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皮质类固醇会影响恶性肿瘤的免疫治疗疗效吗?——一项系统评价。

Do corticosteroids affect immunotherapy efficacy in malignancy? - A systematic review.

机构信息

Alan Walker Cancer Centre, Royal Darwin Hospital, Darwin, 0810, Northern Territory, Australia.

School of Medicine, Griffith University, Gold Coast, Queensland, Australia.

出版信息

Cancer Med. 2024 Sep;13(18):e70254. doi: 10.1002/cam4.70254.

Abstract

BACKGROUND

Early studies indicated that corticosteroids may limit the survival benefit from immunotherapy. We conducted this systematic review to evaluate the effect corticosteroids have on immunotherapy in patients with malignancy, when adjusted for potentially confounding effects of corticosteroids given for palliative indications.

METHODS

Three electronic databases (PubMed, Embase and Medline) were searched on 1 February 2023. Studies that measured response or survival to immunotherapy in people receiving corticosteroids for non-cancer indications compared to either no corticosteroids or corticosteroids for cancer-related indications were included. Studies exclusively evaluating the effect of corticosteroids administered for immune-related adverse events (irAE) were excluded to avoid immortal time bias. Pooled odds and hazard ratios with 95% confidence intervals (CI) were calculated using a random effects model. Study heterogeneity was assessed using the I statistic, and publication bias was evaluated by funnel plot and Egger's regression model.

RESULTS

Eight thousand four hundred and twenty-six titles were identified on our search. Eight studies met our inclusion criteria for meta-analysis. Administration of corticosteroids does not have a statistically significant effect on survival and response to immunotherapy when administered for non-cancer-related indications, with a pooled odds ratio for overall response rate 1.01 (95% CI 0.64-1.60); pooled hazard ratio (HR) for progression free survival 0.87 (95% CI 0.68-1.12); and pooled HR for overall survival 0.79 (95% CI 0.59-1.05).

CONCLUSION

This systematic review indicates that administration of corticosteroids does not affect response to immunotherapy nor survival outcomes, when removing confounding palliative corticosteroid indications. These results are limited by the retrospective nature of the studies included, small sample sizes, lack of information about corticosteroid dosing and the inclusion of irAE in two of the studies which could bias the results.

摘要

背景

早期研究表明,皮质类固醇可能会限制免疫疗法的生存获益。我们进行了这项系统评价,以评估在调整了皮质类固醇用于姑息治疗指征的潜在混杂影响后,皮质类固醇对恶性肿瘤患者免疫治疗的影响。

方法

我们于 2023 年 2 月 1 日在三个电子数据库(PubMed、Embase 和 Medline)中进行了检索。纳入了比较非癌症指征下接受皮质类固醇治疗的人群与未接受皮质类固醇治疗或癌症相关指征下接受皮质类固醇治疗的人群对免疫治疗的反应或生存的研究。为避免 Immortal Time Bias( Immortal Time Bias:在评估药物或治疗对某一结果的影响时,因为患者在开始接受治疗之前的一段时间内处于某种状态,而这段时间内的结果不会受到治疗的影响,从而导致对治疗效果的估计出现偏差。),我们排除了专门评估因免疫相关不良反应(irAE)而给予皮质类固醇的影响的研究。使用随机效应模型计算了合并的优势比和 95%置信区间(CI)。使用 I 统计量评估研究异质性,并通过漏斗图和 Egger 回归模型评估发表偏倚。

结果

我们的检索共确定了 8426 个标题。有 8 项研究符合我们的荟萃分析纳入标准。当用于非癌症相关指征时,皮质类固醇的使用并不会对生存和免疫治疗的反应产生统计学上的显著影响,总反应率的合并优势比为 1.01(95%CI 0.64-1.60);无进展生存期的合并危险比(HR)为 0.87(95%CI 0.68-1.12);总生存期的合并 HR 为 0.79(95%CI 0.59-1.05)。

结论

这项系统评价表明,在消除混杂的姑息性皮质类固醇指征后,皮质类固醇的使用不会影响免疫治疗的反应或生存结果。这些结果受到纳入研究的回顾性性质、样本量小、皮质类固醇剂量信息缺乏以及两项研究中包含 irAE 的限制,这些可能会影响结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09cd/11420628/35cb92f18905/CAM4-13-e70254-g002.jpg

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