Immune-Related Thyroid Dysfunction in PD-L1 High Non-Oncogene-Addicted NSCLC Treated with First-Line Pembrolizumab:...

Area of Science:

• Oncology
• Immunotherapy
• Endocrinology

Background:

• Pembrolizumab monotherapy benefits a subset of patients with metastatic non-small cell lung cancer (NSCLC) and high PD-L1 expression (TPS ≥ 50%).
• Immune-related thyroid dysfunction (irTD) is a known side effect of PD-1/PD-L1 blockade, but its predictive significance for treatment outcomes is unclear.

Purpose of the Study:

• To investigate the incidence and predictive value of immune-related thyroid dysfunction (irTD) in patients with metastatic NSCLC treated with first-line pembrolizumab.
• To assess the association between irTD and progression-free survival (PFS) in this patient population.

Main Methods:

• Retrospective, single-center study of 363 patients with metastatic NSCLC (PD-L1 TPS ≥ 50%) treated with first-line pembrolizumab.
• Thyroid function tests were monitored regularly; irTD was defined by laboratory abnormalities and classified by onset timing (early ≤90 days, late >90 days).
• Progression-free survival (PFS) was analyzed using Kaplan-Meier and Cox proportional hazards models, including landmark analyses to mitigate immortal-time bias.

Main Results:

• Immune-related thyroid dysfunction (irTD) occurred in 30.3% of patients, with a median onset of 114 days.
• Patients who developed irTD had significantly longer PFS (26.33 months) compared to those without irTD (6.16 months; HR 0.378, p < 0.001).
• Landmark analyses at 3 and 6 months confirmed the PFS benefit associated with irTD; onset timing did not significantly impact PFS.

Conclusions:

• Immune-related thyroid dysfunction (irTD) is a frequent and manageable complication in PD-L1-high metastatic NSCLC treated with pembrolizumab.
• The occurrence of irTD is strongly associated with improved PFS, suggesting it may serve as a predictive biomarker for effective immune activation.
• Further prospective studies are warranted to validate irTD as a clinical biomarker in this setting.