Dysthyroidism during immune checkpoint inhibitors is associated with improved overall survival in solid tumors: Data-mining of 1,382 electronic patient records.

Abstract

2659 Background: Medical treatment of solid tumors cancer has irreversibly changed since the development of immune checkpoint inhibitors (ICI). However, immune-related adverse events (irAE) are challenging in routine practice. Dysthyroidism is the most common endocrine irAE and small series suggest that dysthyroidism might be associated with ICI efficacy. This led us to explore the association between ICI-induced dysthyroidism and overall survival (OS) in a large cohort of solid tumor patients (pts) using data mining of electronic patient records (EPR). Methods: ConSoRe is a new generation data analytics solution using natural language processing to search aggregated data and perform advanced data mining. It was used for data extraction from EPR of pts treated with ICI for solid tumors in Institut Paoli-Calmettes (Marseille Cancer Center, France), with validation using manual screening of 28.8% EPR. All dysthyroidism were verified and only dysthyroidism ICI-induced were retained. Survival analyses were performed by Kaplan-Meier method and compared using the log-rank test (survminer R package). In the uni/multivariate analysis, the Cox proportional-hazards model was used to estimate the variables associated with OS, using hazard ratio (HR) and its associated 95% confidence interval. Results: Data extraction identified 1,385 pts treated with ICI in 2011-2021. Dysthyroidism was observed in 90 pts (6.5%), including 22 hyperthyroidism (24%), 36 hypothyroidism (40%) and 32 hyperthyroidism and hypothyroidism (36%). In this cohort, 81 % of the dysthyroidism were related to PD(L)-1 inhibitors and 19 % to CTLA-4/PD(L)-1 inhibitors combination. No statistical difference was observed in term of tumor location between patients with or without dysthyroidism. Dysthyroidism was associated with improved OS (HR=0.46, 95%CI 0.29-0.70, p=0.0005) with a median OS of 65 months (mo) vs. 30 mo in patients without dysthyroidism. Survival impact of dysthyroidism was consistent using a 2-mo landmark analysis, fixed on median time to dysthyroidism. In multivariate analysis including sex, age, tumor localization, line numbers and type of ICI, dysthyroidism was independently associated with an improved OS (HR=0.49, 95%CI 0.32-0.75, p=0.001), as presented in the Table. Conclusions: Data mining identified a large number ICI-induced dysthyroidism, associated with an improved OS. The onset of dysthyroidism might help oncologist detecting patients more likely to benefit from ICI. [Table: see text]