Introduction: Immune-Checkpoint Inhibitors (ICI) are frequently associated with thyroid-related adverse events (AE). Several studies analyzed thyroid disfunctions during ICI therapy, but many aspects remain to be characterized, especially for the most recent anti-PD-1 drugs. The aim of this study is to determine incidence and characteristics of PD-1 inhibitors associated thyroid dysfunction.
Methods: We retrospectively analyzed data of patients with advanced solid tumor treated with Programmed Death 1 (PD-1) inhibitors (Nivolumab, Pembrolizumab) in the Oncologic Unit B of Policlinico Umberto I of Rome, from January 2016 to December 2018. All patients performed baseline laboratory evaluations (TSH, FT3, FT4) that were repeated monthly over the duration of therapy.
Results: The cohort consisted of 126 patient, 66.7% males and 33.3% females with a mean age of 66.4±9.7 years, treated for Non Small Cell Lung Carcinoma (73%), Renal Cell Carcinoma (16.7%), Metastatic Melanoma (7.9%) or other tumors (2.4%). 107 received Nivolumab, 19 Pembrolizumab. Thyroid AE occurred in 31.7% of patients and were asymptomatic in the majority (CTCAE grade 1). None of the patients developed grade 34 thyroid AE requiring therapy discontinuation. Hypothyroidism occurred in 17.5% of patients: in 15% it was subclinical (high TSH with normal free circulating hormones) and in 2.5% overt hypothyroidism. Mean TSH concentration at the time hypothyroidism was diagnosed was 10.7±7.26 mUI/ml. Hyperthyroidism was observed in 14.3% of patients: in 9.5% subclinical and in 4.8% overt. The rate of thyroid AE was similar in Nivolumab (31.8%) compared to Pembrolizumab (31.6%). The median time of onset of thyroid AE was 6.5±8.1 weeks (range 338): 6±9.6 (438) for hypothyroidism, and 7±5.7 (range 326) for hyperthyroidism. The majority of AE appeared within the first 3 month (72.5%), none developed after 10 months. Of the 22 patients with hypothyroidism, 63.6% had received a previous treatment with tyrosine-kinase inhibitors (TKI). Logistic regression analysis showed that pre-treatment with TKI was the most potent predisposing factor (OR 8.19, 95%CI: 2.45 to 27.37, P=0.001) followed by female gender (OR 3.29, 95%CI: 1.26 to 8.57, P=0.015).
Conclusion: Thyroid AE are common during PD-1 inhibitors therapy and usually occur within the first 3 months of treatment, especially in subjects pretreated with TKI. Serial measurement of thyroid function is strictly recommended, especially in these patients, as thyroid disorders can be asymptomatic. No differences were found in thyroid effects between Nivolumab and Pembrolizumab.
18 - 21 May 2019
European Society of Endocrinology