Introduction: Breast cancer remains a major cause of morbidity and mortality worldwide. Given the central role of cyclin-dependent kinases in regulating cell division, there has been a longstanding interest in developing compounds which target the cyclin D1: CDK4/6 axis in breast cancer. The recent discovery of potent and selective CDK4/6 inhibitors (CDK4/6i) was an important breakthrough.
Areas covered: There are three CDK4/6i in clinical development (palbociclib, ribociclib and abemaciclib). Phase II and III studies using palbociclib in combination with endocrine therapy demonstrated remarkable clinical activity in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer, resulting in two separate FDA approvals in 2015 and 2016. In this article, we review the preclinical and clinical development of these compounds 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: In combination with endocrine therapy, CDK4/6i have shown promising efficacy in patients with advanced HR-positive, HER2-negative advanced breast cancer. Numerous trials in a variety of clinical settings and in different tumor types are ongoing or planned.
Keywords: Abemaciclib; CDK4/6 inhibitors; endocrine resistance; palbociclib; ribociclib.