Highlights
- •Seventy-five percent of patients had an imatinib exposure below the minimum plasma concentration threshold of 1100 ng/mL.
- •In 62% of these patients, the imatinib dose was increased to either 600 mg or 800 mg.
- •This PK-guided dose increase was successful in 63% of patients.
- •Therapeutic drug monitoring of imatinib is feasible in clinical practice.
Abstract
Aim
Higher imatinib exposure is correlated with longer time to progression, while the
variability in exposure is high. This provides a strong rationale for therapeutic
drug monitoring, which has therefore been implemented in routine clinical practice
in our institute. The aim of this study is to evaluate whether pharmacokinetically
(PK)-guided dose increases are feasible in daily clinical practice and result in an
improved exposure (Cmin≥1100 ng/mL) and longer progression-free survival (PFS).
Methods
This retrospective study included all patients with a gastrointestinal stromal tumour
(GIST) in the Netherlands Cancer Institute who started imatinib treatment at a dose
of 400 mg and of whom PK plasma samples were available. Of these patients, minimum
plasma concentrations (Cmin) of imatinib, frequency and successfulness of PK-guided dose increases and PFS in
the palliative treatment setting were analysed.
Results
In total, 169 consecutive patients were included, of whom 1402 PK samples were collected.
In 126 patients (75%), Cmin was below the efficacy threshold of 1100 ng/mL. In 78 of these patients (62%), a
PK-guided dose increase was performed, which was successful in 49 patients (63%).
PFS was similar in patients with and without imatinib dose increase. However, due
to the small number of patients with progressive disease, no definite conclusions
on the effect on PFS could yet be drawn.
Conclusion
This is the largest cohort evaluating PK-guided dose increases of imatinib in patients
with GIST in routine clinical practice and demonstrating its feasibility. PK-guided
dose increases should be applied to optimise exposure in the significant subset of
patients with a low Cmin.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: July 17, 2020
Accepted:
May 19,
2020
Received in revised form:
May 13,
2020
Received:
April 15,
2020
Identification
Copyright
© 2020 Elsevier Ltd. All rights reserved.
