PMID- 28283736
OWN - NLM
STAT- MEDLINE
DCOM- 20170613
LR  - 20231213
IS  - 1432-0843 (Electronic)
IS  - 0344-5704 (Print)
IS  - 0344-5704 (Linking)
VI  - 79
IP  - 4
DP  - 2017 Apr
TI  - Phase 1b study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in 
      Japanese patients with advanced melanoma (KEYNOTE-041).
PG  - 651-660
LID - 10.1007/s00280-016-3237-x [doi]
AB  - PURPOSE: This phase I b study evaluated the safety and anti-tumor activity of 
      pembrolizumab in Japanese patients with advanced melanoma. METHODS: Pembrolizumab 
      (2 mg/kg) was given every 3 weeks (Q3W) for up to 2 years or until confirmed 
      progression or unacceptable toxicity. The tumor response was assessed as per the 
      Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by both 
      investigator review and central review. RESULTS: Forty-two patients with advanced 
      melanoma received pembrolizumab. A primary cutaneous histology was observed in 34 
      patients (81.0%), while a primary mucosal histology was observed in 8 patients 
      (19.0%). Thirty-four patients (81.0%) experienced treatment-related adverse 
      events (AEs). The most common treatment-related AEs were pruritus, maculopapular 
      rash, malaise, and hypothyroidism. Grade 3-5 treatment-related AEs occurred in 8 
      patients (19.0%). The only grade 3-5 treatment-related AE reported in at least 
      two patients was anemia. There were two treatment-related deaths (unknown cause 
      and cerebral hemorrhage). Among the 37 evaluable patients, the confirmed overall 
      response rates (ORRs) determined by central review were 24.1% (95% CI 10.3-43.5) 
      for cutaneous melanoma and 25.0% (95% CI 3.2-65.1) for mucosal melanoma. The 
      responses were durable, and the median duration of response was not reached in 
      either population. The median overall survival (OS) was not reached, with a 
      12-month OS of 82.7% for cutaneous melanoma and 51.4% for mucosal melanoma. 
      CONCLUSION: The safety profile of pembrolizumab in Japanese patients was similar 
      to that reported in the previous clinical studies. Pembrolizumab provided 
      promising anti-tumor activity in Japanese patients with advanced melanoma.
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. nyamazaki@ncc.go.jp.
FAU - Takenouchi, Tatsuya
AU  - Takenouchi T
AD  - Department of Dermatology, Niigata Cancer Center Hospital, Niigata, Japan.
FAU - Fujimoto, Manabu
AU  - Fujimoto M
AD  - Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, 
      Japan.
FAU - Ihn, Hironobu
AU  - Ihn H
AD  - Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto 
      University, Kumamoto, Japan.
FAU - Uchi, Hiroshi
AU  - Uchi H
AD  - Department of Dermatology, Kyushu University School of Medicine, Fukuoka, Japan.
FAU - Inozume, Takashi
AU  - Inozume T
AD  - Department of Dermatology, Faculty of Medicine, University of Yamanashi, 
      Yamanashi, Japan.
FAU - Kiyohara, Yoshio
AU  - Kiyohara Y
AD  - Department of Dermatology, Shizuoka Cancer Center, Shizuoka, Japan.
FAU - Uhara, Hisashi
AU  - Uhara H
AD  - Department of Dermatology, Sapporo Medical University School of Medicine, 
      Sapporo, Japan.
FAU - Nakagawa, Kazuhiko
AU  - Nakagawa K
AD  - Department of Medical Oncology, Kindai University Faculty of Medicine, 
      Osaka-sayama, Japan.
FAU - Furukawa, Hiroshi
AU  - Furukawa H
AD  - Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, 
      Hokkaido University, Sapporo, Japan.
FAU - Wada, Hidefumi
AU  - Wada H
AD  - Department of Dermatology, Yokohama City University School of Medicine, Yokohama, 
      Japan.
FAU - Noguchi, Kazuo
AU  - Noguchi K
AD  - MSD K.K., Tokyo, Japan.
FAU - Shimamoto, Takashi
AU  - Shimamoto T
AD  - MSD K.K., Tokyo, Japan.
