PMID- 30447539
OWN - NLM
STAT- MEDLINE
DCOM- 20191003
LR  - 20220409
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 105
DP  - 2018 Dec
TI  - Efficacy and safety of nivolumab in combination with ipilimumab in Japanese 
      patients with advanced melanoma: An open-label, single-arm, multicentre phase II 
      study.
PG  - 114-126
LID - S0959-8049(18)31395-9 [pii]
LID - 10.1016/j.ejca.2018.09.025 [doi]
AB  - AIM: The aim of the study was to evaluate the efficacy and safety of nivolumab 
      combined with ipilimumab in treatment-naive Japanese patients with advanced 
      melanoma. METHODS: In this multicentre, single-arm study, treatment-naive 
      Japanese patients with unresectable stage III/IV or recurrent melanoma received 
      nivolumab (1 mg/kg) plus ipilimumab (3 mg/kg) every 3 weeks for four doses, 
      followed by biweekly doses of nivolumab (3 mg/kg). The primary end-point was 
      centrally assessed objective response rate (ORR). Secondary end-points included 
      overall survival (OS), progression-free survival (PFS), disease control rate and 
      safety. RESULTS: The subtypes of the thirty patients enrolled were: 12, mucosal; 
      eight, non-acral cutaneous; seven, acral; two, uveal and one, unknown primary 
      melanoma. The ORR was 43.3% (95% confidence interval [CI]: 25.5, 62.6) with 
      central and local assessment. The centrally and locally assessed disease control 
      rate (95% CI) were 73.3% (54.1, 87.7) and 86.7% (69.3, 96.2), respectively. At 
      the median follow-up period of 14.1 months (range 5.2-27.7), median OS and 
      centrally assessed PFS were not reached. OS (95% CI) at 6, 12, 18 and 24 months 
      was 93.3% (75.9, 98.3), 83.3% (64.5, 92.7), 72.9% (50.0, 86.5) and 65.6% (40.4, 
      82.2), respectively. Treatment-related adverse events (AEs) occurred in all 
      patients. Grade III-IV and serious AEs occurred, mostly during the combination 
      phase, in 23 (76.7%) and 20 (66.7%) patients, respectively. No treatment-related 
      deaths occurred. CONCLUSIONS: This study confirmed the efficacy and safety of 
      nivolumab plus ipilimumab in treatment-naive Japanese patients with advanced 
      melanoma including rare subtypes. Incidence rates for grade III-IV AEs were high 
      but manageable with appropriate medical attention and treatment. TRIAL 
      REGISTRATION: JapicCTI-152869.
CI  - Copyright (c) 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.
FAU - Namikawa, Kenjiro
AU  - Namikawa K
AD  - Department of Dermatologic Oncology, National Cancer Center Hospital, 5-1-1 
      Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. Electronic address: knamikaw@ncc.go.jp.
FAU - Kiyohara, Yoshio
AU  - Kiyohara Y
AD  - Dermatology Division, Shizuoka Cancer Center Hospital, 1007 Shimonagakubo, 
      Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan. Electronic address: 
      y.kiyohara@scchr.jp.
FAU - Takenouchi, Tatsuya
AU  - Takenouchi T
AD  - Department of Dermatology, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-cho, 
      Niigata 961-8566, Japan. Electronic address: tatsuya@niigata-cc.jp.
FAU - Uhara, Hisashi
AU  - Uhara H
AD  - Department of Dermatology, Shinshu University School of Medicine, 3-1-1 Asahi, 
      Matsumoto, Nagano 390-8621, Japan. Electronic address: uharah@sapmed.ac.jp.
FAU - Uchi, Hiroshi
AU  - Uchi H
AD  - Department of Dermatology, Graduate School of Medical Sciences, Kyushu 
      University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic 
      address: uchihir@dermatol.med.kyushu-u.ac.jp.
FAU - Yoshikawa, Shusuke
AU  - Yoshikawa S
AD  - Dermatology Division, Shizuoka Cancer Center Hospital, 1007 Shimonagakubo, 
      Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan. Electronic address: 
      s.yoshikawa@scchr.jp.
