Thyroid dysfunction caused by immune-checkpoint-inhibitors improves cancer outcomes

A common immune-related adverse event (irAE) with immune checkpoint inhibitors (ICIs) is thyroid dysfunction (TD-irAEs). The clinical presentation can be varied and its association with prognosis remains unclear. We investigated the characteristics of TD-irAEs and their association with clinical outcomes among cancer patients treated with ICIs in a real-life setting. Response to treatment was assessed using RECIST v1.1. We calculated the probability of recurrence and survival associated with TD-irAEs using multivariable-adjusted regression and Cox proportional hazards models. In this single-centre retrospective analysis, we included 238 patients (72% male) with median age of 69.5 years. Primary tumours were melanoma (23.1%), lung (60.5%), or urothelial cancer (16.4%), treated with atezolizumab (23.1%), pembrolizumab (44.5%), ipilimumab (0.4%) and/or nivolumab (25.6%). Seventy (29%) patients developed TD-irAEs in a median time of 69 days (41-181). The incidence of TD-irAEs with combination therapy was higher than with monotherapy (67% vs. 6.3%, p=0.011). TD-irAE patients showed a higher objective response rate (ORR) than those without TD-irAEs (60% vs. 42.3%, p=0.013) and longer overall survival (OS) 45 vs. 16 months, p<0.006. Patients who developed TD-irAEs 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 tumour, or ICI regimen. TD-irAEs occur in nearly 30% of our patients receiving ICIs. In our analysis, TD-irAEs appeared to be associated with higher ORR and longer OS and showed a reduction in the risk of progression and mortality.