ArticleClinical pharmacokinetics2016
Population Pharmacokinetic Model of Cabozantinib in Patients with Medullary Thyroid Carcinoma and Its Application to an Exposure-Response Analysis.
Article in Clinical pharmacokinetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Cabozantinib exposure-response analyses of efficacy and safety in patients with advanced hepatocellular carcinoma.Journal of pharmacokinetics and pharmacodynamics · 2019Trial
- Cabozantinib in Patients with Advanced Merkel Cell Carcinoma.The oncologist · 2018Trial
- Population exposure-response analysis of cabozantinib efficacy and safety endpoints in patients with renal cell carcinoma.Cancer chemotherapy and pharmacology · 2018Trial
- Population Pharmacokinetics of Cabozantinib: Updated Analyses Including Data in Combination With Atezolizumab in Patients With Castration-Resistant Prostate Cancer and Other Tumor Types.Clinical and translational science · 2026Article
- Sex differences in hepatic enzymes and transporters involved in pharmacokinetics.Liver research (Beijing, China) · 2025Review
- Cabozantinib Carries the Risk of Drug-Drug InteractionsCurrent drug metabolism · 2022Article
- Harnessing Clinical Trial and Real-World Data Towards an Understanding of Sex Effects on Drug Pharmacokinetics, Pharmacodynamics and Efficacy.Frontiers in pharmacology · 2022Review
- Physiologically Based Pharmacokinetic Modelling of Cabozantinib to Simulate Enterohepatic Recirculation, Drug-Drug Interaction with Rifampin and Liver Impairment.Pharmaceutics · 2021Article
- Identification of Enzymes Oxidizing the Tyrosine Kinase Inhibitor Cabozantinib: Cabozantinib Is Predominantly Oxidized by CYP3A4 and Its Oxidation Is Stimulated by cyt bBiomedicines · 2020Article
- Drug Exposure to Establish Pharmacokinetic-Response Relationships in Oncology.Clinical pharmacokinetics · 2020Review
- Synergistic Highly Potent Targeted Drug Combinations in Different Pheochromocytoma Models Including Human Tumor Cultures.Endocrinology · 2019Article
- Clinical Pharmacokinetics and Pharmacodynamics of Transarterial Chemoembolization and Targeted Therapies in Hepatocellular Carcinoma.Clinical pharmacokinetics · 2019Review
- A population pharmacokinetic model of cabozantinib in healthy volunteers and patients with various cancer types.Cancer chemotherapy and pharmacology · 2018Article
- Cabozantinib in the treatment of advanced renal cell carcinoma in adults following prior vascular endothelial growth factor targeted therapy: clinical trial evidence and experience.Therapeutic advances in urology · 2018Review
- Practical Recommendations for Therapeutic Drug Monitoring of Kinase Inhibitors in Oncology.Clinical pharmacology and therapeutics · 2017Review
- Clinical Pharmacokinetics and Pharmacodynamics of Cabozantinib.Clinical pharmacokinetics · 2017Review
- Practical management of adverse events associated with cabozantinib treatment in patients with renal-cell carcinoma.OncoTargets and therapy · 2017Review
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesCabozantinib is a tyrosine kinase inhibitor approved in the USA and EU for the treatment of patients with progressive, metastatic medullary thyroid cancer (MTC). The indicated cabozantinib dose is 140 mg/day, with dose modifications allowed for patients who develop adverse events (AEs). The analysis objective was to develop a population pharmacokinetic (PopPK) model in MTC patients and to use the model for exposure-response (ER) analysis of dose modifications.
methodsA PopPK model for cabozantinib was developed using data from three clinical trials (2079 evaluations from 289 patients), including a randomized, double-blind, placebo-controlled phase III study of patients with progressive, metastatic MTC. The PopPK model predictions [model-predicted steady-state area under the plasma concentration-time curve (AUCss,pred)] were used for an ER analysis of the time to first dose modification.
resultsThe final PopPK model was a one-compartment model with first-order absorption and first-order elimination. Estimated cabozantinib apparent oral clearance (CL/F) and apparent volume of distribution (V c/F) were 106 L/day [±2.98 % relative standard error (RSE)] (males) and 349 L (±2.73 % RSE), respectively. CL/F was reduced by 22 % (to 83 L/day) in females. Sex and body mass index (BMI) were significant covariates that combined contributed 15 % to the variability in cabozantinib CL/F, but did not warrant dose adjustment. Higher cabozantinib AUCss,pred was correlated to an increased risk of early dose modification and a lower average dose through to Day 85. Early cabozantinib dose modification was not associated with a reduction in progression-free survival (PFS).
conclusionA PopPK model was developed for cabozantinib pharmacokinetics in MTC patients. Higher cabozantinib exposure was associated with earlier first dose modification and a lower average administered dose through to Day 85. Early first dose modification did not appear to impact PFS.
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Registered trials
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