| Literature DB >> 31423288 |
Tomoki Sakakida1, Takeshi Ishikawa1,2, Junji Uchino3, Yusuke Chihara2,3, Satoshi Komori4, Jun Asai4, Tsukasa Narukawa5, Akihito Arai6, Tsutomu Kobayashi7, Hiroaki Tsunezuka8, Toshiyuki Kosuga9, Hirotaka Konishi9, Fumiya Hongo5, Masayoshi Inoue8, Shigeru Hirano6, Osamu Ukimura5, Yoshito Itoh1, Tetsuya Taguchi2,10, Koichi Takayama3.
Abstract
Programmed cell death protein-1 (PD-1) blockade therapy has improved outcomes in the treatment of advanced cancers. The therapy is well-tolerated, although it occasionally causes immune-related adverse events (irAEs). Thyroid dysfunction is one of the most common irAEs seen. Our aim was to clarify the clinical characteristics of thyroid dysfunction induced by PD-1 blockade and its association with the therapeutic effect of the treatment in advanced cancers. A total of 174 patients who received nivolumab or pembrolizumab for metastatic or unresectable advanced cancers were included in this retrospective study. The patients were divided into two groups: The thyroid dysfunction group and the euthyroid group. In the present study, the clinical characteristics, the association with anti-thyroid antibodies, as well as the progression-free survival (PFS) and overall survival (OS) were estimated. An adjusted Cox proportional hazard regression model was used to evaluate prognostic factors for OS and PFS. This study showed that 25 out of 150 patients (16.7%) developed immune-related thyroid dysfunction. Hypothyroidism occurred in the early stage of the clinical course (median: 12 weeks); subsequently, 9 of the 25 patients underwent a transient period of hyperthyroidism, all with mild symptoms. The presence of positive anti-thyroid antibodies at baseline was significantly higher in the thyroid dysfunction group (13/22) than in the euthyroid group (18/100, P=0.0002). Moreover, PFS (median: 66 vs. 27 weeks, hazard ratio (HR): 0.50, 95% CI: 0.26-0.89, P=0.02) and OS (median 156 vs. 59 weeks, HR: 0.34, 95% CI: 0.13-0.75, P=0.01) were significantly longer in the thyroid dysfunction group than in the euthyroid group. Multivariable analysis also revealed that thyroid dysfunction was an independent prognostic factor for OS (HR: 0.42, 95% CI: 0.16-0.97, P=0.04). These findings may enable the early recognition and appropriate management of thyroid dysfunction, and help in maximizing the therapeutic effect of PD-1 blockade.Entities:
Keywords: PD-1; hyperthyroidism; hypothyroidism; irAEs; nivolumab; pembrolizumab; thyroid dysfunction
Year: 2019 PMID： 31423288 PMCID： PMC6607381 DOI： 10.3892/ol.2019.10466
Source DB: PubMed Journal: Oncol Lett ISSN： 1792-1074 Impact factor: 2.967