Immune-Related Adverse Events Predict the Efficacy of Immune Checkpoint Inhibitors in Lung Cancer Patients: A Meta-Analysis.

Donghui Wang,Yong Song,Cen Chen,Yanli Gu,Wanjun Lu,Tangfeng Lv,Fang Zhang,Ping Zhan,Hongbing Liu

doi:10.3389/fonc.2021.631949

Abstract

BackgroundImmune-related adverse events (irAEs) have been reported to be associated with the efficacy of immunotherapy. Herein, we conducted a meta-analysis to demonstrate that irAEs could predict the efficacy of immune checkpoint inhibitors (ICIs) in lung cancer patients.MethodsLiterature on the correlation between irAEs and the efficacy of immunotherapy in lung cancer patients were searched to collect the data on objective response rate (ORR), overall survival (OS), or progression-free survival (PFS) of the patients. These data were incorporated into the meta-analysis.ResultsA total of 34 records encompassing 8,115 patients were examined in this study. The irAEs occurrence was significantly associated with higher ORR {risk ratio (RR): 2.43, 95% confidence interval (CI) [2.06–2.88], p < 0.00001} and improved OS {hazard ratio (HR): 0.51, 95% CI [0.43–0.61], p < 0.00001}, and PFS (HR: 0.50, 95% CI [0.44–0.57], p < 0.00001) in lung cancer patients undergoing ICIs. Subgroup analysis revealed that OS was significantly longer in patients who developed dermatological (OS: HR: 0.53, 95%CI [0.42–0.65], p < 0.00001), endocrine (OS: HR: 0.55, 95%CI [0.45–0.67], p < 0.00001), and gastrointestinal irAEs (OS: HR: 0.58, 95%CI [0.42–0.80], p = 0.0009) than in those who did not. However, hepatobiliary, pulmonary, and high-grade (≥3) irAEs were not correlated with increased OS and PFS.ConclusionThe occurrence of irAEs in lung cancer patients, particularly dermatological, endocrine, and gastrointestinal irAEs, is a predictor of enhanced ICIs efficacy.

Highlights

Immunotherapy has led to unprecedented improvements in the life expectancy of cancer patients, those with lung cancer, by priming the immune system to fight against the tumor cells
The Immune-related adverse events (irAEs) occurrence was significantly associated with higher objective response rate (ORR) {risk ratio (RR): 2.43, 95% confidence interval (CI) [2.06–2.88], p < 0.00001} and improved overall survival (OS) {hazard ratio (HR): 0.51, 95% CI [0.43–0.61], p < 0.00001}, and progression-free survival (PFS) (HR: 0.50, 95% CI [0.44–0.57], p < 0.00001) in lung cancer patients undergoing immune checkpoint inhibitors (ICIs)
Subgroup analysis revealed that OS was significantly longer in patients who developed dermatological (OS: HR: 0.53, 95%CI [0.42–0.65], p < 0.00001), endocrine (OS: HR: 0.55, 95%CI [0.45–0.67], p < 0.00001), and gastrointestinal irAEs (OS: HR: 0.58, 95%CI [0.42–0.80], p = 0.0009) than in those who did not

Summary

Introduction

Immunotherapy has led to unprecedented improvements in the life expectancy of cancer patients, those with lung cancer, by priming the immune system to fight against the tumor cells. ICIs target cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1), which are critical molecules that negatively regulate the T-cell activity and aid the tumor cells in evading immune surveillance. The underlying mechanism has not been completely elucidated, increased T-cell activity, B-cellmediated autoantibody production, and cross-reactive tumoral antigenicity have been suggested to be involved in the occurrence of irAEs [2]. Immune-related adverse events (irAEs) have been reported to be associated with the efficacy of immunotherapy. We conducted a meta-analysis to demonstrate that irAEs could predict the efficacy of immune checkpoint inhibitors (ICIs) in lung cancer patients

Methods

Results

Conclusion