Optimal Use of CDK4/6 Inhibitors in Breast Cancer

Virginia Kaklamani, MD; Harold J. Burstein, MD, PhD


April 18, 2023

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have become integral to the treatment of HR+/HER2- breast cancer. Approved in 2015 for use in the metastatic setting and most recently in the adjuvant setting, CDK4/6 inhibitors have revolutionized treatment in both endocrine-sensitive and endocrine-resistant settings and in pre- and postmenopausal women.

But many questions remain regarding the optimal use of these medications in clinical practice.

In this ReCAP, Dr Virginia Kaklamani from the University of Texas Health Sciences Center in San Antonio, Texas, and Dr Harold Burstein from Dana-Farber Cancer Institute, Boston, Massachusetts, begin their discussion by examining the potential role of adjuvant CDK4/6 inhibitor therapy in early, high-risk breast cancer.

They discuss the three main studies that looked at the role of adjuvant CDK4/6 inhibitors, including the PALLAS and PENELOPE-B trials, in which palbociclib showed no benefit in invasive disease-free survival. In contrast, in the monarchE trial, abemaciclib showed a robust benefit in preventing recurrence, which was sustained after longer follow-up, as reported at the San Antonio Breast Cancer Symposium 2022.

Turning to the metastatic setting, the panelists discuss the varied side effect profiles of the three approved CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib. They also discuss current research into the continuation of these agents beyond progression and whether sequencing of CDK4/6 inhibitors may provide benefit.


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