FAU - Yokota, Kenji
AU  - Yokota K
AD  - Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, 
      Japan.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
DEP - 20170311
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (PDCD1 protein, human)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - DPT0O3T46P (pembrolizumab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal/adverse effects/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized/adverse effects/*therapeutic use
MH  - Antineoplastic Agents/adverse effects/*therapeutic use
MH  - Asian People
MH  - Disease-Free Survival
MH  - Female
MH  - Humans
MH  - Male
MH  - Melanoma/*drug therapy/genetics/pathology
MH  - Middle Aged
MH  - Programmed Cell Death 1 Receptor/*antagonists & inhibitors/*immunology
MH  - Skin/pathology
MH  - Skin Neoplasms/*drug therapy/genetics/pathology
MH  - Survival Analysis
MH  - Melanoma, Cutaneous Malignant
PMC - PMC5364262
OTO - NOTNLM
OT  - Anti-PD-1 therapy
OT  - Immunotherapy
OT  - Japanese patients
OT  - Melanoma
OT  - Pembrolizumab
COIS- FUNDING: This study was funded by MSD K.K. (Tokyo, Japan). CONFLICT OF INTEREST: 
      K. Nakagawa received a speaker honoraria from Astellas, AstraZeneca, EPS 
      Holdings, Ono Pharmaceutical, Kyowa Hakko Kirin, Showa Yakuhin Kako, SymBio 
      Pharmaceuticals, Daiichi Sankyo, Chugai Pharmaceutical, Nippon Boehringer 
      Ingelheim, Eli Lilly Japan, Pfizer Japan, and Bristol-Myers Squibb, and received 
      research grants funding from Chugai Pharmaceutical, MSD, Ono Pharmaceutical, EPS 
      Associates, Quintiles, Daiichi Sankyo, Japan Clinical Research Operations, Eisai, 
      PPD-SNBL, Pfizer Japan, Takeda Pharmaceutical, Nippon Boehringer Ingelheim, Taiho 
      Pharmaceutical, and Bristol-Myers Squibb. H. Uhara received a speaker honorarium 
      from MSD, Ono Pharmaceutical, Bristol-Myers Squibb, Chugai Pharmaceutical, 
      Novartis Pharma, Roche Diagnostics, and Mochida Pharmaceutical, and received 
      research grants from Ono Pharmaceutical, Chugai Pharmaceutical, and Mochida 
      Pharmaceutical. T. Takenouchi received a speaker honorarium from MSD, Ono 
      Pharmaceutical, and Bristol-Myers Squibb, Chugai Pharmaceutical, and Novartis 
      Pharma. Y. Kiyohara received research grants from Ono Pharmaceutical, Chugai 
      Pharmaceutical, Bristol-Myers Squibb, MSD, Merck Serono, GlaxoSmithKline, and 
      received a speaker honorarium from Ono Pharmaceutical, and Chugai Pharmaceutical, 
      and reported the safety review committee role of Ono Pharmaceutical, and Chugai 
      Pharmaceutical. T. Shimamoto and K. Noguchi are employees of MSD K.K. and hold 
      stock in Merck & Co., Inc., Kenilworth, NJ, USA. N. Yamazaki, M. Fujimoto, H. 
      Ihn, H. Uchi, T. Inozume, H. Furukawa, H. Wada, and K. Yokota declare that they 
      have no conflict of interest. ETHICAL STANDARDS: The study was performed in 
      accordance with the ethical standards established in the 1964 Declaration of 
      Helsinki and its later amendments. The study was approved by the institutional 
      review board of each study site, and all the patients provided informed consent 
      prior to their inclusion in the study.
EDAT- 2017/03/12 06:00
MHDA- 2017/06/14 06:00
PMCR- 2017/03/11
CRDT- 2017/03/12 06:00
PHST- 2016/12/02 00:00 [received]
PHST- 2016/12/28 00:00 [accepted]
PHST- 2017/03/12 06:00 [pubmed]
PHST- 2017/06/14 06:00 [medline]
PHST- 2017/03/12 06:00 [entrez]
PHST- 2017/03/11 00:00 [pmc-release]
AID - 10.1007/s00280-016-3237-x [pii]
AID - 3237 [pii]
AID - 10.1007/s00280-016-3237-x [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2017 Apr;79(4):651-660. doi: 
      10.1007/s00280-016-3237-x. Epub 2017 Mar 11.