Efficacy and Safety of Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Breast Cancer: A Systematic Review and
Hui-Chen Su1, Ho-Wei Lin2, Ka-Wai Tam3,4,5
1Department of Pharmacy, Chi Mei Medical Center, Tainan City, Taiwan.
Background:
The efficacy and safety of cyclin-dependent kinase (CDK)4/6 inhibitors in patients with breast cancer have been investigated by large-scale trials sponsored by drug companies. A lack of real-world evidence may lead to biases.
Objective:
We systematically reviewed the large-scale clinical trials and real-world data to investigate the efficacy and safety of CDK4/6 inhibitors in patients with breast cancer.
Patients And Methods:
We searched PubMed, Embase, and Cochrane Library from the inception of each database to January 2024. We included both prospective and retrospective studies reporting the survival outcomes or adverse effects of CDK4/6 inhibitors in patients with breast cancer.
Results:
We included 41 prospective trials and 80 retrospective studies involving a total of 69,535 patients. Our meta-analysis of double-arm studies revealed that all types of CDK4/6 inhibitors significantly improved overall survival and progression-free survival. The pooled estimates of the 1-year overall survival (OS) rates and 1-year progression-free survival (PFS) rates in single-arm real-world studies were 74.8% and 49.4% for abemaciclib, 84.1% and 55.7% for palbociclib, and 93.4% and 62.2% for ribobiclib, respectively. In terms of adverse effects, Asian patients were significantly more likely to experience neutropenia and increased alanine aminotransferase, whereas Western patients were significantly more likely to have grade 3 or 4 adverse effects and constipation.
Conclusions:
CDK4/6 inhibitors can improve OS and PFS in patients with advanced breast cancer. The incidence of adverse effects may differ with drugs and with ethnicity. On the basis of our findings, clinicians can select suitable CDK4/6 inhibitors for patients by conducting thorough clinical evaluations.
Insights
Cyclin-dependent kinase (CDK)4/6 inhibitors significantly improve overall survival and progression-free survival in breast cancer patients. Real-world data show varying efficacy and side effects based on drug type and patient ethnicity.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Large-scale trials investigated cyclin-dependent kinase (CDK)4/6 inhibitors for breast cancer, but real-world evidence is limited.
- Potential biases may arise from the lack of comprehensive real-world data on CDK4/6 inhibitor efficacy and safety.
Purpose of the Study:
- To systematically review large-scale clinical trials and real-world data on CDK4/6 inhibitors in breast cancer.
- To investigate the efficacy and safety profiles of CDK4/6 inhibitors across diverse patient populations.
Main Methods:
- Systematic literature search of PubMed, Embase, and Cochrane Library up to January 2024.
- Inclusion of prospective and retrospective studies reporting survival outcomes and adverse effects.
- Meta-analysis of 41 prospective trials and 80 retrospective studies involving 69,535 patients.
Main Results:
- All CDK4/6 inhibitors demonstrated significant improvements in overall survival (OS) and progression-free survival (PFS).
- Real-world 1-year OS and PFS rates varied by drug: abemaciclib (74.8%, 49.4%), palbociclib (84.1%, 55.7%), and ribociclib (93.4%, 62.2%).
- Ethnic differences in adverse effects were observed: Asian patients had higher rates of neutropenia and elevated alanine aminotransferase, while Western patients experienced more grade 3/4 adverse effects and constipation.
Conclusions:
- CDK4/6 inhibitors are effective in improving OS and PFS for advanced breast cancer.
- Adverse effect incidence varies by drug and patient ethnicity, necessitating personalized treatment selection.
- Clinicians should consider these factors for optimal CDK4/6 inhibitor selection through thorough clinical evaluation.
Related Concept Videos
02:34Inhibition of Cdk Activity
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:38Mitogens and the Cell Cycle
01:15Drugs that Stabilize Microtubules
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...