[Clinical Features of PD-1/PD-L1 Inhibitors-Related Thyroid Dysfunction in Lung Cancer Patients and Their Predictive Value for Therapeutic Efficacy]

【肺癌患者PD-1/PD-L1抑制剂相关甲状腺功能障碍的临床特征及其对治疗效果的预测价值】

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Abstract

OBJECTIVE: To investigate the clinical features of thyroid dysfunction in lung cancer patients treated with programmed cell death receptor-1 (PD-1) or programmed cell death receptor-ligand 1 (PD-L1) and their value for predicting therapeutic efficacy. METHODS: Lung cancer patients treated with PD-1/PD-L1 inhibitors at West China Hospital, Sichuan University between March 2018 and September 2022 were retrospectively enrolled. Data concerning the medical records, therapeutic efficacy, and thyroid function indicators of the patients were retrieved from the hospital electronic medical record information system. The data were then analyzed to identify risk factors and predictive factors for immune-related adverse events (irAEs) of the thyroid. The predictive value of thyroid irAEs for treatment efficacy and prognosis was assessed. Objective response rate (ORR) was defined as the indicator for therapeutic efficacy and progression-free survival (PFS) was defined as the prognostic indicator. RESULTS: A total of 368 lung cancer patients were enrolled. Among them, 31.5% (116/368) developed thyroid irAEs. According to the results of logistic regression analysis, baseline thyroid stimulating hormone (TSH) concentration and baseline positive results for thyroglobulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb) were risk factors for thyroid dysfunction caused by PD-1/PD-L1 inhibitors. Among the three measures, baseline TPOAb concentration demonstrated good predictive value for thyroid irAEs, with an area under the receiver-operating characteristic (ROC) curve (AUC) of 0.745. Patients with thyroid irAEs had a longer median PFS (16.0 months vs. 9.7 months, P < 0.001) and a higher ORR (55.2% vs. 34.9%, P < 0.001) compared to those without thyroid irAEs. Patients with thyroid irAEs had a better ORR than those without thyroid irAEs did. It was more likely for patients with thyroid irAEs to achieve an objective response compared to those without thyroid irAEs (odds ratio [OR] = 2.29; 95% CI, 1.46-3.60). CONCLUSION: In lung cancer patients treated with the PD-1/PD-L1 inhibitors, the TPOAb antibody demonstrates good predictive value for thyroid irAEs. Patients who develop thyroid irAEs have better treatment outcomes and prognosis.

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