β受体阻滞剂在接受免疫检查点抑制剂治疗的晚期肝细胞癌中的应用结果。
Outcomes of beta blocker use in advanced hepatocellular carcinoma treated with immune checkpoint inhibitors.
作者信息
Wu Y Linda, van Hyfte Grace, Özbek Umut, Reincke Marlene, Gampa Anuhya, Mohamed Yehia I, Nishida Naoshi, Wietharn Brooke, Amara Suneetha, Lee Pei-Chang, Scheiner Bernhard, Balcar Lorenz, Pinter Matthias, Vogel Arndt, Weinmann Arndt, Saeed Anwaar, Pillai Anjana, Rimassa Lorenza, Naqash Abdul Rafeh, Muzaffar Mahvish, Huang Yi-Hsiang, Kaseb Ahmed O, Kudo Masatoshi, Pinato David J, Ang Celina
机构信息
Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
出版信息
Front Oncol. 2023 Feb 14;13:1128569. doi: 10.3389/fonc.2023.1128569. eCollection 2023.
BACKGROUND
In patients with cirrhosis, portal hypertension increases intestinal permeability, dysbiosis, and bacterial translocation, promoting an inflammatory state that can lead to the progression of liver disease and development of hepatocellular carcinoma (HCC). We aimed to investigate whether beta blockers (BBs), which can mediate portal hypertension, conferred survival benefits in patients treated with immune checkpoint inhibitors (ICIs).
METHODS
We conducted a retrospective, observational study of 578 patients with unresectable HCC treated with ICI from 2017 to 2019 at 13 institutions across three continents. BB use was defined as exposure to BBs at any time during ICI therapy. The primary objective was to assess the association of BB exposure with overall survival (OS). Secondary objectives were to evaluate the association of BB use with progression-free survival (PFS) and objective response rate (ORR) according to RECIST 1.1 criteria.
RESULTS
In our study cohort, 203 (35%) patients used BBs at any point during ICI therapy. Of these, 51% were taking a nonselective BB. BB use was not significantly correlated with OS (hazard ratio [HR] 1.12, 95% CI 0.9-1.39, = 0.298), PFS (HR 1.02, 95% CI 0.83-1.26, = 0.844) or ORR (odds ratio [OR] 0.84, 95% CI 0.54-1.31, = 0.451) in univariate or multivariate analyses. BB use was also not associated with incidence of adverse events (OR 1.38, 95% CI 0.96-1.97, = 0.079). Specifically, nonselective BB use was not correlated with OS (HR 0.94, 95% CI 0.66-1.33, = 0.721), PFS (HR 0.92, 0.66-1.29, = 0.629), ORR (OR 1.20, 95% CI 0.58-2.49, = 0.623), or rate of adverse events (OR 0.82, 95% CI 0.46-1.47, = 0.510).
CONCLUSION
In this real-world population of patients with unresectable HCC treated with immunotherapy, BB use was not associated with OS, PFS or ORR.
背景
在肝硬化患者中，门静脉高压会增加肠道通透性、微生物群失调和细菌易位，从而引发炎症状态，进而导致肝病进展和肝细胞癌（HCC）的发生。我们旨在研究可介导门静脉高压的β受体阻滞剂（BBs）是否能使接受免疫检查点抑制剂（ICIs）治疗的患者获得生存益处。
方法
我们对2017年至2019年期间在三大洲13家机构接受ICI治疗的578例不可切除HCC患者进行了一项回顾性观察研究。BB的使用定义为在ICI治疗期间的任何时间接触过BBs。主要目标是评估BB暴露与总生存期（OS）之间的关联。次要目标是根据RECIST 1.1标准评估BB使用与无进展生存期（PFS）和客观缓解率（ORR）之间的关联。
结果
在我们的研究队列中，203例（35%）患者在ICI治疗期间的任何时间使用过BBs。其中，51%服用的是非选择性BB。在单变量或多变量分析中，BB使用与OS（风险比[HR] 1.12，95%可信区间0.9 - 1.39，P = 0.298）、PFS（HR 1.02，95%可信区间0.83 - 1.26，P = 0.844）或ORR（优势比[OR] 0.84，95%可信区间0.54 - 1.31，P = 0.451）均无显著相关性。BB使用也与不良事件发生率无关（OR 1.38，95%可信区间0.96 - 1.97，P = 0.079）。具体而言，非选择性BB使用与OS（HR 0.94，95%可信区间0.66 - 1.33，P = 0.721）、PFS（HR 0.92，0.66 - 1.29，P = 0.629）、ORR（OR 1.20，95%可信区间0.58 - 2.49，P = 0.623）或不良事件发生率（OR 0.82，95%可信区间0.46 - 1.47，P = 0.510）均无相关性。
结论
在这一接受免疫治疗的不可切除HCC患者的真实世界人群中，BB使用与OS、PFS或ORR均无关联。
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