Thyroid dysfunction induced by anti-PD-1 therapy is associated with a better progression-free survival in patients with advanced carcinoma

Abstract

Abstract Purpose Immune checkpoint inhibitors are associated with immune-related adverse events. Thyroid dysfunction during anti-programmed cell death 1(anti-PD-1) therapy remains to be fully characterized and mechanism underlying this complication and effects on patient prognosis remain unclear. Methods Patients with advanced carcinoma treated with anti-PD-1 therapy were evaluated for thyroid function at baseline and after treatment initiation from August 2020 to March 2022. Seventy-three patients were finally included in the study. Results Among these patients, 19 (26.03%) developed thyroid dysfunction after receiving anti-PD-1 therapy. Primary hypothyroidism and thyrotoxicosis were the most common clinical manifestation. Anti-PD-1 induced thyroid dysfunction occurred 63 (26-131) days after administration, thyrotoxicosis appeared earlier than primary hypothyroidism. In Kaplan–Meier survival analysis, the progression-free survival (PFS) of the thyroid dysfunction group was better than that of the non-thyroid dysfunction group (227 (95% confidence interval (CI): 50.85-403.15) days vs 164 (95% CI: 77.76-250.24) days, p=0.026). Male patients had better PFS than female patients (213 (95% CI: 157.74-268.26) days vs 74 (95% CI: 41.23-106.77) days, p=0.031). In cox proportional hazards regression model, anti-PD-1 induced thyroid dysfunction remained an independent predictor of better PFS (Hazard ratio (HR)=0.339(0.136-0.848), p=0.021). Conclusion Thyroid dysfunction is a common immune-related adverse events in advanced cancer patients treated with anti-PD-1 therapy and predicts a better prognosis. This study was retrospectively registered with Trial ClinicalTrials.gov (NCT05593744) on October 25, 2022.