Effect of renin-angiotensin-aldosterone system inhibitors on survival outcomes in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis

Jinhai Shen; Hui Hou; Bowen Liang; Xiao Guo; Li Chen; Yong Yang; Yun Wang

doi:10.3389/fimmu.2023.1155104

Effect of renin-angiotensin-aldosterone system inhibitors on survival outcomes in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis

Front Immunol. 2023 Apr 19:14:1155104. doi: 10.3389/fimmu.2023.1155104. eCollection 2023.

Authors

Jinhai Shen^{1

2}, Hui Hou^{1

2}, Bowen Liang^{1

2}, Xiao Guo^{1

2}, Li Chen³, Yong Yang^{1

2

4}, Yun Wang^{1

2}

Affiliations

¹ Center for New Drug Safety Evaluation and Research, China Pharmaceutical University, Nanjing, Jiangsu, China.
² State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, China.
³ Department of Pharmacology, Suzhou Institute for Drug Control, Suzhou, Jiangsu, China.
⁴ School of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, China.

Abstract

Background: Effect of renin-angiotensin-aldosterone system inhibitors (RAASIs) in combination with immune checkpoint inhibitors (ICIs) on prognoses in cancer patients remains controversial. This study systematically evaluated the effect of RAASIs on survival outcomes in cancer patients receiving ICIs treatment and provided an evidence-based reference for the rational use of RAASIs and ICIs combination therapy in clinical practice.

Methods: Studies evaluating the prognosis of RAASIs-used versus RAASIs-free in cancer patients receiving ICIs treatment from inception to 1 November 2022 were retrieved by searching PubMed, Cochrane Library, Web of Science, Embase, and major conference proceedings. Studies in English reporting hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and/or progression-free survival (PFS) were included. Statistical analyses were conducted using the software Stata 17.0.

Results: A total of 12 studies containing 11739 patients were included, comprising ~4861 patients in the RAASIs-used and ICIs-treated group and ~6878 patients in RAASIs-free and ICIs-treated group. The pooled HR was 0.85 (95%CI, 0.75-0.96; P = 0.009) for OS and 0.91 (95%CI, 0.76-1.09; P = 0.296) for PFS, indicating a positive effect of RAASIs concomitant with ICIs on cancer patients. This effect was observed especially in patients with urothelial carcinoma (HR, 0.53; 95%CI, 0.31-0.89; P = 0.018) and renal cell carcinoma (HR, 0.56; 95%CI, 0.37-0.84; P = 0.005) on OS.

Conclusion: Concomitant use of RAASIs and ICIs enhanced the efficacy of ICIs and this combination regimen was associated with significantly improved OS and a trend towards better PFS. RAASIs can be considered as adjuvant drugs when hypertensive patients receive ICIs treatment. Our results provide an evidence-based reference for the rational use of the RAASIs and ICIs combination therapy to improve the efficacy of ICIs in clinical practice.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022372636; https://inplasy.com/, identifier INPLASY2022110136.

Keywords: cancer; immune checkpoint inhibitors; meta-analysis; renin-angiotensin-aldosterone system inhibitors; survival.

Publication types

Meta-Analysis
Systematic Review
Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Transitional Cell*
Humans
Immune Checkpoint Inhibitors / therapeutic use
Kidney Neoplasms*
Renin-Angiotensin System
Urinary Bladder Neoplasms*

Substances

Immune Checkpoint Inhibitors

Grants and funding

This work was supported by National Natural Science Foundation of China grants (81673468), Jiangsu Market Supervision Administration Science and Technology Project (KJ21125066).