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Expert Opin Drug Metab Toxicol. 2017 May;13(5):575-581. doi: 10.1080/17425255.2017.1318848. Epub 2017 Apr 21.

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

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a Early Drugs Development for Innovative Therapies Division , European Institute of Oncology , Milan , Italy.
b Division of Senology , European Institute of Oncology , Milan , Italy.
c School of Medicine , University of Milano , Milan , Italy.


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.


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

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