Hypothyroidism induced by immune checkpoint inhibitors combined with antiangiogenic agents is associated with higher body mass index

Background: Recent studies have reported that the combination of immune checkpoint inhibitors (ICIs) and antiangiogenic agents could be a promising therapeutic strategy for advanced non-small cell lung cancer (NSCLC). However, both ICIs and antiangiogenic agents are associated with endocrine dysfunctions, mainly hypothyroidism. The risk of hypothyroidism is potentially increased with the combination of ICIs and antiangiogenic agents. This study aimed to investigate the incidence and risk factors of hypothyroidism in patients receiving combination therapy. Methods: We performed a retrospective cohort study of advanced NSCLC patients treated with ICIs and antiangiogenic agents at Tianjin Medical University Cancer Institute & Hospital from July 1, 2019, to December 31, 2021. Patients with normal thyroid function at baseline were enrolled, and information on the patients' characteristics before receiving combination therapy, including body mass index (BMI) and laboratory data, was obtained. Results: Among the 137 enrolled patients, 39 (28.5%) developed new-onset hypothyroidism, and 20 (14.6%) developed overt hypothyroidism. The incidence of hypothyroidism was significantly higher in obese patients than in patients with a low to normal BMI (P<0.001). Obese patients also had a higher incidence of overt hypothyroidism (P=0.016). Univariate logistic regression showed that BMI as a continuous variable was a significant risk factor for hypothyroidism [odds ratio (OR) 1.24, 95% confidence interval (CI): 1.10-1.42, P<0.001] and overt hypothyroidism (OR 1.17, 95% CI: 1.01-1.38, P=0.039). Multivariate logistic regression revealed that only BMI (OR 1.36, 95% CI: 1.16-1.61, P<0.001) and age (OR 1.08, 95% CI: 1.02-1.14, P=0.006) were significant risk factors for treatment-related hypothyroidism. Conclusions: The risk of hypothyroidism in patients receiving a combination of ICIs and antiangiogenic therapy is manageable, and a higher BMI is associated with a significantly increased risk of hypothyroidism. Therefore, clinicians should be aware of the development of hypothyroidism in obese advanced NSCLC patients during the administration of ICIs combined with antiangiogenic agents.