ArticleCancer chemotherapy and pharmacology2018
Exposure-response analysis and simulation of lenvatinib safety and efficacy in patients with radioiodine-refractory differentiated thyroid cancer.
Article in Cancer chemotherapy and pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Population pharmacokinetic-pharmacodynamic modeling of serum biomarkers as predictors of tumor dynamics following lenvatinib treatment in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC).CPT: pharmacometrics & systems pharmacology · 2024Trial
- A Randomized Study of Lenvatinib 18 mg vs 24 mg in Patients With Radioiodine-Refractory Differentiated Thyroid Cancer.The Journal of clinical endocrinology and metabolism · 2022Trial
- Characterization and Management of Adverse Reactions in Patients with Advanced Endometrial Carcinoma Treated with Lenvatinib Plus Pembrolizumab.The oncologist · 2021Trial
- Target Attainment and Clinical and Biochemical Parameters Associated with the Pharmacokinetics of 12 Tyrosine Kinase Inhibitors.Clinical pharmacokinetics · 2026Article
- Lenvatinib in radioiodine-refractory differentiated thyroid cancer: a real-world institutional analysis.Endocrine journal · 2026Article
- Prognostic factors of lenvatinib plus pembrolizumab therapy for advanced or recurrent endometrial cancer: analysis of a multicenter cohort study in Japan.International journal of clinical oncology · 2025Observational
- Lenvatinib as an urgent initial therapy in thyroid cancer with remarkable laryngotracheal invasion.European thyroid journal · 2025Article
- Therapeutic Drug Monitoring of Kinase Inhibitors in Oncology.Clinical pharmacokinetics · 2023Review
- Lenvatinib for the Treatment of Radioiodine-Refractory Differentiated Thyroid Cancer: Treatment Optimization for Maximum Clinical Benefit.The oncologist · 2022Review
- Lenvatinib dose, efficacy, and safety in the treatment of multiple malignancies.Expert review of anticancer therapy · 2022Review
- Therapeutic drug monitoring of oral targeted antineoplastic drugs.European journal of clinical pharmacology · 2021Review
- Pharmacodynamic analysis of hypertension caused by lenvatinib using real-world postmarketing surveillance data.CPT: pharmacometrics & systems pharmacology · 2021Article
- Article
- The multiple-kinase inhibitor lenvatinib inhibits the proliferation of acute myeloid leukemia cells.Animal models and experimental medicine · 2019Article
Corrections and comments
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Authors and funding
6 authors.
Funding
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Abstract
purposeOnce-daily lenvatinib 24 mg is the approved dose for radioiodine-refractory differentiated thyroid cancer. In a phase 3 trial with lenvatinib, the starting dose of 24 mg was associated with a relatively high incidence of adverse events that required dose reductions. We used an exposure-response model to investigate the risk-benefit of different dosing regimens for lenvatinib.
methodsA population pharmacokinetics/pharmacodynamics modeling analysis was used to simulate the potential benefit of lower starting doses to retain efficacy with improved safety. The seven lenvatinib regimens tested were: 24 mg; and 20 mg, 18 mg, and 14 mg, all with or without up-titration to 24 mg. Exposure-response models for efficacy and safety were created using a 24-week time course.
resultsThe approved dose of lenvatinib at 24 mg, predicted the best efficacy. However, the lenvatinib dosing regimens of 14 mg with up-titration or 18 mg without up-titration potentially provides comparable efficacy (objective response rate at 24 weeks) and a better safety profile.
conclusionsTreatment with lenvatinib at starting doses lower than the approved once-daily 24 mg dose could provide comparable antitumor efficacy and a similar or better safety profile. Based on the results from this modeling and simulation study, a comparator dose of lenvatinib 18 mg without up-titration was selected for evaluation in a clinical trial.
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