Endocrine Abstracts

Introduction: Immune checkpoint inhibitors (ICIs) are an effective treatment for advanced cancer, but they are not free from immune-related adverse events (irAEs). A common irAES is thyroid dysfunction (TD-irAEs) and, as such, may influence patient survival and response to ICIs.

Objetives: The aim was to determine the incidence and characteristics of TD-irAEs among patients with advanced cancer treated with ICIs in a real-life setting and to investigate the association between TD-irAEs and response to treatment.

Methods: A single-center retrospective analysis of TD-irAEs in patients with advanced cancer treated with ICIs. We analyzed the development of TD and its association with the response to treatment assessed using RECIST v1.1 criteria. We calculated the odds of recurrence associated with TD-irAEs using multivariable adjusted regression and overall survival associated with TD-irAEs using multivariable adjusted Cox proportional hazards models.

Results: We included 238 patients (72% male; median age 69.5 years, range 63-76) with melanoma, lung or urothelial cancer, treated with Atezolizumab, Pembrolizumab, Ipilimumab and/or Nivolumab. Of them, 70 (29%) patients developed TD-irAEs in a median time of 69 days (range 41-181). The most frequent TD-irAEs was subclinical hypothyroidism (41%), followed by subclinical thyrotoxicosis (24%), overt hypothyroidism (17%) and hyperthyroidism (17%). Patients who developed TD-irAEs were younger (P = 0.030) than those who did not. No significant differences between groups were found for sex (P = 0.145) or type of primary tumor (P = 0.051). The incidence of TD-irAEs in patients treated with combination therapy (Nivolumab + Ipilimumab, 67%) was significantly higher than that in patients treated with any ICI in monotherapy. Compared with patients who did not develop TD-irAEs, those in the TD-irAEs group had a relative reduction of 77% (OR 0.23, 95% CI 0.11-0.47) in the risk of progression and of 47% in the risk of mortality (HR 0.53, 95% CI 0.36-0.80), independent of age, sex, primary tumor, or type of ICI treatment.

Conclusions: TDirAEs occur in nearly 30% of patients receiving ICI treatment. Most TD-irAEs were mild and easily controlled. The occurrence of TD-irAEs appeared to be associated with improved response to ICIs as well as improved survival. These findings may reinforce the clinical relevance of monitoring thyroid function, as such monitoring could be an independent prognostic indicator of antitumor response and survival among oncologic patients on ICI treatment.