title: Efficacy and Safety of Regorafenib in Korean Patients with Advanced Gastrointestinal Stromal Tumor after Failure of Imatinib and Sunitinib: A Multicenter Study Based on the Management Access Program.
abstract: OBJECTIVE
  The aim of this study was to confirm the efficacy and safety of regorafenib for advanced gastrointestinal stromal tumors (GISTs) reported in the GRID phase III trial in Korean patients.
  
  
  METHODS
  Fifty-seven Korean patientswith advanced GISTwho experienced both imatinib and sunitinib failure were enrolled in the management access program between December 2012 and November 2013 and treated with regorafenib (160 mg orally once daily in a 3 weeks on/1 week off).
  
  
  RESULTS
  None of the patients achieved a complete or partial response while 25 patients (44%) showed stable disease for ≥ 12 weeks. With a median follow-up of 12.7 months (range, 0.2 to 27.6 months), the median progression-free survival and overall survival were 4.5 months (95% confidence interval [CI], 3.8 to 5.3) and 12.9 months (95% CI, 8.1 to 17.7), respectively. Interestingly, 15 patients (26%) experienced an exacerbation of their cancer-related symptoms (abdominal pain in eight and abdominal distension in five) during the rest period for regorafenib, but all were ameliorated upon the resumption of regorafenib. The most common grade 3 or 4 adverse event was a hand-foot skin reaction (25%). The regorafenib dose was reduced in 44 patients (77%) due to toxicity, which manifested mainly as a hand-foot skin reaction (n=31).
  
  
  CONCLUSIONS
  This study confirmed the efficacy and safety of regorafenib for advanced GIST after imatinib and sunitinib failure in Korean patients. Considering the exacerbation of the cancer-related symptoms observed during the rest periods, further exploration of the continuous dosing schedule of regorafenib is warranted in future clinical trials.
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Myoung Kyun
authors.initials: MK
authors.lastname: Son
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Min-Hee
authors.initials: MH
authors.lastname: Ryu
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Joon Oh
authors.initials: JO
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Seock-Ah
authors.initials: SA
authors.lastname: Im
authors.affiliation: Department of Internal Medicine, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Tae-Yong
authors.initials: TY
authors.lastname: Kim
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Baek-Yeol
authors.initials: BY
authors.lastname: Ryoo
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Sook Ryun
authors.initials: SR
authors.lastname: Park
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Yoon-Koo
authors.initials: YK
authors.lastname: Kang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage; D007211:Indoles / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011758:Pyrroles / Q000008:administration & dosage; D019233:Retreatment; D000077210:Sunitinib; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011758:Pyrroles; C559147:regorafenib; D000068877:Imatinib Mesylate; D000077210:Sunitinib
keywords: Failure to imatinib; Gastrointestinal stromal tumors; Management access program; Regorafenib; Sunitinib