Efficacy and safety of nivolumab in Japanese patients with previously untreated advanced melanoma: A phase II study.
Treating advanced or recurrent melanoma remains a challenge. Cancer cells can evade the immune system by blocking T-cell activation through overexpression of the inhibitory receptor programmed death 1 (PD-1) ligands. The PD-1 inhibitor nivolumab blocks the inhibitory signal in T cells, thus overcoming the immune resistance of cancer cells. Nivolumab has shown promising anticancer activity in various cancers. We carried out a single-arm, open-label, multicenter, phase II study to investigate the efficacy and safety of nivolumab in previously untreated Japanese patients with advanced melanoma. Twenty-four patients with stage III/IV or recurrent melanoma were enrolled and received i.v. nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was overall response rate evaluated by an independent radiology review committee. The independent radiology review committee-assessed overall response rate was 34.8% (90% confidence interval, 20.8-51.9), and the overall survival rate at 18 months was 56.5% (90% confidence interval, 38.0-71.4). Treatment-related adverse events (AEs) of grade 3 or 4 only occurred in three patients (12.5%). Two patients discontinued nivolumab because of AEs, but all AEs were considered manageable by early diagnosis and appropriate treatment. Subgroup analyses showed that nivolumab was clinically beneficial and tolerable regardless of BRAF genotype, and that patients with treatment-related select AEs and with vitiligo showed tendency for better survival. In conclusion, nivolumab showed favorable efficacy and safety profiles in Japanese patients with advanced or recurrent melanoma, with or without BRAF mutations. (Trial registration no. JapicCTI-142533.).
Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan.
Naoya
http://orcid.org/0000-0002-9638-0428
N
Yamazaki
Dermatology Division, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
Yoshio
Y
Kiyohara
Department of Dermatology, Shinshu University School of Medicine, Nagano, Japan.
Hisashi
H
Uhara
Department of Dermatology, Asahikawa Medical University, Hokkaido, Japan.
Jiro
J
Uehara
Department of Dermatology, University of Tsukuba Hospital, Ibaraki, Japan.
Manabu
M
Fujimoto
Department of Dermatology, Niigata Cancer Center Hospital, Niigata, Japan.
Tatsuya
T
Takenouchi
Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Masaki
M
Otsuka
Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Hiroshi
H
Uchi
Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Hironobu
H
Ihn
Department Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Hyogo, Japan.
Hironobu
H
Minami
D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D044466:Asian People; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism; D000077594:Nivolumab; D048493:Proto-Oncogene Proteins B-raf / Q000378:metabolism; D015996:Survival Rate
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000077594:Nivolumab; D048493:Proto-Oncogene Proteins B-raf
Immune checkpoint inhibitor; Japanese patients; melanoma; nivolumab; programmed death 1 (PD-1) inhibitor