Association Between Cutaneous Immune-Related Adverse Events and Efficacy of Immune Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer

<b>Background/Objectives</b>: Immune checkpoint inhibitors (ICIs) have transformed the treatment of patients with non-small cell lung cancer (NSCLC). Numerous studies have suggested that immune-related adverse events (irAEs) are associated with ICI efficacy and can affect any organ system. This study aims to evaluate the prognostic significance of cutaneous IrAEs (cirAEs) and their impact on the effectiveness of PD-1/PD-L1 inhibitors in real-world NSCLC data. <b>Methods</b>: We retrospectively collected NSCLC patients treated with ICI as first- or second-line therapy between 2015 and 2022 at a single institution. We evaluated the association between cirAEs and treatment efficacy, measured by objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Kaplan-Meier survival curves were generated, and log-rank tests were used for significance testing. Multivariable analysis was performed using Cox proportional hazards regression models. <b>Results</b>: A total of 510 patients were included in the analysis, with a median age of 62 years (range 34-85), and 75% of patients were males. CirAEs of any grade were observed in 139 patients (27.3%). Among patients assessed for efficacy, the ORR was significantly higher in those with cirAEs compared to those without (54.3% vs. 29.9%, <i>p</i> = 0.0001). At a median follow-up of 48 months, PFS (14.6 vs. 4.7 months, <i>p</i> = 0.0001) and OS (29 vs. 9.2 months, <i>p</i> = 0.0001) were significantly improved in patients with cirAEs. Patients with grade 1-2 cirAEs showed even greater survival benefits (PFS: median 14.9 months, <i>p</i> = 0.003; OS: median 30 months, <i>p</i> = 0.001). Multivariable analysis confirmed that the development of any cirAE was independently associated with significantly improved OS (hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.44-0.80, <i>p</i> = 0.0001). The presence of multisystem ≥ 2 SOC irAEs, including cirAE, was strongly correlated with the greatest benefit from ICIs HR:0.51 (95% CI 0.35-0.74), <i>p</i> = 0.001. <b>Conclusions</b>: This study supports that cirAEs could be used as a potential marker of ICI efficacy in NSCLC. The development of multisystem cirAEs may prognose the greatest benefit of treatment.