Background: Thyroid dysfunction is a common adverse effect of VEGF TKIs. There are conflicting reports on survival benefit in association with hypothyroidism. Moreover, severity of hypothyroidism has not been correlated with survival outcomes in mRCC. Methods: From a single institutional database (2004-2013), we identified pts with mRCC receiving VEGF TKIs. Serial serum thyroid-stimulating hormone (TSH) values were collected, and at least two consecutive TSH values were required for inclusion. Progression free survival (PFS) and overall survival (OS) were assessed. Univariate and multivariate analyses were performed using the Kaplan-Meier method and COX Proportional Hazard models. Results: Of 125 pts treated with a VEGF TKI, 70 pts were eligible (median age 59 yrs, males 70%). The majority of pts had clear cell histology (74.3%) and were in the MSKCC (71.4%)and Heng (52.9%) intermediate-risk groups. Pts received the following TKIs: sunitinib (77.1%), sorafenib (12.9%), pazopanib (8.6%), and axitinib (1.4%). Thyroid dysfunction occurred in 45.7% of pts, of which 21.4% of pts had a TSH > 10 mIU/L during treatment. The median PFS and OS were significantly longer in pts with a TSH > 10 mIU/L compared with those with lower TSH values (Table). In the multivariate analysis, including age, sex, hand-foot syndrome (HFS), and risk criteria, a TSH > 10 mIU/L during TKI treatment remained significant for improvements in PFS and OS (PFS: HR 0.31, CI 0.11-0.73, p=0.0063; OS: HR 0.19, CI 0.04-0.58, p=0.0021). Conclusions: The severity of hypothyroidism (TSH > 10 mIU/L) directly correlates with improved survival outcomes in pts with mRCC treated with VEGF TKIs.

Appreviations: ULN, upper limit of normal; n/a, not achieved.