We aimed to investigate clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab plus ipilimumab (Nivo/Ipi) who either resumed or permanently discontinued treatment following immune-related adverse events (irAEs) that necessitated treatment interruption.
A database of 129 metastatic renal cell carcinoma (mRCC) patients treated with Nivo/Ipi at 6 Japanese institutions was analyzed, dividing the patients into 3 groups: those without treatment interruption ("no interruption"), those who resumed treatment after irAEs ("retreatment"), and those who permanently discontinued treatment after irAEs ("discontinuation").
The no interruption, retreatment, and discontinuation group included 58, 35, and 36 patients, respectively. Median time to initial irAE requiring treatment interruption was comparable between the retreatment and discontinuation groups (2.1 vs. 2.6 months, P = 0.53). Although the type and severity of initial irAEs leading to interruption were evenly distributed between the retreatment and discontinuation groups, high-dose glucocorticoids were required less frequently in the retreatment group (7 vs. 16 patients, P = 0.033). Among the 35 patients in the retreatment group, 5 developed new irAEs and 2 experienced recurrences of previous irAEs, with grade 3/4 irAEs occurring in 3 patients. Objective response rates to Nivo/Ipi were 30%, 63%, and 64% in the no interruption, retreatment, and discontinuation groups, respectively. Progression-free survival (PFS) and overall survival (OS) were comparable between the retreatment and discontinuation groups (median PFS: 28.5 vs. 26.0 months, P = 0.60; 3-year OS: 69% vs. 78%, P = 0.70), whereas both were significantly shorter in the no interruption group (median PFS: 4.1 months; 3-year OS: 28%).
Although resuming Nivo after irAEs requiring treatment interruption appears to be safe in carefully selected patients, permanent discontinuation also offers favorable oncological outcomes, indicating it may be a viable alternative.
Urologic oncology. 2025 Nov 18 [Epub ahead of print]
Yuta Sano, Masaharu Inoue, Satoshi Washino, Suguru Shirotake, Hideki Takeshita, Yuji Miura, Akinari Nakayama, Shoichi Nagamoto, Tomoaki Miyagawa, Masafumi Oyama, Satoru Kawakami, Kazutaka Saito, Yoh Matsuoka
Department of Urology, Saitama Cancer Center, Saitama, Japan., Department of Urology, Saitama Cancer Center, Saitama, Japan; Department of Genitourinary Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan; Musashino Study Group, Saitama, Japan. Electronic address: ., Department of Urology, Jichi Medical University Saitama Medical Center, Omiya-ku, Saitama, Japan; Musashino Study Group, Saitama, Japan., Department of Uro-Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan; Musashino Study Group, Saitama, Japan., Department of Urology, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan; Musashino Study Group, Saitama, Japan., Department of Medical Oncology, Toranomon Hospital, Minato-ku, Tokyo, Japan; Department of Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan; Musashino Study Group, Saitama, Japan., Department of Urology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Saitama, Japan; Musashino Study Group, Saitama, Japan., Department of Urology, Jichi Medical University Saitama Medical Center, Omiya-ku, Saitama, Japan., Department of Uro-Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan., Department of Urology, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan., Department of Urology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Saitama, Japan.