Prognostic impact of immune-related adverse events in recurrent or metastatic sinonasal squamous cell carcinoma treated with immune checkpoint inhibitors.

PURPOSE: In sinonasal squamous cell carcinoma (SNSCC), evidence regarding the efficacy of immune checkpoint inhibitors (ICIs) and predictive biomarkers remains limited. Immune-related adverse events (irAEs) have been reported as potential indicators of antitumor response and clinical benefit in multiple malignancies; however, their prognostic significance in SNSCC has not been well defined.

METHODS

We retrospectively analyzed 37 patients with recurrent or metastatic (R/M) SNSCC who received ICIs at two institutions. Clinical outcomes, including objective response rate (ORR), overall survival (OS), and progression-free survival (PFS), were assessed. The association between irAE occurrence and OS was evaluated using both landmark analysis and time-dependent Cox proportional hazards models treating irAE occurrence as a time-varying covariate.

RESULTS

Among the 37 patients, the ORR was 40.5%, with a median OS of 32.1 months and median PFS of 6.6 months. Twenty-one patients (56.8%) experienced a total of 25 irAEs. In the 3-month landmark analysis, patients with irAEs had significantly better OS and PFS (P = 0.0009 and 0.0008, respectively). However, in the time-dependent Cox model, irAE occurrence was not significantly associated with OS (hazard ratio 0.98, 95% confidence interval 0.38-2.54, P = 0.9627), likely reflecting the influence of late-onset events and the small cohort size.

CONCLUSIONS

Although irAEs were associated with improved survival in landmark analysis, this association was not confirmed in time-dependent analysis, suggesting a potential influence of immortal time bias. Further prospective studies are warranted.