Immune-related adverse events as prognostic biomarkers in recurrent or metastatic nasopharyngeal carcinoma receiving PD-L1 inhibitor: A post-hoc analysis of the multicenter, single-arm, phase 2 study.

BACKGROUND: Immune-related adverse events (irAEs) have been associated with better therapeutic outcomes in patients receiving immune checkpoint inhibitors (ICIs) across various cancers. This study investigates the association between irAEs and ICI outcomes in patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC). METHODS: A post hoc analysis was performed on 153 patients with R/M NPC who received anti-PD-L1 inhibitors between February 26, 2019, and January 13, 2021. These patients were enrolled in a multicenter, single-arm, phase 2 clinical trial, which represents the largest study to date evaluating anti-PD-L1 therapy in previously treated R/M NPC. RESULTS: Patients who experienced irAEs had significantly higher overall response rates (ORR) and diseade control rates (DCR) compared to those without irAEs (31.2 % vs. 17.1 %, p = 0.039; 66.7 % vs. 44.8 %, p = 0.017). Additionally, the median progression-free survival (PFS) was longer in patients with irAEs (129 days vs. 56 days, p = 0.007). Patients with endocrine-related irAEs exhibited higher DCR (71.8 % vs. 46.2 %, p = 0.012), and longer PFS (144 days vs. 69 days, p = 0.02) and overall survival (OS: 746 days vs. 438 days, p = 0.02). In contrast, patients with grade >/= 3 irAEs or thoserequiring systemic steroid therapy had shorter median OS (179 days vs. 466 days, p = 0.03; 166 days vs. 462 days, p = 0.02). CONCLUSIONS: The occurrence of irAEs, particularly those involving the endocrine system, is associated with enhanced efficacy of anti-PD-L1 therapy and extended survival in patients with R/M NPC, highlighting their potential as prognostic biomarkers.