Thyroid dysfunction during PD‑1 inhibitor treatment in patients with cancer: Incidence and association with progression‑free survival

Abstract

The use of programmed cell death-1 (PD-1) inhibitors has recently been approved in China. As a consequence, the identification of relevant prognostic markers that can assess the efficacy of these compounds is required. Therefore, the present study aimed to explore the incidence of thyroid dysfunction and its ability to predict progression-free survival (PFS) in Chinese patients with cancer who received PD-1 inhibitor treatment. Data from 72 patients with cancer who received treatment with PD-1 inhibitors alone or in combination with chemotherapy or targeted drugs were analyzed. Moreover, the expression levels of free triiodothyronine, thyroxine, and thyrotropin during treatment were assessed to evaluate thyroid dysfunction. A total of 26 (36.1%) patients who had received PD-1 inhibitors developed thyroid dysfunction. Specifically, the incidence of thyroid dysfunction was 35.6% in patients with lung cancer, 25.0% in patients with malignant melanoma, and 46.7% in patients with other types of cancer. In addition, the median PFS was 7.0 (95% confidence interval, 4.9-9.1) months, whereas the 1-and 2-year PFS rates were 35.1 and 26.2%, respectively. Generally, patients with thyroid dysfunction exhibited longer PFS compared with those without thyroid dysfunction (P=0.001). Subgroup analyses were subsequently performed, which demonstrated that thyroid dysfunction was associated with longer PFS in patients with malignant melanoma (P=0.039) and other types of cancer (P=0.002), but not in those with lung cancer (P=0.083). These findings were noted in patients who received PD-1 inhibitor monotherapy (P=0.003), but not PD-1 inhibitor plus chemotherapy (P=0.172) or PD-1 inhibitor plus targeted therapy (P=0.582). Finally, thyroid dysfunction [P=0.001; hazard ratio (HR)=0.260] and PD-1 inhibitor monotherapy (P=0.015; HR=2.231) were identified as independent factors that could predict PFS. In conclusion, the present study demonstrated that thyroid dysfunction during PD-1 inhibitor treatment could be used as a potential marker for the prognosis of favorable PFS in patients with cancer.

Immune-related thyroid dysfunction in patients with non-small cell lung cancer

“…Similarly, favorable OS and PFS have been reported in patients with irTDs and NSCLC ( 18 ). In contrast, irTDs were considered without better OS and (or) PFS in the patients with NSCLC in a few studies ( 21 , 22 ). No statistically significant difference was observed in the OS and PFS between patients with irTDs and euthyroid patients in our study, suggesting that irTDs had no obvious impact on the clinical outcomes of patients with NSCLC treated with ICIs.…”

“…However, the impact of irTDs on the clinical outcomes of patients with NSCLC remains unclear. Better overall survival (OS) and/or progression-free survival (PFS) in malignancies have been described in some research ( 16 - 20 ), while no influence has been reported ( 21 , 22 ).…”

Thyroid dysfunction (TD) induced by PD-1/PD-L1 inhibitors in advanced lung cancer

“…However, Percik et al [ 2 ] reported that there was a correlation between the occurrence of TD and good outcome and prognosis when PD-1/PD-L1 inhibitors were used to treat renal cancer (HR = 0.19, 95% CI [0.06–0.60], p = 0.005), whereas no correlation was observed in lung cancer. D'Aiello [ 4 ] and Wu et al [ 103 ] also found no significant differences in treatment response and prognostic Indicators of survival between TD and no-TD groups when ICIs were used to treat lung cancer.…”

Enhancing Effector Jurkat Cell Activity and Increasing Cytotoxicity against A549 Cells Using Nivolumab as an Anti-PD-1 Agent Loaded on Gelatin Nanoparticles

“…In contrast, the opposition or antagonism of PD-1 has demonstrated a significant boost in anti-tumor immunity, indicating that blocking PD-1 can potentially unleash an effective attack on cancer cells by enhancing the T cell response against them [ 11 , 12 ]. Such intricate molecular pathways offer promising insights into new therapeutic strategies for treating complex medical conditions through modulation of this key regulatory checkpoint molecule, PD-1 [ 13 ].…”