CDK 4/6 Inhibitors in Breast Cancer: Current Controversies and Future Directions

Curr Oncol Rep. 2019 Feb 26;21(3):25. doi: 10.1007/s11912-019-0769-3.

Abstract

Purpose of review: To describe the clinical role of CDK 4/6 inhibitors in hormone receptor-positive (HR+) metastatic breast cancer (HR+ MBC) as well as current controversies and evolving areas of research.

Recent findings: Palbociclib, ribociclib, and abemaciclib are each approved in combination with an aromatase inhibitor or fulvestrant for HR+ MBC. Abemaciclib is also approved as monotherapy for pre-treated patients. Key questions in the field include whether all patients with HR+ MBC should receive a CDK 4/6 inhibitor up front versus later line, impact on overall survival, role of continued CDK 4/6 blockade, mechanism of clinical resistance, and treatment sequencing. The development of CDK 4/6 inhibitors has changed the therapeutic management of HR+ MBC. Additional research is needed to determine optimal treatment sequencing, understand mechanisms governing resistance, and develop novel therapeutic strategies to circumvent or overcome clinical resistance and further improve the outcomes of patients with MBC.

Keywords: Abemaciclib; Clinical trials; Cyclin-dependent kinases 4 and 6; Metastatic breast cancer; Palbociclib; Resistance mechanisms; Ribociclib.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / pathology
  • Cyclin-Dependent Kinase 4 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase 6 / antagonists & inhibitors*
  • Drug Resistance, Neoplasm*
  • Female
  • Humans
  • Protein Kinase Inhibitors / therapeutic use*

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • CDK4 protein, human
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6