LAUSR

e22511 Background: Gastrointestinal stromal tumour (GIST) is one of the most common soft tissue sarcoma subtypes. Regorafenib is the approved third line treatment after imatinib and sunitinib. Often GIST patients have an altered gastro-intestinal tract due to resection of the primary tumour. Gastric surgery may influence the exposure of orally administered TKIs. We investigated whether major gastrectomy influences the plasma exposure of regorafenib and treatment outcome. Methods: Efficacy and pharmacokinetic data from 133 GIST patients included in a phase III trial were analysed. Patients were subdivided into two groups according to the extent of the gastrectomy (no/non-significant gastrectomy and major gastrectomy). Progression free survival (PFS) on regorafenib was measured and regorafenib and its pharmacological active metabolites plasma exposure (Cav) were measured. Results: A total of 133 patient were included of which 27 underwent major gastrectomy. In patients with no/non significant gastrectomy the median PFS was 145 (IQR 43-281) days. The PFS in patients with a major gastrectomy was 172 (IQR 57-280) days. Regorafenib pharmacokinetic samples were collected in 80 patients of which 19 patients with a major gastrectomy and 61 patients with no/ non-significant gastric surgery. The average free aggregate concentration of regorafenib including the metabolites M-2 and M-5 was 6.9 µmol/L (CV% 44.5) and 6.7 µmol/L (CV% 46.5) in patient with major gastrectomy and no or non significant gastrectomy respectively. Conclusions: Our study shows that major gastrectomy did not influence plasma exposure of regorafenib and metabolites. In addition, no difference in progression free survival between the subgroups was seen.