HR+, HER2– Advanced Breast Cancer and CDK4/6 Inhibitors: Mode of Action, Clinical Activity, and Safety Profiles
[ Vol. 17 , Issue. 7 ]
Sarah L. Sammons, Donna L. Topping and Kimberly L. Blackwell*Pages 637-649 (13)
Background: Cyclin-dependent kinase (CDK) 4/6 inhibitor-based therapies have shown great promise in improving clinical outcomes for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer.
Objectives: 1. Discuss the mode of action of the three CDK4/6 inhibitors in late clinical development: palbociclib (PD-0332991; Pfizer), ribociclib (LEE011; Novartis), and abemaciclib (LY2835219; Lilly). 2. Describe the efficacy and safety data relating to their use in HR+, HER2– advanced breast cancer. 3. Discuss the key side effects associated with CDK4/6 inhibitors along with considerations for adverse event management and patient monitoring.
Method: Relevant information and data were assimilated from manuscripts, congress publications, and online sources.
Results: CDK4/6 inhibitors have demonstrated improved progression-free survival in combination with endocrine therapy compared with endocrine therapy alone. The side-effect profile of each agent is described, along with implications for patient monitoring, and considerations for patient care providers and pharmacists.
Conclusion: Addition of a CDK4/6 inhibitor to endocrine therapy increases efficacy and delays disease progression. Insight into the unique side-effect profiles of this class of agents and effective patient monitoring will facilitate the successful use of CDK4/6 inhibitor-based therapies in the clinic.
Abemaciclib, advanced breast cancer, CDK4/6 inhibitor, hormone receptor-positive, palbociclib, ribociclib.
Department of Medicine, Duke University Medical Center, Duke University, Durham, NC, Department of Medicine, Duke University Medical Center, Duke University, Durham, NC, Duke University Medical Center, 10 Bryan Searle Drive, Suite 456B, Seeley G. Mudd Building, Durham, NC 27710
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