Impact of Immune-Related Adverse Event Frequency, Severity and Corticosteroid Use on Immune Checkpoint Inhibitor Efficacy in Non-Small Cell Lung Cancer

Background/Objectives: Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape of non-small cell lung cancer (NSCLC), introducing a distinct spectrum of immune-related toxicities (irAEs). However, the real-world impact of irAEs and corticosteroid use on treatment outcomes remains uncertain. Methods: We conducted a multicenter, retrospective study including patients with advanced NSCLC treated with ICIs alone or in combination with chemotherapy between April 2017 and December 2023. Clinical records were reviewed to collect data on irAEs and corticosteroid administration. Efficacy and safety outcomes were compared according to irAE occurrence, grade, and corticosteroid use. Categorical variables were analyzed using chi-square tests, while PFS and OS were estimated using the Kaplan–Meier method and compared with the log-rank test. Cox proportional hazards models were used to estimate HRs and 95% CIs. Results: Among 452 patients, 151 (33.4%) experienced irAEs of any grade, and 37 (8.2%) developed grade ≥3 events. The most common irAEs were dermatologic (11.1%), endocrine disorders (9.1%), and arthritis (5.5%). Corticosteroids were administered for irAE management in 60 patients (13.3%). Patients who developed irAEs achieved significantly improved progression-free survival (median PFS: 23.2 vs. 4.2 months; HR = 0.29; p < 0.001) and overall survival (median OS: 31.2 vs. 7.6 months; HR = 0.35; p < 0.001), including those with grade ≥3 events. The survival benefit associated with irAEs was not compromised by corticosteroid (CS) use for irAE management (median PFS 46.3 in irAE vs. 5.5 months in non-irAE/no use; HR = 0.28; p < 0.001). Temporary ICI discontinuation due to irAEs was associated with longer median PFS (39.1 vs. 5.6 months; HR = 0.29; p < 0.001), as was permanent ICI discontinuation due to irAEs (median not reached vs. 7.4 months; HR = 0.20; p < 0.001). Conclusions: In this retrospective cohort, the occurrence of irAEs—and their management with CS—was associated with enhanced ICI efficacy in metastatic NSCLC, including among patients who developed high-grade toxicities and those who discontinued treatment due to toxicity.