Prognostic relevance of immune-related adverse events in lung cancer patients undergoing immune checkpoint inhibitor therapy: a systematic review and meta-analysis

Yuchen Huang; Wananqi Ma; Dongsheng Wu; Mengyuan Lyu; Quan Zheng; Tengyong Wang; Jian Zhou; Chengwu Liu

doi:10.21037/tlcr-24-299

Prognostic relevance of immune-related adverse events in lung cancer patients undergoing immune checkpoint inhibitor therapy: a systematic review and meta-analysis

Transl Lung Cancer Res. 2024 Jul 30;13(7):1559-1584. doi: 10.21037/tlcr-24-299. Epub 2024 Jul 12.

Authors

Yuchen Huang^#¹, Wananqi Ma^#¹, Dongsheng Wu^{1

2}, Mengyuan Lyu³, Quan Zheng^{1

2}, Tengyong Wang^{1

2}, Jian Zhou², Chengwu Liu²

Affiliations

¹ West China School of Medicine, Sichuan University, Chengdu, China.
² Department of Thoracic Surgery and Institute of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, China.
³ Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.

^# Contributed equally.

Abstract

Background: Immune checkpoint inhibitors (ICIs) work by activating the immune system, a mechanism that may also cause immune-related adverse events (irAEs). This study seeks to investigate on how different irAEs impact prognosis of advanced lung cancer (LC) patients and identify useful approaches to manage irAEs.

Methods: A thorough literature search of PubMed, Embase, the Cochrane Library and manual searches up to January 2024 were undertaken. Treatment outcomes including progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR) were obtained. Meta-analysis was conducted using R software (version 4.3.1).

Results: There were 106 studies with 41,050 advanced or recurrent LC patients included. The occurrence of irAEs was correlated with better PFS [hazard ratio (HR) =0.54; 95% confidence interval (CI): 0.49-0.59], OS (HR =0.57; 0.51-0.63), ORR [risk ratio (RR) =2.03; 95% CI: 1.81-2.28] and DCR (RR =1.55; 95% CI: 1.40-1.72) and remained significant after adjusting programmed death-ligand 1 (PD-L1) level. IrAEs affecting skin (OS: HR =0.45; 95% CI: 0.38-0.53) and endocrine system (OS: HR =0.51; 95% CI: 0.41-0.62), of mild severity (OS: HR =0.52; 95% CI: 0.35-0.79), arising in multiple sites (OS: HR =0.47; 95% CI: 0.38-0.59), induced by monotherapy (OS: HR =0.58; 95% CI: 0.52-0.65), with a delayed onset (cutoff: 3 months; OS: HR =0.37; 95% CI: 0.19-0.71) were identified as positive prognostic markers. In contrast, though pulmonary irAEs were found to be corelated with enhanced treatment response (ORR: RR =1.75; 95% CI: 1.37-2.25), they may harm survival, especially those with grade ≥3 (OS: HR =2.40; 95% CI: 1.39-4.14). Treatment resumption tended to improve PFS but might not reduce the risk of death compared to permanent discontinuation.

Conclusions: IrAEs suggest better treatment outcomes generally, yet severe pneumonia could increase mortality risk. Close supervision and appropriate handling protocols are warranted to weigh treatment benefit against risk.

Keywords: Immune-related adverse event (irAE); immune checkpoint inhibitors (ICIs); lung cancer (LC); meta-analysis; prognosis.