Are novel oral oncolytics underdosed in obese patients?

LS Lin, EKO van der Meer, Neeltje Steeghs, JH Beijnen, Alwin D R Huitema*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Purpose
Data on the effects of obesity on drug exposure of oral targeted oncolytics is scarce. Therefore, the aim of this study was to investigate the influence of body weight and body mass index (BMI) on trough levels of oral oncolytics with an exposure–response relationship. The oral oncolytics of interest were abiraterone, alectinib, cabozantinib, crizotinib, imatinib, pazopanib, sunitinib and trametinib.

Methods
This retrospective cohort study included patients treated with the selected oral oncolytics at the standard dose, with a measured trough level at steady state and with available body weight. The Spearman’s correlation test was used to determine the correlation between body weight and trough levels. The Fisher’s exact text was used to compare the frequency of inadequate trough levels between BMI categories.

Results
1265 patients were included across the different oral oncolytics. A negative correlation coefficient was observed between weight and trough levels for crizotinib (n = 75), imatinib (n = 201) and trametinib (n = 310), respectively, ρ = − 0.41, ρ = − 0.24 and ρ = − 0.23, all with a p-value < 0.001. For crizotinib, a higher percentage of patients with a body weight > 100 kg had inadequate trough levels. No statistically significant differences were observed in the frequency of inadequate trough levels between BMI categories.

Conclusion
Higher body weight was only correlated with lower plasma trough levels for crizotinib, imatinib, and trametinib. Therefore, patients with a high body weight may require dose escalation to obtain adequate target levels when treated with these oral oncolytics.
Original languageEnglish
Pages (from-to)129-136
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Volume93
Issue number2
DOIs
Publication statusPublished - Feb 2024

Keywords

  • Body weight
  • Exposure-response relationship
  • Obesity
  • Targeted therapy
  • Therapeutic drug monitoring

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