Yan Xuebing, Liu Peipei, Li Donglin, Hu Ru, Tao Mingyang, Zhu Siyuan, Wu Wenjuan, Yang Mengxue, Qu Xiao
Department of Oncology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.
Department of Oncology, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou University, Yangzhou, China.
Int Immunopharmacol. 2022 Dec;113(Pt A):109383. doi: 10.1016/j.intimp.2022.109383. Epub 2022 Oct 28.
Cancer immunotherapy based on immune checkpoint inhibitors (ICIs) has made encouraging achievements in both clinical trials and real-world studies. The β-blockers, as common concomitant medications in clinical practice, have been suggested to exert anti-cancer effects in various human malignancies. This study aimed to clarify the prognostic impact of β-blockers in solid cancer patients receiving ICI therapy.
A systematic literature review and meta-analysis was firstly performed based on databases including PubMed, Cochrane Library, Web of Science, Embase, and Clinicaltrials.gov before August 1th 2022. The association of β-blocker use with overall survival (OS) or progression-free survival (PFS) was determined using the hazard ratios (HRs) coupled with 95% confidence intervals (CIs). Then, a retrospective study enrolling 194 patients was performed to validate the results of the meta-analysis.
A total of 11 studies enrolling 10,156 patients were included in the meta-analysis. The pooled analysis demonstrated β-blocker use was not significantly correlated with either OS (HR = 0.97(0.85-1.11)) or PFS (HR = 0.98(0.90-1.06)). Similar results were also observed in the subgroup analysis stratified by cancer type, age, sample size and ICI therapy, except for the OS (HR = 0.61(0.45-0.83)) and PFS (HR = 0.65(0.44-0.96)) in the studies with sample size less than 200. The retrospective study indicated no significant correlation between β-blocker use and the clinical outcome in the entire cohort and lung cancer subgroup. However, β-blocker use was found to be significantly associated with better objective response to ICI-based therapy in the entire cohort (odds ratio (OR) = 0.42(0.19-0.94), p = 0.036) and lung cancer subgroup (OR = 0.25(0.08-0.83), p = 0.024).
Although both our up-to-date meta-analysis and retrospective study suggested β-blocker use has no significant impact on the overall prognosis of solid cancer patients receiving ICIs, β-blocker use may be associated with improved anti-cancer efficacy of ICIs. Considering study limitations, more clinical validations and mechanism investigations are of great necessity for clarifying the role of β-blockers in ICI-based therapy.
基于免疫检查点抑制剂（ICI）的癌症免疫疗法在临床试验和真实世界研究中均取得了令人鼓舞的成果。β受体阻滞剂作为临床实践中常用的伴随用药，已被证明在多种人类恶性肿瘤中发挥抗癌作用。本研究旨在阐明β受体阻滞剂对接受ICI治疗的实体癌患者的预后影响。
首先基于包括PubMed、Cochrane图书馆、Web of Science、Embase和Clinicaltrials.gov在内的数据库，在2022年8月1日之前进行系统的文献综述和荟萃分析。使用风险比（HR）和95%置信区间（CI）确定β受体阻滞剂使用与总生存期（OS）或无进展生存期（PFS）之间的关联。然后，进行一项纳入194例患者的回顾性研究以验证荟萃分析的结果。
荟萃分析共纳入11项研究，涉及10156例患者。汇总分析表明，使用β受体阻滞剂与OS（HR = 0.97（0.85 - 1.11））或PFS（HR = 0.98（0.90 - 1.06））均无显著相关性。在按癌症类型、年龄、样本量和ICI治疗分层的亚组分析中也观察到类似结果，但样本量小于200的研究中的OS（HR = 0.61（0.45 - 0.83））和PFS（HR = 0.65（0.44 - 0.96））除外。回顾性研究表明，在整个队列和肺癌亚组中，β受体阻滞剂的使用与临床结局无显著相关性。然而，发现在整个队列（优势比（OR）= 0.42（0.19 - 0.94），p = 0.036）和肺癌亚组（OR = 0.25（0.08 - 0.83），p = 0.024）中，使用β受体阻滞剂与基于ICI的治疗的更好客观反应显著相关。
尽管我们最新的荟萃分析和回顾性研究均表明，使用β受体阻滞剂对接受ICI治疗的实体癌患者的总体预后无显著影响，但使用β受体阻滞剂可能与ICI的抗癌疗效改善有关。考虑到研究局限性，进行更多的临床验证和机制研究对于阐明β受体阻滞剂在基于ICI的治疗中的作用非常必要。
