The incidence of immune-related adverse events (irAEs) and their association with clinical outcomes in advanced renal cell carcinoma and urothelial carcinoma patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis

Yaowen Zhang; Junru Chen; Haoyang Liu; Jindong Dai; Junjie Zhao; Sha Zhu; Xingming Zhang; Jiayu Liang; Xu Hu; Jinge Zhao; Zhenhua Liu; Pengfei Shen; Guangxi Sun; Hao Zeng

doi:10.1016/j.ctrv.2024.102787

The incidence of immune-related adverse events (irAEs) and their association with clinical outcomes in advanced renal cell carcinoma and urothelial carcinoma patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis

Cancer Treat Rev. 2024 Jun 15:129:102787. doi: 10.1016/j.ctrv.2024.102787. Online ahead of print.

Authors

Yaowen Zhang¹, Junru Chen¹, Haoyang Liu¹, Jindong Dai¹, Junjie Zhao¹, Sha Zhu², Xingming Zhang¹, Jiayu Liang¹, Xu Hu¹, Jinge Zhao¹, Zhenhua Liu¹, Pengfei Shen¹, Guangxi Sun³, Hao Zeng⁴

Affiliations

¹ Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, China.
² Department of Urology, University of California, San Francisco, 94158, CA, USA.
³ Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: sungx077@126.com.
⁴ Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: kucaizeng@163.com.

PMID: 38905806
DOI: 10.1016/j.ctrv.2024.102787

Abstract

Background: This study aimed to summarize the occurrence of immune-related adverse events (irAEs) and further evaluate their association with clinical outcomes in patients with advanced renal cell carcinoma (RCC) and urothelial carcinoma (UC) treated with immune checkpoint inhibitors (ICIs).

Methods: A comprehensive search of PubMed, Embase, and the Cochrane Library up to December 2023 was conducted to identify eligible studies. The details of irAEs and data regarding their correlation with clinical outcomes were extracted. R software was used for meta-analysis.

Results: A total of 27 studies involving 6148 patients with RCC or UC were included. The pooled overall incidence for any-grade and grade ≥ 3 irAEs was 44.2 % (95 % CI: 38.1 %-50.5 %) and 15.7 % (95 % CI: 11.4 %-21.1 %), respectively. Compared to those without any irAEs, patients with irAEs showed improved PFS (HR = 0.44, 95 % CI: 0.35-0.56, p < 0.01) and OS (HR = 0.47, 95 % CI: 0.42-0.51, p < 0.01), as well as higher ORR (OR = 3.59, 95 % CI: 3.01-4.29, p < 0.01) and DCR (OR = 4.23, 95 % CI: 3.06-5.84, p < 0.01). Subgroup analysis indicated that clinical outcome improvements were associated with the occurrence of irAEs, regardless of tumor type or ICI agent. Notably, patients with cutaneous irAEs, thyroid dysfunction, and grade ≤ 2 irAEs had a higher probability to achieve better survival benefits from ICI-based therapy, while pulmonary irAEs and grade ≥ 3 irAEs seemed to have a negative impact on OS. Additionally, systemic glucocorticoids administration did not affect survival outcomes.

Conclusion: Our findings suggest that the occurrence of irAEs could be considered as a potential prognostic factor for predicting the efficacy of ICIs in patients with advanced RCC and UC.

Keywords: Clinical outcomes; Immune checkpoint inhibitors; Immune-related adverse events; Renal cell carcinoma; Urothelial carcinoma.

Publication types

Review