Background and Rationale: Immune checkpoint inhibitor (ICI) therapy is an expanding therapeutic option for hepatocellular carcinoma (HCC). Antibiotics (ATB) taken prior to or early during ICI therapy can impact immunotherapy efficacy across indications; however, the effect of ATB is undefined in HCC. Methods: In a large international cohort of 450 ICI recipients from Europe, North America, and Asia, we categorized patients according to timing of ATB focusing on exposure within −30 to +30 days from ICI (early immunotherapy period [EIOP]). EIOP was evaluated in association with overall survival (OS), progression-free survival (PFS), and best radiologic response using RECIST 1.1 criteria. Results: Our study comprised mostly cirrhotic (329, 73.3%) males (355, 79.1%) with a Child-Turcotte Pugh class of A (332, 73.9%), receiving ICI after 1 therapy line (251, 55.9%) for HCC of Barcelona clinic liver cancer stage C (325, 72.4%). EIOP (n = 170, 37.9%) was independent of baseline clinicopathologic features of HCC and correlated with longer PFS (6.1 vs. 3.7 months, log-rank p = 0.0135). EIOP+ patients had similar OS, overall response, and disease control rates (DCRs) compared to EIOP. The effect of EIOP persisted in landmark time analyses and in multivariable models, confirming the independent predictive role of EIOP in influencing PFS following adjustment for covariates reflective of tumor burden, liver function, and ICI regimen administered. In patients receiving programmed cell death-1 receptor/ligand inhibitors monotherapy, EIOP was also associated with higher DCRs (61.4% vs. 50.9%, p = 0.0494). Conclusions: Unlike other oncological indications, ATB in the 30 days before or after ICI initiation is associated with improved benefit from immunotherapy, independent of disease and treatment-related features. Evaluation of the immune microbiologic determinants of response to ICI in HCC warrants further investigation.
Liver Cancer

中文翻译：

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早期抗生素暴露不会损害肝细胞癌免疫治疗的治疗效果

背景和基本原理：免疫检查点抑制剂 (ICI) 疗法是肝细胞癌 (HCC) 的一种不断扩大的治疗选择。在 ICI 治疗之前或早期服用的抗生素 (ATB) 会影响各种适应症的免疫治疗效果；然而，ATB 对 HCC 的影响尚未明确。方法：在一个由来自欧洲、北美和亚洲的 450 名 ICI 接受者组成的大型国际队列中，我们根据 ATB 的时间对患者进行分类，重点是 ICI 后 -30 至 +30 天内的暴露（早期免疫治疗期 [EIOP]）。使用 RECIST 1.1 标准评估 EIOP 与总生存期 (OS)、无进展生存期 (PFS) 和最佳放射学反应的相关性。结果：我们的研究主要包括患有 Child-Turcotte Pugh A 级 (332, 73.9%) 的肝硬化 (329, 73.3%) 男性 (355, 79.1%)，在巴塞罗那 HCC 的 1 条治疗线 (251, 55.9%) 后接受 ICI临床肝癌 C 期 (325, 72.4%)。EIOP ( n = 170, 37.9%) 独立于 HCC 的基线临床病理学特征，并与更长的 PFS 相关（6.1 个月 vs. 3.7 个月，对数秩p= 0.0135)。与 EIOP 相比，EIOP+ 患者的 OS、总体反应和疾病控制率 (DCR) 相似。EIOP 的影响在里程碑时间分析和多变量模型中持续存在，证实了 EIOP 在调整反映肿瘤负荷、肝功能和 ICI 治疗方案的协变量后影响 PFS 的独立预测作用。在接受程序性细胞死亡 1 受体/配体抑制剂单药治疗的患者中，EIOP 还与更高的 DCR 相关（61.4% 对 50.9%，p = 0.0494）。结论：与其他肿瘤适应症不同，ICI 开始前或后 30 天内的 ATB 与免疫治疗获益的改善有关，与疾病和治疗相关特征无关。评估 HCC 对 ICI 反应的免疫微生物学决定因素值得进一步研究。
肝癌