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Meta-analysis of selected toxicity endpoints of CDK4/6 inhibitors: Palbociclib and ribociclib
R Costa1, R B Costa1, Sarah M Talamantes2
1Division of Hematology Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Purpose:
Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors such as palbociclib and ribociclib are associated with distinct adverse effects (AEs) compared to other targeted therapies. This meta-analysis of clinical trials summarizes these agents' toxicity profile.
Methods:
A librarian-guided literature search was conducted in March of 2017. The trials needed to have at least one of the study arms consisting of palbociclib or ribociclib monotherapy at currently FDA approved dose regimens. Heterogeneity across studies was analyzed using I2 statistics. Data were analyzed using random effects meta-analysis for absolute risks.
Results:
Seven randomized trials and 1,332 patients were included in our meta-analysis. There was evidence of significant heterogeneity between studies for serious AEs but not for death. The pooled absolute risk (AR) for all-causality serious AEs and treatment-related death were 16% and 0%, respectively. Patients treated with CDK 4/6 inhibitors had an AR of grade 3/4 neutropenia of 61%; neutropenic fever and infections were rare (1% and 3%, respectively). Grade 3/4 nausea, vomiting, and rash were rare. There was no significant correlation between age of patients at study entry and the risk of grade 3/4 neutropenia.
Conclusion:
Treatment with CDK 4/6 inhibitors is well tolerated and associated with a low risk of treatment-related deaths. There is an increased AR of grade 3/4 neutropenia but a low AR of associated infections.
Insights
Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are generally well-tolerated with a low risk of death. While grade 3/4 neutropenia is common, serious infections are rare in patients receiving these targeted therapies.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors represent a significant advancement in targeted cancer therapy.
- These agents, including palbociclib and ribociclib, are associated with a unique spectrum of adverse effects (AEs) compared to other targeted treatments.
- Understanding the toxicity profile of CDK4/6 inhibitors is crucial for optimizing patient management and treatment outcomes.
Purpose of the Study:
- To conduct a meta-analysis of clinical trials to summarize the toxicity profile of palbociclib and ribociclib monotherapy.
- To quantify the absolute risk (AR) of specific adverse events, including serious AEs and treatment-related deaths.
Main Methods:
- A systematic literature search was performed in March 2017, including randomized trials of palbociclib or ribociclib monotherapy at FDA-approved doses.
- Heterogeneity across studies was assessed using I-squared statistics.
- Random effects meta-analysis was employed to determine pooled absolute risks for various adverse events.
Main Results:
- Seven randomized trials encompassing 1,332 patients were analyzed.
- The pooled AR for all-causality serious AEs was 16%, with a 0% AR for treatment-related death.
- A high AR of 61% for grade 3/4 neutropenia was observed, while neutropenic fever and infections were infrequent (1% and 3%, respectively).
- Grade 3/4 nausea, vomiting, and rash were rare, and patient age did not correlate with the risk of grade 3/4 neutropenia.
Conclusions:
- CDK4/6 inhibitors demonstrate a favorable safety profile with a low incidence of treatment-related mortality.
- An elevated risk of grade 3/4 neutropenia is a notable AE, but it is associated with a low risk of subsequent infections.
- These findings support the tolerability of CDK4/6 inhibitors in clinical practice.
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