title: Regorafenib for advanced gastrointestinal stromal tumors following imatinib and sunitinib treatment: a subgroup analysis evaluating Japanese patients in the phase III GRID trial.
abstract: BACKGROUND
  The randomized, double-blind, placebo-controlled GRID trial tested the oral multikinase inhibitor regorafenib in 199 patients with advanced gastrointestinal stromal tumors (GIST) following failure of at least imatinib and sunitinib, and showed a significant improvement in progression-free survival (PFS) versus placebo [hazard ratio (HR) 0.27; 95 % confidence interval (CI) 0.19-0.39; p < 0.0001].
  
  
  METHODS
  A subgroup analysis of Japanese patients in the GRID study was performed to compare the efficacy and safety of oral regorafenib 160 mg once daily with matching placebo, in combination with best supportive care. The primary study endpoint was progression-free survival (PFS); safety was evaluated through the incidence of adverse events (AEs).
  
  
  RESULTS
  Seventeen Japanese patients were randomized to regorafenib (n = 12) or placebo (n = 5). Patient demographics were consistent with those of the overall study population. PFS was significantly longer with regorafenib than placebo (HR 0.08; 95 % CI 0.02-0.45; p = 0.000164). Centrally assessed disease control rates were 58 % and 20 % in the regorafenib and placebo groups, respectively (p = 0.080796). Treatment-related adverse events (AEs) were reported in all regorafenib-treated patients and 60 % of placebo recipients; the most frequent AE was hand-foot skin reaction (HFSR) (92 % versus 20 %, respectively).
  
  
  CONCLUSIONS
  Regorafenib showed efficacy and a manageable safety profile in Japanese patients with advanced GIST, consistent with the overall GRID study population. AEs, such as HFSR and maculopapular rash, were observed more frequently in Japanese patients. Although dose modification was frequently reported, only one patient with hepatic failure discontinued regorafenib because of AEs.
authors: Cancer Center, Hokkaido University Hospital, Kita 14 Nishi 5, Kita-ku, Sapporo, Hokkaido, 060-8648, Japan. ykomatsu@ac.cyberhome.ne.jp.
authors: Yoshito
authors: Y
authors: Komatsu
authors: National Cancer Center Hospital East, Kashiwa, Japan.
authors: Toshihiko
authors: T
authors: Doi
authors: Department of Oncology and Gastroenterology, Nagoya Second Red Cross Hospital, Nagoya, Japan.
authors: Akira
authors: A
authors: Sawaki
authors: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors: Tatsuo
authors: T
authors: Kanda
authors: Gastrointestinal Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors: Yasuhide
authors: Y
authors: Yamada
authors: Global Clinical Development, Oncology, Ophthalmology and Neurology, Bayer Pharma AG, Berlin, Germany.
authors: Iris
authors: I
authors: Kuss
authors: Ludwig Cancer Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
authors: George D
authors: GD
authors: Demetri
authors: Department of Surgery, National Cancer Center Hospital East, Kashiwa, Japan.
authors: Toshirou
authors: T
authors: Nishida
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D044466:Asian People; D004311:Double-Blind Method; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000208:ethnology / Q000473:pathology; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000208:ethnology / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D008875:Middle Aged; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use; D000077210:Sunitinib; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D010671:Phenylurea Compounds; D011725:Pyridines; D011758:Pyrroles; C559147:regorafenib; D000068877:Imatinib Mesylate; D000077210:Sunitinib
keywords: Gastrointestinal stromal tumor; Hand–foot syndrome; Hypertension; Japanese; Regorafenib
references: Jpn J Clin Oncol. 2010 Mar;40(3):194-202
references: 19897852
references: Gastric Cancer. 2009;12(4):175-88
references: 20047122
references: Int J Cancer. 2011 Jul 1;129(1):245-55
references: 21170960
references: Cancer Treat Rev. 2011 Aug;37(5):373-84
references: 21195552
references: Oncology. 2011;80(5-6):395-405
references: 21829041
references: Nat Rev Cancer. 2011 Dec;11(12):865-78
references: 22089421
references: Discov Med. 2012 May;13(72):357-67
references: 22642917
references: Lancet. 2013 Jan 26;381(9863):295-302
references: 23177515
references: Jpn J Clin Oncol. 2013 Jun;43(6):616-28
references: 23630366
references: Invest New Drugs. 2015 Jun;33(3):740-50
references: 25213161
references: Lancet Oncol. 2009 Jan;10(1):25-34
references: 19095497
references: Clin Cancer Res. 2007 Jan 1;13(1):170-81
references: 17200352
references: Int J Cancer. 2005 Nov 1;117(2):289-93
references: 15900576
references: Cancer. 2005 Feb 15;103(4):821-9
references: 15648083
references: J Natl Compr Canc Netw. 2007 Jul;5 Suppl 2:S1-29; quiz S30
references: 17624289
references: J Natl Compr Canc Netw. 2010 Apr;8 Suppl 2:S1-41; quiz S42-4
references: 20457867