Immunotherapy-based combinations versus standard first-line and hypothyroidism risk

This is a comment on a beautiful meta-analysis by Buti and al on all available clinical data from randomized clinical trials evaluating the impact of immune checkpoint inhibitors (CKI) on the outcomes of patients with metastatic renal cell carcinoma (mRCC) in first-line setting. In their work, the authors showed that immunotherapy-based combinations were able to decrease the risk of death over the standard of care by 26% (HR 0.74; 95% confidence interval (CI) 0.60–0.92; p = 0.006), to decrease the risk of progression by 21% (HR 0.79; 95% CI 0.72–0.86; p < 0.00001), and to increase the relative risk of response by 40% (HR 1.40; 95% CI 1.11–1.77; p = 0.006). The authors did not report data on adverse events that are a relevant topic when a new treatment option arises. In particular, several studies showed that sunitinib is associated with a significant risk of developing all- and high-grade hypothyroidism [2], while endocrine dysfunctions among patients receiving CKI regimens were well described [3]. On the basis of these findings, which show a possible risk of hypothyroidism for both sunitinib and CKI, it could seem reasonable to extend the analyses performed by Buti et al. for the evaluation of the risk of hypothyroidism in patients who received immunotherapy‑based combinations versus sunitinib.