Related Experiment Video
Updated: Oct 16, 2025
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
A deep dive into CDK4/6 inhibitors: Evaluating real world toxicities and treatment paradigms in the elderly
Coral Olazagasti1, Chung-Shien Lee1,2, Angel Liu2
1Division of Medical Oncology and Hematology, Donald and Barbara Zucker School of Medicine at Hofstra/5799Northwell Health, New Hyde Park, New York, USA.
Background:
Cyclin-dependent kinase 4/6 inhibitors have become part of the standard of care in the treatment of hormone receptor positive, Her2Neu negative metastatic breast cancer. There is concern regarding the efficacy and potential increased cyclin-dependent kinase 4/6 inhibitors toxicity in the geriatric population in the community compared to the clinical trial population.
Methods:
We evaluated patients treated with cyclin-dependent kinase 4/6 inhibitors from 2015 to 2019 and stratified according to age ≥70 and <70 years. Complete blood count from the first two cycles was recorded. Rates of hematologic toxicities, dose interruptions and reductions, progression-free survival, and overall survival were compared between both groups. We sought to assess the hematologic toxicities between the age groups and the relationship between previous chemotherapy exposure, bone metastasis and starting cyclin-dependent kinase 4/6 inhibitors dose with progression-free survival and overall survival.
Results:
A total of 202 patients were included, 73 were ≥70 years and 129 were <70 years of age. There was no association between age group and grade of neutropenia or thrombocytopenia. There was a profound association between progression-free survival and overall survival and starting dose, where patients with recommended starting dose had higher progression-free survival and overall survival than those with a reduced dose (p = 0.0003 and p = 0.04).
Conclusions:
Our study showed similar progression-free survival and overall survival between age groups without significant differences in neutropenia or thrombocytopenia toxicity. Nevertheless, we found an association between starting dose and progression-free survival and overall survival that has not been previously reported. Given the good tolerability across age groups and the improvement in progression-free survival and overall survival, patients should be treated at the cyclin-dependent kinase 4/6 inhibitors recommended dose and monitored appropriately.
Insights
Cyclin-dependent kinase 4/6 inhibitors show similar efficacy and toxicity in older adults compared to younger patients. Treatment at the recommended dose, not age, significantly impacts progression-free and overall survival in metastatic breast cancer.
Area of Science:
- Oncology
- Pharmacology
Background:
- Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are standard treatment for HR+, HER2- metastatic breast cancer.
- Concerns exist regarding CDK4/6 inhibitor efficacy and toxicity in geriatric patients compared to clinical trial populations.
Purpose of the Study:
- To compare the efficacy and toxicity of CDK4/6 inhibitors in patients aged ≥70 versus <70 years.
- To assess the relationship between prior chemotherapy, bone metastasis, and starting CDK4/6 inhibitor dose with survival outcomes.
Main Methods:
- Retrospective evaluation of 202 patients treated with CDK4/6 inhibitors (2015-2019).
- Stratification by age (≥70 vs. <70 years).
- Comparison of hematologic toxicities, dose modifications, progression-free survival (PFS), and overall survival (OS).
Main Results:
- No significant difference in neutropenia or thrombocytopenia between age groups.
- Starting dose was strongly associated with PFS and OS (p=0.0003 and p=0.04).
- Patients receiving the recommended starting dose had superior PFS and OS.
Conclusions:
- CDK4/6 inhibitors demonstrate comparable PFS and OS between geriatric and younger adult patients.
- Hematologic toxicity (neutropenia, thrombocytopenia) was similar across age groups.
- Recommended CDK4/6 inhibitor dosing is crucial for optimizing PFS and OS, irrespective of age.
Related Concept Videos
01:15Drug Dosing: Geriatric Patients
01:18Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Excretion
01:18Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Metabolism
01:27Pharmacodynamics in Geriatric Patients: Effects of Age
02:34Inhibition of Cdk Activity
01:00Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Distribution