title: Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma: Japanese subgroup analysis of the REACH trial.
abstract: BACKGROUND
  REACH evaluated ramucirumab in the second-line treatment of patients with advanced hepatocellular carcinoma. In the intent-to-treat population (n = 565), a significant improvement in overall survival (OS) was not observed. In patients with an elevated baseline α-fetoprotein (AFP) level (400 ng/mL or greater), an improvement in OS was demonstrated. An analysis of the Japanese patients in REACH was performed.
  
  
  METHODS
  An analysis was performed with the subset of the intent-to-treat population enrolled in Japan (n = 93).
  
  
  RESULTS
  The median OS was 12.9 months for the ramucirumab arm (n = 45) and 8.0 months for the placebo arm (n = 48) [hazard ratio (HR) 0.621 (95 % confidence interval (CI) 0.391-0.986); P = 0.0416]. The median progression-free survival was 4.1 months for the ramucirumab arm and 1.7 months for the placebo arm [HR 0.449 (95 % CI 0.285-0.706); P = 0.0004]. The objective response rates were 11 % for the ramucirumab arm and 2 % for the placebo arm (P = 0.0817). The grade 3 or higher treatment-emergent adverse events occurring in more than 5 % of patients with a higher incidence for the ramucirumab arm (n = 44) than for the placebo arm (n = 47) were ascites (7% vs 2 %), hypertension (7 % vs 2 %), and cholangitis (7 % vs 0 %). In patients with a baseline AFP level of 400 ng/mL or greater, the median OS was 12.9 months for the ramucirumab arm (n = 20) and 4.3 months for the placebo arm (n = 22) [HR 0.464 (95 % CI 0.232-0.926); P = 0.0263].
  
  
  CONCLUSIONS
  In the Japanese patients in REACH, ramucirumab treatment improved OS, including in patients with a baseline AFP level of 400 ng/mL or greater; improvements in progression-free survival and objective response rate were also demonstrated. The safety profile of ramucirumab was acceptable and well tolerated in Japanese patients. ClinicalTrials.gov identifier NCT01140347.
authors.affiliation: Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan. m-kudo@med.kinki.ac.jp.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kudo
authors.affiliation: Kyoto University Hospital, Kyoto, Japan.
authors.forename: Etsuro
authors.initials: E
authors.lastname: Hatano
authors.affiliation: Kanagawa Cancer Center, Yokohama, Kanagawa, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ohkawa
authors.affiliation: Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Fujii
authors.affiliation: Aso Iizuka Hospital, Fukuoka, Japan.
authors.forename: Akihide
authors.initials: A
authors.lastname: Masumoto
authors.affiliation: Kyorin University School of Medicine Hospital, Tokyo, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Furuse
authors.affiliation: National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Wada
authors.affiliation: The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishii
authors.affiliation: Kyoundo Hospital, Sasaki Institute, Tokyo, Japan.
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Obi
authors.affiliation: Kanazawa University Hospital, Ishikawa, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
authors.affiliation: Saga-Ken Medical Centre Koseikan, Saga, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Kawazoe
authors.affiliation: Chiba University Hospital, Chiba, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokosuka
authors.affiliation: National Cancer Center Hospital East, Chiba, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Sendai Medical Center, Sendai, Miyagi, Japan.
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Ukai
authors.affiliation: Kochi Health Sciences Center, Kochi, Japan.
authors.forename: Sojiro
authors.initials: S
authors.lastname: Morita
authors.affiliation: Kagawa University Hospital, Takamatsu, Kagawa, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Tsuji
authors.affiliation: Osaka University Hospital, Osaka, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kudo
authors.affiliation: Tokushima University Hospital, Tokushima, Japan.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Shimada
authors.affiliation: Osaka Red Cross Hospital, Osaka, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Osaki
authors.affiliation: The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Tateishi
authors.affiliation: Kurume University Medical Center, Fukuoka, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Sugiyama
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Paolo Benjamin
authors.initials: PB
authors.lastname: Abada
authors.affiliation: Eli Lilly and Company, Bridgewater, NJ, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Yang
authors.affiliation: National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Okusaka
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Andrew Xiuxuan
authors.initials: AX
authors.lastname: Zhu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077157:Sorafenib; D016896:Treatment Outcome; D000509:alpha-Fetoproteins / Q000032:analysis; D000096662:Ramucirumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009536:Niacinamide; D010671:Phenylurea Compounds; D000077157:Sorafenib; D000509:alpha-Fetoproteins; D000096662:Ramucirumab
keywords: Clinical trial; Japan; Liver neoplasms; Vascular endothelial growth factor receptor 2; α-Fetoprotein