Association of basal thyroid function with clinical outcomes in patients with recurrent or metastatic nasopharyngeal carcinoma treated with PD-L1 inhibitor KL-A167: a multicenter post hoc analysis.

Abstract

Objective: While thyroid dysfunction during PD-L1 inhibitor therapy correlates with efficacy in recurrent/metastatic nasopharyngeal carcinoma, the prognostic value of basal thyroid function remains unclear. This study investigated the relationship between baseline serum thyroid-stimulating hormone (TSH) and clinical outcomes.

Methods: We conducted a multicenter, retrospective analysis of 153 recurrent/metastatic nasopharyngeal carcinoma (R/M NPC) patients from a prospective phase 2 trial of the PD-L1 inhibitor KL-A167. Patients were stratified by baseline TSH levels. Multivariate Cox and logistic regression models were used to analyze progression-free survival (PFS), overall survival (OS), and objective response rate (ORR).

Results: High basal TSH (n = 58) was independently associated with significantly prolonged OS (HR 0.56, 95% CI: 0.36-0.88; P = 0.011) and PFS (HR 0.60, 95% CI: 0.41-0.87; P = 0.008) compared to the low/normal TSH group (n = 95). Although ORR was numerically higher in the high TSH group (27.6 vs 17.9%), the difference was not statistically significant (P = 0.23). Subgroup analyses indicated consistent benefits across most clinical strata. Thyroid immune-related adverse events occurred in 32/153 (20.9%), similarly between groups (20.7 vs 21.1%, P = 0.957), and were not significantly associated with either OS (HR 0.65, 95% CI: 0.38-1.11, P = 0.117) or PFS (HR 0.88, 95% CI: 0.54-1.44, P = 0.613) by time-varying Cox regression.

Conclusion: Elevated basal TSH levels are independently associated with improved survival in R/M NPC patients receiving KL-A167. Baseline TSH may serve as a simple, noninvasive biomarker for risk stratification and personalizing immunotherapy in this population.