Related Experiment Video
Updated: Feb 7, 2026
Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
Published on: May 3, 2018
Review of Cyclin-Dependent Kinase 4/6 Inhibitors for the Treatment of Hormone Receptor-Positive Advanced Breast
Keith A Hecht1, Christopher Selby2
11 Southern Illinois University Edwardsville School of Pharmacy, IL, USA.
Objective:
To evaluate the existing literature regarding the use of cyclin-dependent kinase (CDK) 4/6 inhibitors in the treatment of hormone receptor-positive advanced breast cancer (ABC).
Data Sources:
A search of the medical literature was performed using PubMed (2014 to June 2018). Search terms included cyclin-dependent kinase, CDK, breast cancer, palbociclib, ribociclib, abemaciclib, PD0332991, LEE011, and LY2835219. Clinicaltrials.gov was also searched.
Study Selection And Data Extraction:
Trials with clinical efficacy outcomes evaluating CDK 4/6 inhibitors in the treatment of advanced hormone-positive breast cancer were considered.
Data Synthesis:
Palbociclib, abemaciclib, and ribociclib each demonstrated significant benefit when combined with an aromatase inhibitor, the benefit to patients was similar for each, with an improvement of 42% to 51% in median progression-free survival (PFS). In combination with fulvestrant, CDK 4/6 inhibitors used for the treatment of hormone receptor-positive ABC resulted in a 43% to 58% improvement in median PFS versus fulvestrant alone. CDK inhibitors are relatively well tolerated; however, discontinuation as a result of adverse effects was highest with abemaciclib. Relevance to Patient Care and Clinical Practice: This review considers the use of the 3 commercially available CDK 4/6 inhibitors for treatment of hormone receptor-positive breast cancer, including data on each of the 3 agents in newly advanced and treatment refractory disease.
Conclusions:
The CDK inhibitors should be used in combination with endocrine therapies for the treatment of ABC. Efficacy of the 3 agents is similar. Selection within the class should include consideration of adverse effects and drug interactions.
Insights
Cyclin-dependent kinase (CDK) 4/6 inhibitors significantly improve progression-free survival in advanced hormone receptor-positive breast cancer when combined with endocrine therapy. Efficacy is similar across agents, but adverse effects and drug interactions should guide selection.
Area of Science:
- Oncology
- Pharmacology
- Clinical Medicine
Background:
- Hormone receptor-positive advanced breast cancer (HR+ ABC) remains a significant clinical challenge.
- Cyclin-dependent kinase (CDK) 4/6 inhibitors represent a novel therapeutic class for HR+ ABC.
- Evaluating the efficacy and safety of available CDK 4/6 inhibitors is crucial for clinical decision-making.
Purpose of the Study:
- To conduct a literature review on the use of CDK 4/6 inhibitors in HR+ ABC.
- To synthesize data on the efficacy and tolerability of palbociclib, ribociclib, and abemaciclib.
- To inform clinical practice regarding the selection and use of these agents.
Main Methods:
- Systematic literature search of PubMed and ClinicalTrials.gov from 2014 to June 2018.
- Inclusion of trials reporting clinical efficacy outcomes for CDK 4/6 inhibitors in HR+ ABC.
- Data extraction focused on progression-free survival (PFS) and adverse events.
Main Results:
- CDK 4/6 inhibitors combined with aromatase inhibitors improved median PFS by 42%-51%.
- CDK 4/6 inhibitors combined with fulvestrant improved median PFS by 43%-58% compared to fulvestrant alone.
- All three agents (palbociclib, ribociclib, abemaciclib) showed similar efficacy, with abemaciclib having the highest discontinuation rate due to adverse effects.
Conclusions:
- CDK 4/6 inhibitors are recommended in combination with endocrine therapies for HR+ ABC.
- The efficacy of the three available CDK 4/6 inhibitors is comparable.
- Patient selection should consider individual adverse effect profiles and potential drug interactions.
Related Concept Videos
01:26Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
01:45Positive Regulator Molecules
01:26Receptor Tyrosine Kinases
01:23Dipeptidyl Peptidase 4 Inhibitors
01:08Intracellular Hormone Receptors
01:25cAMP-dependent Protein Kinase Pathways