Immune-related adverse event-related adrenal insufficiency mediates immune checkpoint inhibitors efficacy for cancer treatment

Abstract

Abstract Purpose Immune checkpoint inhibitors (ICIs) have significantly improved the outcomes of patients with cancer. An increasing number of immune-related adverse events (irAEs) have been discovered with the widespread clinical application of ICIs, which appear to be associated with improved treatment efficacy in certain cancers. We aimed to evaluate the correlation between irAE-related adrenal insufficiency (AI) and ICI treatment efficacy. Methods Patients were divided into irAE-A (patients with irAE-related AI), irAE-B (patients with other irAEs) and non-irAE groups. Immunotherapy efficacy was assessed based on the disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Survival probabilities were estimated using the Kaplan–Meier method with the log–rank test. Results One hundred and ninety-two patients with cancer including gastrointestinal, respiratory, and other cancers, who received ICIs were enrolled in this study. The DCR of the irAE-A and irAE-B groups were higher than that of the non-irAE group (P < 0.05). Multiple extended Cox regression analyses showed that irAE status (irAE-A vs. non-irAE, P = 0.008; irAE-B vs. non-irAE, P = 0.020), ECOG status (P = 0.045), TNM stage (P = 0.000), and treatment line (P = 0.002) were independent predictors of PFS. Meanwhile, irAE status (irAE-A vs. non-irAE, P = 0.009; irAE-B vs. non-irAE, P = 0.013), ECOG status (P = 0.007), TNM stage (P = 0.035), treatment line (P = 0.001) and treatment modality (P = 0.008) were independent predictors for OS. Conclusions IrAE-related AI was significantly associated with better clinical outcomes in patients with cancer and is a potentially predictable marker for better ICI treatment efficacy.