The effect of gastrectomy on regorafenib exposure and progression-free survival in patients with advanced gastrointestinal stromal tumours.

Aims: We investigated whether major gastrectomy influences the plasma exposure of regorafenib and treatment outcome.

Methods: Efficacy and pharmacokinetic data from 133 gastrointestinal stromal tumour patients included in a phase III trial were analysed. Patients were subdivided into 2 groups according to the extent of the gastrectomy (no/nonsignificant gastrectomy and major gastrectomy). Progression-free survival (PFS) on regorafenib was measured and regorafenib and its pharmacological active metabolites plasma exposure were measured.

Results: A total of 133 patient were included, of whom 27 underwent major gastrectomy. In patients with no/nonsignificant gastrectomy the median PFS was 145 (interquartile range 43-281) days. The PFS in patients with a major gastrectomy was 172 (interquartile range 57-280) days. Regorafenib pharmacokinetic samples were collected in 80 patients of which 19 patients with a major gastrectomy and 61 patients with no/nonsignificant gastric surgery. The average ± standard deviation total concentration of regorafenib including the metabolites M-2 and M-5 was 6.9 ± 1.53 μmol/L and 6.7 ± 1.56 μmol/L in patient with major gastrectomy and no/nonsignificant gastrectomy respectively.

Conclusion: Our study shows that major gastrectomy did not influence plasma exposure of regorafenib and metabolites. In addition, no difference in PFS between the subgroups was seen.