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Purpose <p>Trametinib, a MEK1/2 inhibitor, has emerged as a promising treatment for pediatric patients with low-grade gliomas (LGG). However, trametinib exhibits significant inter-individual pharmacokinetic (PK) variability, and studies in adults demonstrated an exposure-efficacy relationship. This study aimed to evaluate the PK profile of trametinib in pediatric routine care and explore potential exposure-outcome relationships.</p> Methods <p>We analyzed PK data from 65 blood samples from 19 children receiving trametinib, either as single agent or in combination with dabrafenib. A trough concentration (Cmin) range of 8–15&#xa0;ng/mL was considered, based on average exposure reported in the largest pediatric study.</p> Results <p>The mean Cmin was 8.82&#xa0;ng/ml, with 64.6% of samples falling within the predefined target range, while 35.4% were below it. Regarding tolerance, 84.2% of patients experienced treatment-related toxicities, predominantly skin and subcutaneous tissue disorders. Efficacy data were limited.</p> Conclusion <p>These findings underscore the necessity of therapeutic drug monitoring in pediatric patients to optimize treatment efficacy and minimize toxicity, highlighting trametinib’s potential for personalized dosing strategies in this population.</p>

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Real-world pharmacokinetics of trametinib in pediatric low-grade glioma

  • 期刊论文

  • 发表日期：

    2025年2月25日

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  • Laurie Pagnot,
  • Isaline Granger,
  • Jérôme Guitton,
  • Bertrand Favier,
  • Antony Ceraulo,
  • Cécile Faure-Conter,
  • Pierre Leblond,
  • Michael Philippe

摘要

Purpose

Trametinib, a MEK1/2 inhibitor, has emerged as a promising treatment for pediatric patients with low-grade gliomas (LGG). However, trametinib exhibits significant inter-individual pharmacokinetic (PK) variability, and studies in adults demonstrated an exposure-efficacy relationship. This study aimed to evaluate the PK profile of trametinib in pediatric routine care and explore potential exposure-outcome relationships.

Methods

We analyzed PK data from 65 blood samples from 19 children receiving trametinib, either as single agent or in combination with dabrafenib. A trough concentration (Cmin) range of 8–15 ng/mL was considered, based on average exposure reported in the largest pediatric study.

Results

The mean Cmin was 8.82 ng/ml, with 64.6% of samples falling within the predefined target range, while 35.4% were below it. Regarding tolerance, 84.2% of patients experienced treatment-related toxicities, predominantly skin and subcutaneous tissue disorders. Efficacy data were limited.

Conclusion

These findings underscore the necessity of therapeutic drug monitoring in pediatric patients to optimize treatment efficacy and minimize toxicity, highlighting trametinib’s potential for personalized dosing strategies in this population.