Pharmacokinetic drug evaluation of ribociclib for the treatment of metastatic, hormone-positive breast cancer. (4th May 2017)

• Record Type: Journal Article
• Authors: Curigliano, Giuseppe; Criscitiello, Carmen; Esposito, Angela; Intra, Mattia; Minucci, Saverio
• Is Part Of: Expert opinion on drug metabolism and toxicology. Volume 13:Number 5(2017:May)
• Page Start: 575
• Page End: 581
• Publication Date: 2017-05-04
• Subjects: CDK 4/6 pathway -- hormone receptor positive -- metastatic breast cancer -- pharmacokinetics -- pharmacodynamics -- ribociclib; Drugs -- Toxicology -- Periodicals; Drugs -- Metabolism -- Periodicals; 615.7
• DOI: 10.1080/17425255.2017.1318848
• Languages: English
• ISSNs: 1742-5255

Abstract

ABSTRACT: 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.