ArticleCPT: pharmacometrics & systems pharmacology2019
Modeling Exposure-Driven Adverse Event Time Courses in Oncology Exemplified by Afatinib.
Article in CPT: pharmacometrics & systems pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
9 citing papers in PubMed.
- Mobocertinib Dose Rationale in Patients with Metastatic NSCLC with EGFR Exon 20 Insertions: Exposure-Response Analyses of a Pivotal Phase I/II Study.Clinical pharmacology and therapeutics · 2022Trial
- Novel Drug-Disease Modeling Framework for Oncology Benefit-Risk Evaluation: Application to Tusamitamab Ravtansine.CPT: pharmacometrics & systems pharmacology · 2026Article
- Exposure-driven tolerance modeling of efpeglenatide-induced nausea or vomiting using repeated time-to-event analysis: implications for dose-escalation strategies.Frontiers in pharmacology · 2026Article
- A Step-by-Step Workflow for Performing In Silico Clinical Trials With Nonlinear Mixed Effects Models.CPT: pharmacometrics & systems pharmacology · 2025Article
- A tutorial on pharmacometric Markov models.CPT: pharmacometrics & systems pharmacology · 2025Article
- Dermatologic Toxicities of Targeted Therapy and Immunotherapy in Head and Neck Cancers.Frontiers in oncology · 2021Review
- Phase I study of afatinib plus bevacizumab in patients with advanced non-squamous non-small cell lung cancer harboringTranslational lung cancer research · 2021Article
- Evaluation of patient-reported severity of hand-foot syndrome under capecitabine using a Markov modeling approach.Cancer chemotherapy and pharmacology · 2020Observational
- Analysis of Longitudinal-Ordered Categorical Data for Muscle Spasm Adverse Event of Vismodegib: Comparison Between Different Pharmacometric Models.CPT: pharmacometrics & systems pharmacology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Models were developed to characterize the relationship between afatinib exposure and diarrhea and rash/acne adverse event (AE) trajectories, and their predictive ability was assessed. Based on pooled data from seven phase II/III clinical studies including 998 patients, mixed-effects models for ordered categorical data were applied to describe daily AE severity. Clinical trial simulation aided by trial execution models was used for internal and external model evaluation. The final exposure-safety model consisted of longitudinal logistic regression models with first-order Markov elements for both AEs. Drug exposure was included as daily area under the concentration-time curve (AUC), and drug effects on the AEs were correlated. Clinical trial simulation allowed adequate prediction of maximum AE grades and AE severity time courses but overestimated the proportion of AE-dependent dose reductions and discontinuations. Both diarrhea and rash/acne were correlated with afatinib exposure. The developed modeling framework allows a prospective comparison of dosing strategies and study designs with respect to safety.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.