title: Phase II study of ipilimumab monotherapy in Japanese patients with advanced melanoma.
abstract: OBJECTIVE
  Ipilimumab is designed to block cytotoxic T-lymphocyte antigen-4 to augment antitumor T cell responses. In studies of predominantly Caucasian patients with advanced melanoma, ipilimumab was associated with durable response, long-term survival benefit, and a manageable safety profile. This phase II study assessed the safety of ipilimumab in Japanese patients with unresectable stage III or IV melanoma.
  
  
  METHODS
  Patients received ipilimumab 3 mg/kg every 3 weeks for four doses. The database lock for the original analysis was in August 2014. Overall survival, progression-free survival, and data on deaths were based on an updated, follow-up analysis (database lock April 2015).
  
  
  RESULTS
  Data are reported from 20 patients. Fifteen patients (75 %) received all four doses of ipilimumab during induction. Twelve patients (60 %) had at least one drug-related adverse event (AE), and no patients discontinued due to a drug-related AE. There were no deaths related to study drug. The most common drug-related AEs were rash (n = 7), pyrexia (n = 3), increased aspartate aminotransferase (AST; n = 3), and increased alanine aminotransferase (ALT; n = 3). Twelve patients (60 %) reported immune-related AEs (irAEs); most frequent were skin (n = 9) and liver (n = 3) disorders. Grade 3 irAEs were ALT and AST elevation (n = 2) and diabetes mellitus (n = 1). Two patients had a partial response and two had stable disease, yielding a 20 % disease control rate. Median overall survival and progression-free survival were 8.71 and 2.74 months, respectively.
  
  
  CONCLUSIONS
  Ipilimumab 3 mg/kg had a manageable AE profile in this Japanese patient population with clinical outcomes similar to that in Caucasian patients. CLINICALTRIALS.
  NCT01990859.
authors.affiliation: Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Yamazaki
authors.affiliation: Dermatology Division, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kiyohara
authors.affiliation: Department of Dermatology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Uhara
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Fukushima
authors.affiliation: Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Uchi
authors.affiliation: Department of Dermatology, University of Yamanashi Hospital, Yamanashi, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Shibagaki
authors.affiliation: Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Tsutsumida
authors.affiliation: Dermatology Division, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yoshikawa
authors.affiliation: Department of Dermatology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Okuyama
authors.affiliation: Research and Development, Bristol-Myers K.K., 6-5-1, Nishishinjuku, Shinjuku-ku, Tokyo, 1631328, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Research and Development, Bristol-Myers K.K., 6-5-1, Nishishinjuku, Shinjuku-ku, Tokyo, 1631328, Japan. takuto0806@gmail.com.
authors.forename: T
authors.initials: T
authors.lastname: Tokudome
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D000917:Antibody Formation; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors / Q000276:immunology; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D018572:Disease-Free Survival; D003875:Drug Eruptions / Q000209:etiology; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D005334:Fever / Q000139:chemically induced; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D000074324:Ipilimumab; D007564:Japan; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D007155:Immunologic Factors; D000074324:Ipilimumab
keywords: Immune-checkpoint inhibitor; Ipilimumab; Japanese patients; Melanoma; Phase II study