Therapeutic drug monitoring of imatinib in patients with gastrointestinal stromal tumours - Results from daily clinical practice.

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 (C≥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 (C) 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%), C 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 C.