CDK4/6 Inhibition in the Metastatic Setting: Where Are We Headed?

Curr Treat Options Oncol. 2023 Sep;24(9):1103-1119. doi: 10.1007/s11864-023-01109-9. Epub 2023 Jun 14.


Hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER-2-) metastatic breast cancer (MBC) is the most common subtype of breast cancer. Due to therapeutic advances with molecularly targeted therapies, the prognosis for patients with metastatic disease has improved significantly. The advent of CDK4/6 inhibitors (CDK4/6i) has changed the treatment paradigm for patients with HR+HER2-MBC. CDK4/6i allowed for marked improvement in overall survival, delaying the time to chemotherapy initiation, and improved quality of life for our patients. Efforts are now focused on the best approach(es) for patients after progression on CDK4/6i. Can we further harness the benefit of CDK4/6i in novel combinations at the time of progression? Should we continue CDK4/6i or proceed other novel agents or endocrine therapies? As we advance our treatment strategies for HR+HER2-MBC, there is no longer a one-size-fits-all model, but instead a multifaceted and personalized approach lending to improved outcomes for our patients.

Keywords: CDK4/6 inhibitor; Endocrine resistance, ctDNA; Hormone therapy; Metastatic breast cancer.

Publication types

  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Breast Neoplasms* / drug therapy
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6
  • Female
  • Humans
  • Molecular Targeted Therapy
  • Neoplasms, Second Primary*
  • Oncogenes
  • Quality of Life
  • Receptor, ErbB-2


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