Development of thyroid dysfunction is associated with clinical response to PD-1 blockade treatment in patients with advanced non-small cell lung cancer

• Main Authors: Hye In Kim, Mijin Kim, Se-Hoon Lee, So Young Park, Young Nam Kim, Hosu Kim, Min Ji Jeon, Tae Yong Kim, Sun Wook Kim, Won Bae Kim, Sang-We Kim, Dae Ho Lee, Keunchil Park, Myung-Ju Ahn, Jae Hoon Chung, Young Kee Shong, Won Gu Kim, Tae Hyuk Kim
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2018-01-01
• Series: OncoImmunology
• Subjects: biomarkers; immunotherapy; non-small cell lung cancer; programmed cell death 1; thyroid
• Online Access: http://dx.doi.org/10.1080/2162402X.2017.1375642

Purpose: Drugs that blockade interaction between programmed cell-death protein 1 (PD-1) and its ligand (PD-L1) are promising. Immune-related adverse events (irAEs) might be associated with favorable clinical outcomes, and thyroid dysfunction is one of the most common irAE. We evaluated the association of thyroid dysfunction during PD-1 blockade with the treatment efficacy in patients with non-small cell lung cancer (NSCLC). Experimental Design: A total 58 patients with stage IV NSCLC treated with PD-1 blockade were enrolled. Patients were categorized into thyroid dysfunction and euthyroid groups. Overall survival (OS) and progression-free survival (PFS) of the two groups were compared. Patients, tumor, and medication factors were adjusted using Cox proportional hazard modeling. Objective response rate (RR) and durable control rate were assessed according to the severity of thyroid dysfunction. Results: OS [median 118.0 (73.0-267.0) vs. 71.0 (28.0-160.0) days, log-rank P = 0.025] and PFS [118.0 (73.0-267.0) vs. 61.0 (28.0-130.0), log-rank P = 0.014] were longer in the thyroid dysfunction group. After adjustment, thyroid dysfunction was an independent predictive factor for favorable outcome [adjusted HR = 0.11 (95% CI) 0.01-0.92 for overall death; 0.38 (0.17-0.85) for disease progression]. The severity of thyroid dysfunction was associated with durable control rate (P for trend = 0.008). Conclusions: Thyroid dysfunction during PD-1 blockade is associated with treatment response and could provide supplementary information for immune monitoring in patients with advanced NSCLC.