Introduction Atezolizumab and bevacizumab (Ate/Bev) combination has become the new first-line systemic therapy for unresectable hepatocellular carcinoma (HCC). Although several studies reported thyroid dysfunction after treatment with immune checkpoint inhibitors, the clinical and immunological significance of thyroid dysfunction in patients treated with Ate/Bev has not been comprehensively addressed. We aimed to comprehensively evaluate the clinical and immunological implications of thyroid dysfunction in unresectable HCC patients treated with Ate/Bev. Methods We 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. Results Forty-one (19.7%) out of 208 patients experienced thyroid dysfunction (hypothyroidism [17.3%] and thyrotoxicosis [5.8%]) after Ate/Bev treatment. Median time to onset of hypothyroidism and thyrotoxicosis after Ate/Bev treatment was 3.5 and 1.3 months, respectively. Patients with thyroid AEs demonstrated significantly better 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 AEs were also validated in a cohort of IMbrave150 patients. While patients with thyrotoxicosis showed a significantly lower level of baseline IL-6, those with hypothyroidism did not show significant differences in circulating cytokine levels and CD8+ T-cell fractions. Conclusions 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.

中文翻译：

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阿特朱单抗和贝伐单抗后的甲状腺功能障碍与肝细胞癌的良好结果相关。


简介 Atezolizumab 和贝伐单抗 (Ate/Bev) 组合已成为不可切除的肝细胞癌 (HCC) 的新一线全身疗法。尽管一些研究报告了免疫检查点抑制剂治疗后出现甲状腺功能障碍，但接受 Ate/Bev 治疗的患者甲状腺功能障碍的临床和免疫学意义尚未得到全面解决。我们的目的是全面评估接受 Ate/Bev 治疗的不可切除 HCC 患者甲状腺功能障碍的临床和免疫学影响。方法 我们招募了来自三个韩国癌症中心的 208 名接受 Ate/Bev 治疗的不可切除 HCC 患者。回顾了甲状腺不良事件 (AE)，并在基线时分析了血样中的细胞因子和 T 细胞。为了进行外部验证，我们根据 IMbrave150 研究中接受 Ate/Bev 治疗的患者的甲状腺 AE 分析了临床结果。结果 208 名患者中有 41 名（19.7%）在 Ate/Bev 治疗后出现甲状腺功能障碍（甲状腺功能减退症 [17.3%] 和甲状腺毒症 [5.8%]）。 Ate/Bev 治疗后出现甲状腺功能减退症和甲状腺毒症的中位时间分别为 3.5 个月和 1.3 个月。与没有甲状腺 AE 的患者相比，患有甲状腺 AE 的患者表现出明显更好的无进展生存期、总生存期和客观缓解率。即使在调整混杂因素后，这些发现仍然是一致的。此外，甲状腺 AE 患者良好的生存结果也在 IMbrave150 患者队列中得到了验证。虽然甲状腺毒症患者的基线 IL-6 水平显着降低，但甲状腺功能减退症患者的循环细胞因子水平和 CD8+ T 细胞分数没有显着差异。 结论 接受 Ate/Bev 治疗的部分 HCC 患者出现甲状腺功能障碍，甲状腺 AE 的发生与良好的临床结果相关。