Use of cyclin-dependent kinase (CDK) 4/6 inhibitors for hormone receptor-positive, human epidermal growth factor receptor 2-negative, metastatic breast cancer: a roundtable discussion by The Breast Cancer Therapy Expert Group (BCTEG)

Abstract

Thus far, three CDK 4/6 inhibitors-palbociclib, ribociclib, and more recently, abemaciclib-have been approved for use in the setting of HR+, HER2-, mBC. The degrees to which these agents differ in terms of CDK4/6 affinity, side-effect profiles, dosing, degree of central nervous system (CNS) penetration, optimal use in combination with antiestrogen therapy, and across other subsets of breast cancer, remain an active area of investigation.

Case-Based Review and Clinical Guidance on the Use of Genomic Assays for Early-Stage Breast Cancer: Breast Cancer Therapy Expert Group (BCTEG)

“…In previous meetings, the group has addressed issues related to ET in early-stage breast cancer, the use of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in patients with metastatic breast cancer, and the treatment of HER2 À positive breast cancer. [1][2][3] In January 2019, the group convened to discuss issues surrounding the use of genomic testing as a means to guide treatment decisions in EBC. An unrestricted educational grant for this activity was provided by Agendia Inc, Bio-Theranostics Inc, Myriad Inc, and Nanostring Inc.…”

The CDK 4/6 inhibitor ribociclib has activity in the treatment of inoperable desmoid tumor. A case report

“…Ribociclib is a highly specific cdk 4/6 inhibitor that binds to the complex of cyclin D1 and cdk 4 or 6 and thereby induces cell cycle arrest. Cdk 4/6 inhibitors have exhibited high efficacy in advanced ER positive breast cancer by substantial PFS prolongation [5,21]. In DTs, b-catenin accumulation has been associated with cyclin D1 overexpression [22].…”

“…Cyclin D1 expression has varied in different series from 44% to 71% [22][23][24]. In breast cancer, cdk 4/6 inhibitors act synergistically with antiestrogen treatment [5]. Moreover, several lines of evidence indicate estrogen dependence of DTs.…”

“…Uncontrolled proliferation leads to tumorigenesis. Palbociclib, ribociclib, and abemaciclib are European Medicines Agency and U.S. Food and Drug Administration approved cdk 4/6 inhibitors for advanced breast cancer used in combination with hormonal therapy [5]. In phase-II study of palbociclib in well differentiated or dedifferentiated liposarcoma, the median progression free survival (PFS) was 17.9 weeks with one complete response noted [6].…”

A paradigm shift for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer: a review of CDK inhibitors

“…For many decades, blockade of estrogen receptor signaling was the basis for local, advanced, and metastatic HR+/HER2− breast cancer treatment; however, all advanced breast cancer patients eventually developed resistance to endocrine therapy (ET) throughout the course of their disease. 5 …”