Aims We investigated whether major gastrectomy influences the plasma exposure of regorafenib and treatment outcome. Methods Efficacy and pharmacokinetic data from 133 gastrointestinal stromal... Show moreAims 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 mu mol/L and 6.7 +/- 1.56 mu mol/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. Show less
