イシハラ　ヒロキ   Ishihara Hiroki   石原　弘喜    所属   医学部 医学科（東京女子医科大学病院）    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Association between immune-related adverse events and prognosis in patients with metastatic renal cell carcinoma treated with nivolumab.
掲載誌名	正式名：Urologic oncology 略　 称：Urol Oncol ISSNコード：18732496/10781439
掲載区分	国外
巻・号・頁	37(6),pp.355.e21-355.e29
著者・共著者	ISHIHARA Hiroki†*, TAKAGI Toshio, KONDO Tsunenori, MUROMIYA Chie, TACHIBANA Hidekazu, FUKUDA Hironori, YOSHIDA Kazuhiko, IIZUKA Junpei, KOBAYASHI Hirohito, OKUMI Masayoshi, ISHIDA Hideki, TANABE Kazunari
担当区分	筆頭著者,責任著者
発行年月	2019/06
概要	OBJECTIVES:Immune-related adverse events (irAEs) develop in a subset of patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors. The relationship between presence of irAEs and prognosis in these patients remains unknown. Thus, we evaluated the prognostic impact of irAEs caused by nivolumab therapy in mRCC patients who had received prior molecular-targeted therapies.METHODS:We retrospectively evaluated 47 patients with mRCC who were treated with nivolumab after receiving at least 1 molecular-targeted therapy. The irAEs assessed in this study included cutaneous, gastrointestinal, endocrine, pulmonary, hepatobiliary, renal, and other (rheumatic disease and pancreatitis) manifestations. The grade of irAEs was defined based on the Common Terminology Criteria for Adverse Events version 4.0.RESULTS:In total, 23/47 patients (48.9%) experienced 29 irAEs. The most frequent irAE was rash/pruritus (12/23, 52.2%). The median progression-free survival (PFS) and overall survival after the initiation of nivolumab therapy were significantly longer in patients with irAEs than in those without irAEs (PFS: 13.1 vs. 4.87 months, P < 0.0001; overall survival: 26.0 vs. not reached, P = 0.0072). The multivariate analysis of PFS showed that irAE development was an independent prognostic factor (hazard ratio: 0.25, P = 0.0009). Additionally, the 2-cycle landmark analysis showed that PFS was significantly longer in patients with irAEs than in those without irAEs (median: not reached vs. 6.28 months, P = 0.0279).CONCLUSIONS:This retrospective study revealed a significant association between nivolumab-associated irAEs and prognosis in previously treated mRCC. Further prospective studies are necessary to confirm our findings.
DOI	10.1016/j.urolonc.2019.03.003
PMID	30935847