A narrative review of the clinical development of CDK4/6 inhibitor abemaciclib in breast cancer

Abstract

Background and Objective: Advanced or metastatic breast cancer (MBC) is associated with poor prognosis and presents many challenges in medical management and treatment decisions. Anticancer drugs that act on cell cycle mechanisms have shown great potential in preclinical studies. In clinical trials, abemaciclib, a reversible ATP-competitive cyclin-dependent kinase 4/6 (CDK4/6) inhibitor developed by Eli Lilly and Company, combined with endocrine therapy (ET) were associated with superior outcomes compared with ET alone in patients with advanced or metastatic hormone receptor positive (HR + )/human epidermal growth factor receptor 2 negative (HER2 − ) breast cancer, representing a new standard-of-care in this population. Abemaciclib has been approved by the U.S. Food and Drug Administration (FDA) for use in HR + /HER2 − MBC. In China, abemaciclib was also approved by the National Medical Products Administration (NMPA) based on findings from the MONARCH plus trial. Recently, abemaciclib have been approved as the first and only CDK4/6 inhibitor by FDA and NMPA for use in HR + /HER2 − , node-positive, early breast cancer (EBC) at high risk of recurrence and Ki-67 score ≥20%. Further trials of abemaciclib are ongoing. This is an overview of the clinical development of abemaciclib in breast cancer. Methods: We reviewed English publications in PubMed related to CDK4/6 inhibitors from 2011 to 2021.

An Overview of the Safety Profile and Clinical Impact of CDK4/6 Inhibitors in Breast Cancer—A Systematic Review of Randomized Phase II and III Clinical Trials

“…It will be crucial to ascertain whether more CDK4/6 inhibitors might be used in future therapies. Future research and development should focus on selecting the right pharmaceuticals for use in conjunction with CDK4/6 inhibitors, as a number of novel medications are being tested in the clinic [ 51 ].…”

“…However, ongoing suppression of CDK4/6 will result in apoptosis and a persistent arrest of the cell cycle. In the cerebrospinal fluid and plasma, abemaciclib has similar drug concentrations and can also penetrate the blood–brain barrier [ 51 ]. Therefore, an important subject being investigated in clinical studies is whether abemaciclib may be useful in treating patients with brain metastases or in lowering the risk of getting brain metastases.…”

“…Furthermore, it is not known whether abemaciclib’s biological capacity to penetrate the blood–brain barrier will one day make it a viable therapy choice for individuals with brain metastases due to breast cancer [ 51 ].…”

“…In clinical studies, an increase in serum creatinine was observed during the first 28-day cycle of abemaciclib administration. Serum creatinine remained elevated but remained stable during treatment and was reversible when treatment was discontinued [ 51 ].…”