breast cancer; comprehensive geriatric assessment; lower dose; randomized.

Plain language summary

[Box: see text].

Publication types

  • Clinical Trial Protocol
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / pathology
  • Cyclin-Dependent Kinase 4* / antagonists & inhibitors
  • Cyclin-Dependent Kinase 6* / antagonists & inhibitors
  • Female
  • Geriatric Assessment*
  • Humans
  • Multicenter Studies as Topic
  • Protein Kinase Inhibitors* / administration & dosage
  • Protein Kinase Inhibitors* / adverse effects
  • Protein Kinase Inhibitors* / therapeutic use
  • Randomized Controlled Trials as Topic
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptor, ErbB-2 / metabolism

Substances

  • CDK4 protein, human
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6
  • Protein Kinase Inhibitors
  • Receptor, ErbB-2

Associated data

  • ClinicalTrials.gov/NCT06044623