FAU - Takatsuka, Sumiko
AU  - Takatsuka S
AD  - Department of Dermatology, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-cho, 
      Niigata 961-8566, Japan. Electronic address: sumiko-ta@niigata-cc.jp.
FAU - Koga, Hiroshi
AU  - Koga H
AD  - Department of Dermatology, Shinshu University School of Medicine, 3-1-1 Asahi, 
      Matsumoto, Nagano 390-8621, Japan. Electronic address: koga@shinshu-u.ac.jp.
FAU - Wada, Naoko
AU  - Wada N
AD  - Department of Dermatology, Graduate School of Medical Sciences, Kyushu 
      University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic 
      address: w-naoco@med.kyushu-u.ac.jp.
FAU - Minami, Hironobu
AU  - Minami H
AD  - Department Medical Oncology/Hematology, Kobe University Graduate School of 
      Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan. Electronic 
      address: hminami@med.kobe-u.ac.jp.
FAU - Hatsumichi, Masahiro
AU  - Hatsumichi M
AD  - Ono Pharmaceutical Co. Ltd., 1-8-2 Kyutaromachi, Chuo-ku, Osaka 541-8564, Japan. 
      Electronic address: hatsumichi@ono.co.jp.
FAU - Asada, Suguru
AU  - Asada S
AD  - Ono Pharmaceutical Co. Ltd., 1-8-2 Kyutaromachi, Chuo-ku, Osaka 541-8564, Japan. 
      Electronic address: s.asada@ono.co.jp.
FAU - Namba, Yoshinobu
AU  - Namba Y
AD  - Ono Pharmaceutical Co. Ltd., 1-8-2 Kyutaromachi, Chuo-ku, Osaka 541-8564, Japan. 
      Electronic address: y.nanba@ono.co.jp.
FAU - Yamazaki, Naoya
AU  - Yamazaki N
AD  - Department of Dermatologic Oncology, National Cancer Center Hospital, 5-1-1 
      Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. Electronic address: nyamazak@ncc.go.jp.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20181115
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - 0 (B7-H1 Antigen)
RN  - 0 (CD274 protein, human)
RN  - 0 (Ipilimumab)
RN  - 0 (Neoplasm Proteins)
RN  - 31YO63LBSN (Nivolumab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents, Immunological/administration & dosage/adverse 
      effects/pharmacology/*therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - B7-H1 Antigen/antagonists & inhibitors
MH  - Chemical and Drug Induced Liver Injury/etiology
MH  - Drug Synergism
MH  - Endocrine System Diseases/chemically induced
MH  - Female
MH  - Follow-Up Studies
MH  - Gastrointestinal Diseases/chemically induced
MH  - Humans
MH  - Ipilimumab/administration & dosage/adverse effects/pharmacology
MH  - Japan/epidemiology
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Melanoma/*drug therapy/pathology
MH  - Middle Aged
MH  - *Molecular Targeted Therapy/adverse effects
MH  - Neoplasm Proteins/antagonists & inhibitors
MH  - Nivolumab/administration & dosage/adverse effects/pharmacology
MH  - Progression-Free Survival
OTO - NOTNLM
OT  - Acral
OT  - Asian
OT  - Immunotherapy
OT  - Ipilimumab
OT  - Japanese
OT  - Melanoma
OT  - Mucosal
OT  - Nivolumab
OT  - Survival analysis
EDAT- 2018/11/18 06:00
MHDA- 2019/10/08 06:00
CRDT- 2018/11/18 06:00
PHST- 2018/09/19 00:00 [received]
PHST- 2018/09/23 00:00 [accepted]
PHST- 2018/11/18 06:00 [pubmed]
PHST- 2019/10/08 06:00 [medline]
PHST- 2018/11/18 06:00 [entrez]
AID - S0959-8049(18)31395-9 [pii]
AID - 10.1016/j.ejca.2018.09.025 [doi]
PST - ppublish
SO  - Eur J Cancer. 2018 Dec;105:114-126. doi: 10.1016/j.ejca.2018.09.025. Epub 2018 
      Nov 15.