Open AccessEfficacy and safety of nivolumab in Japanese patients with previously untreated advanced melanoma: A phase II study
Author(s) -
Yamazaki Naoya,
Kiyohara Yoshio,
Uhara Hisashi,
Uehara Jiro,
Fujimoto Manabu,
Takenouchi Tatsuya,
Otsuka Masaki,
Uchi Hiroshi,
Ihn Hironobu,
Minami Hironobu
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13241
Subject(s) - nivolumab , medicine , melanoma , adverse effect , clinical endpoint , oncology , confidence interval , response evaluation criteria in solid tumors , phases of clinical research , progressive disease , vitiligo , cancer , toxicity , gastroenterology , surgery , immunotherapy , disease , immunology , cancer research , clinical trial
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 ( AE s) of grade 3 or 4 only occurred in three patients (12.5%). Two patients discontinued nivolumab because of AE s, but all AE s 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 AE s 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. Japic CTI ‐142533.)