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临床证据表明,在接受免疫检查点抑制剂治疗的癌症患者中,二甲双胍具有预后影响。

Clinical evidence for the prognostic impact of metformin in cancer patients treated with immune checkpoint inhibitors.

机构信息

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 211198, PR China.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 211198, PR China.

出版信息

Int Immunopharmacol. 2024 Jun 15;134:112243. doi: 10.1016/j.intimp.2024.112243. Epub 2024 May 11.

Abstract

BACKGROUND

Preclinical studies suggest that metformin might enhance the efficacy of immune checkpoint inhibitors (ICIs) and potentially influence the prognoses of cancer patients undergoing ICIs treatment. This study endeavors to assess the prognostic significance of metformin in cancer patients undergoing ICIs therapy, aiming to furnish evidence-based insights for clinical practice.

METHODS

A thorough literature search was conducted across electronic databases to encompass all potential records published before November 20th, 2023. A meta-analysis was executed utilizing Stata 17.0 to derive pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for both overall survival (OS) and progression-free survival (PFS).

RESULTS

A total of 22 studies encompassing 9,011 patients met the inclusion criteria. Meta-analyses revealed a significant correlation between metformin use and poorer OS (HR, 1.13; 95 %CI, 1.04-1.23; P = 0.004) rather than PFS (HR, 1.04; 95 %CI, 0.96-1.14; P = 0.345) among cancer patients undergoing ICIs treatment. Subgroup analysis delineated that the concurrent administration of metformin and ICIs significantly associated with adverse prognoses in the European population (OS: HR, 1.23; 95 %CI, 1.10-1.39; P = 0.001; PFS: HR, 1.14; 95 %CI, 1.02-1.28; P = 0.024).

CONCLUSION

Based on current clinical evidence, concomitant metformin use does not appear to improve the prognostic outcomes for cancer patients undergoing ICIs therapy and may potentially correlate with inferior prognoses. Further studies are imperative to comprehensively elucidate the impact of metformin within the realm of ICIs therapy.

摘要

背景

临床前研究表明,二甲双胍可能增强免疫检查点抑制剂(ICI)的疗效,并可能影响接受 ICI 治疗的癌症患者的预后。本研究旨在评估接受 ICI 治疗的癌症患者中二甲双胍的预后意义,为临床实践提供循证见解。

方法

通过电子数据库全面检索文献,囊括截至 2023 年 11 月 20 日之前发表的所有潜在记录。使用 Stata 17.0 进行荟萃分析,得出总体生存率(OS)和无进展生存率(PFS)的合并风险比(HR)及其 95%置信区间(CI)。

结果

共有 22 项研究纳入 9011 例患者符合纳入标准。荟萃分析显示,接受 ICI 治疗的癌症患者中,二甲双胍的使用与较差的 OS(HR,1.13;95%CI,1.04-1.23;P=0.004)而非 PFS(HR,1.04;95%CI,0.96-1.14;P=0.345)显著相关。亚组分析表明,二甲双胍与 ICI 的同时使用与欧洲人群中不良预后显著相关(OS:HR,1.23;95%CI,1.10-1.39;P=0.001;PFS:HR,1.14;95%CI,1.02-1.28;P=0.024)。

结论

基于现有临床证据,同时使用二甲双胍似乎并不能改善接受 ICI 治疗的癌症患者的预后结局,并且可能与预后不良相关。需要进一步研究来全面阐明二甲双胍在 ICI 治疗中的作用。

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