Pharmacokinetic drug evaluation of ribociclib for the treatment of metastatic, hormone-positive breast cancer

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Introduction: Cyclin D-cyclin-dependent kinase (CDK) 4/6-inhibitor of CDK4/6-retinoblastoma (Rb) pathway hyperactivation is associated with hormone receptor-positive (HR+) breast cancer (BC). Ribociclib is an orally bioavailable, highly selective small molecule inhibitor of CDK4/6 that induces G1 arrest at sub-micromolar concentrations in a variety of pRb-positive cancer cells in vitro. Ribociclib is a new standard of care for metastatic HR+/HER2 negative metastatic breast cancer. Area covered: In this article, we review the preclinical and clinical development of ribociclib as well as discussing the role for novel applications of these agents outside the arena of HR-positive, HER2-negative advanced breast cancer. Expert opinion: Results of pivotal phase II and III trials investigating ribociclib in patients with advanced-stage (HR)-positive breast cancer have demonstrated a substantial improvement in progression-free survival, with a safe toxicity profile. Mechanisms of acquired resistance to CDK4/6 inhibitors are beginning to emerge and might enable rational post-CDK4/6 inhibitor therapeutic strategies to be identified. Extending the use of CDK4/6 inhibitors beyond ER-positive breast cancer is challenging, and will likely require biomarkers that are predictive of a response. The use of combination therapies to optimize CDK4/6 targeting is under development.

Original languageEnglish
Pages (from-to)575-581
Number of pages7
JournalExpert Opinion on Drug Metabolism and Toxicology
Issue number5
Publication statusPublished - May 4 2017


  • CDK 4/6 pathway
  • hormone receptor positive
  • metastatic breast cancer
  • pharmacodynamics
  • pharmacokinetics
  • ribociclib

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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