title: Phase 1b study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced melanoma (KEYNOTE-041).
abstract: This phase I b study evaluated the safety and anti-tumor activity of pembrolizumab in Japanese patients with advanced melanoma.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Dermatologic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. nyamazaki@ncc.go.jp.
authors.forename: Naoya
authors.initials: N
authors.lastname: Yamazaki
authors.affiliation: Department of Dermatology, Niigata Cancer Center Hospital, Niigata, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Takenouchi
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Fujimoto
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Ihn
authors.affiliation: Department of Dermatology, Kyushu University School of Medicine, Fukuoka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uchi
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Inozume
authors.affiliation: Department of Dermatology, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kiyohara
authors.affiliation: Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Uhara
authors.affiliation: Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-sayama, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Furukawa
authors.affiliation: Department of Dermatology, Yokohama City University School of Medicine, Yokohama, Japan.
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Wada
authors.affiliation: MSD K.K., Tokyo, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Noguchi
authors.affiliation: MSD K.K., Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimamoto
authors.affiliation: Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yokota
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000276:immunology*; D012867:Skin / Q000473:pathology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016019:Survival Analysis; D000096142:Cutaneous Malignant Melanoma
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C582435:pembrolizumab
keywords: Anti-PD-1 therapy; Immunotherapy; Japanese patients; Melanoma; Pembrolizumab