KOBAYASHI Hirohito    Department   School of Medicine(Tokyo Women's Medical University Adachi Medical Center), School of Medicine    Position   Associate Professor
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Prognostic impact of early treatment interruption of nivolumab plus ipilimumab due to immune-related adverse events as first-line therapy for metastatic renal cell carcinoma: A multi-institution retrospective study.
Journal	Formal name：Targeted oncology. ISSN code：17762596/1776260X
Domestic / Foregin	Foregin
Volume, Issue, Page	16(4),pp.493-502
Author and coauthor	ISHIHARA Hiroki†, NEMOTO Yuki, NAKAMURA Kazutaka, IKEDA Takashi, TACHIBANA Hidekazu, FUKUDA Hironori, YOSHIDA Kazuhiko, KOBAYASHI Hirohito, IIZUKA Junpei, SHIMMURA Hiroaki, HASHIMOTO Yasunobu, TAKAGI Toshio, ISHIDA Hideki, KONDO Tsunenori, TANABE Kazunari
Publication date	2021/07
Summary	BACKGROUND:It remains unclear how early treatment interruption of nivolumab plus ipilimumab due to immune-related adverse events affects the outcome of previously untreated metastatic renal cell carcinoma (mRCC).OBJECTIVE:To investigate the prognostic impact of the early interruption of nivolumab plus ipilimumab, used as first-line therapy for mRCC.PATIENTS AND METHODS:We retrospectively evaluated 59 intermediate- or poor-risk mRCC patients who received nivolumab plus ipilimumab as first-line therapy. Based on whether early treatment interruption was implemented within the initial four treatment cycles (i.e., 3 months) or not, progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were compared. The prognostic association was further compared with that of 186 patients treated with tyrosine kinase inhibitors (TKIs) as first-line therapy.RESULTS:Twenty-three of the 59 patients (39%) experienced interruption of nivolumab plus ipilimumab therapy. The patients with interruption had longer PFS (p = 0.0055), similar OS (p = 0.366), and likely higher ORR (p = 0.0660) than those without interruption. Of the patients treated with TKIs, 60 of 186 (32%) experienced interruption, with shorter PFS (p = 0.0121), similar OS (p = 0.378), and similar ORR (p = 0.738) than those without interruption. In the 23 patients with nivolumab plus ipilimumab interruption, high-dose corticosteroids were administered in seven patients (30%). PFS (p = 0.638), OS (p = 0.968), or ORR (p = 0.760) did not differ based on corticosteroid administration.CONCLUSIONS:Early treatment interruption, which exerted a negative effect for TKIs, was a preferable event for nivolumab plus ipilimumab when considering PFS. Furthermore, early administration of high-dose corticosteroids did not diminish the anti-tumor effect of nivolumab plus ipilimumab.
DOI	10.1007/s11523-021-00825-2
PMID	34173936