Therapeutic drug monitoring of small molecule kinase inhibitors in oncology in a real-world cohort study: does age matter?

Abstract

Aim: Pharmacokinetics of small molecule kinase inhibitors (KIs) used in cancer treatment may alter with increasing age, but results are conflicting. This study aims to compare exposure to KIs between older and younger patients (≥70 and <70 years) in clinical practice.

Methods: KI plasma concentrations of routinely treated patients were measured using validated assays. Calculated trough concentrations were compared in both age groups. For KIs with a clinically meaningful target concentration (erlotinib, imatinib, pazopanib, sunitinib and vemurafenib), influence of older age on target attainment was assessed.

Results: We analysed 616 samples from 454 patients (median age: 61; range 20-93 years), treated with dabrafenib (n = 105), erlotinib (n = 49), imatinib (n = 165), pazopanib (n = 63), sunitinib (n = 87), trametinib (n = 95) and vemurafenib (n = 52). Older age did not significantly influence exposure to erlotinib, imatinib, pazopanib, sunitinib, trametinib and vemurafenib. Elderly patients had significantly higher dabrafenib trough concentrations than younger patients (P = 0.02; 62 ng ml-1 (coefficient of variation [CV] 41%), vs. 53 ng ml-1 (CV 46%), respectively). For KIs with a predefined target concentration, 68% of older and 61% of younger patients reached target.

Conclusions: In this real-world study, exposure to most included KIs was comparable in older and younger patients, except for dabrafenib, which showed higher exposure in older patients. In the absence of an absolute target for this KI, clinical relevance remains unclear. For all other included KIs, our data suggest no clinically relevant influence of older age on KI exposure.

Keywords: anticancer drugs; elderly; pharmacokinetics; therapeutic drug monitoring.

© 2018 The British Pharmacological Society.

Figures

Figure 1

Box‐plots of KI trough concentrations per age group, with the dashed lines representing the target concentration, if applicable. aCombined trough concentrations of sunitinib and N‐desethyl‐sunitinib. bTarget trough concentration depicted as ×103 ng ml−1, i.e. in μg ml−1

Figure 2

KI trough target concentrations vs. age as a continuous variable, with dots representing calculated KI trough concentration per patient, and the line fitted using a linear model. aCombined trough concentrations of sunitinib and N‐desethyl‐sunitinib. bTarget trough concentration depicted as ×103 ng ml−1, i.e. in μg ml−1