Progress in Clinical Trials of CDK4/6 Inhibitors

Abstract Purpose of Review To discuss the biological mechanisms of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, the rationale for using CDK4/6 inhibitors in estrogen receptor-positive (ER+) and human epidermal growth factor receptor-2-negative (HER2-) breast cancer (BC), data from landmark phase III clinical trials that led to U.S. Food and Drug Administration (FDA) approval, and updates on recently published and ongoing clinical trials. Finally, we explore future directions of CDK4/6 inhibitors in the management of ER+ and HER2- BC. Recent Findings Based on landmark phase III clinical trials, CDK4/6 inhibitors have become essential to treat ER+ and HER2- BC. Summary New therapeutic strategies focused on CDK4/6 inhibitors are being evaluated and are expected to enter future pre-clinical and clinical trials, expanding the use of CDK4/6 inhibitors beyond currently FDA-approved indications.