The combination of atezolizumab and bevacizumab (Ate/Bev) has become the new standard of care as first-line systemic therapy for unresectable hepatocellular carcinoma (HCC). Although several studies have reported thyroid dysfunction after treatment with immune checkpoint inhibitors, the clinical and immunological significance of thyroid dysfunction in patients with Ate/Bev has not been comprehensively addressed. In this study, we aim to comprehensively evaluate the clinical and immunological implications of thyroid dysfunction in unresectable HCC patients treated with Ate/Bev.
This study enrolled 208 patients with unresectable HCC treated with Ate/Bev from three Korean cancer centers. Thyroid adverse events (AEs) were reviewed, and cytokines and T cells in the blood samples were analyzed at baseline. For external validation, we analyzed clinical outcomes according to thyroid AEs in patients treated with Ate/Bev in the IMbrave150 study.
Forty-one (19.7%) out of 208 patients experienced thyroid dysfunction (hypothyroidism [17.3%] and thyrotoxicosis [5.8%]) after Ate/Bev treatment. The median time to onset of hypothyroidism and thyrotoxicosis after Ate/Bev treatment were 3.5 months and 1.3 months, respectively. Patients with thyroid AEs demonstrated significantly better results in terms of progression-free survival, overall survival, and objective response rate than those without thyroid AEs. These findings were still consistent even after adjusting for confounding factors. Furthermore, favorable survival outcomes in patients with thyroid AE were also validated in a cohort of IMbrave150 patients. While patients with thyrotoxicosis showed significantly lower level of baseline IL-6, patients with hypothyroidism did not show significant differences in circulating cytokine levels and CD8+ T cell fractions.
A fraction of patients with HCC treated with Ate/Bev experienced thyroid dysfunction, and the development of thyroid AEs was associated with favorable clinical outcomes.
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This publication is based on research using data from data contributors Roche that has been made available through Vivli, Inc. Vivli has not contributed to or approved, and is not in any way responsible for, the contents of this publication.
This work was supported by the National Research Foundation of Korea [NRF] grants funded by the Korean government [MSIT] [NRF-2023R1A2C2004339 to HJC, NRF-2023R1A2C2006375 to CK].
All authors have declared no conflicts of interest.