Exposure-response analysis and simulation of lenvatinib safety and efficacy in patients with radioiodine-refractory differentiated thyroid cancer.
Cancer Chemother Pharmacol
; 82(6): 971-978, 2018 12.
Article
en En
| MEDLINE
| ID: mdl-30244318
ABSTRACT
PURPOSE:
Once-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.METHODS:
A 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.RESULTS:
The 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.CONCLUSIONS:
Treatment 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.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Compuestos de Fenilurea
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Quinolinas
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Neoplasias de la Tiroides
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos
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Modelos Biológicos
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Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Año:
2018
Tipo del documento:
Article
País de afiliación:
Japón