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随机对照试验中免疫检查点抑制剂治疗癌症患者的健康相关生活质量:系统评价和荟萃分析。

Health-related quality of life in cancer patients treated with immune checkpoint inhibitors in randomised controlled trials: A systematic review and meta-analysis.

机构信息

Oncologia Medica 2, IRCCS Ospedale Policlinico San Martino, Genova, Italy; Department of Internal Medicine and Medical Specialties, School of Medicine, University of Genoa, Genoa, Italy.

Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy.

出版信息

Eur J Cancer. 2021 Dec;159:154-166. doi: 10.1016/j.ejca.2021.10.005. Epub 2021 Nov 6.

Abstract

BACKGROUND

Immune checkpoint inhibitors (ICIs) have revolutionised clinical practice in oncology in the last years, leading to a survival benefit in several tumour types. To investigate whether these benefits are associated with improved quality of life, we conducted a systematic review and meta-analysis comparing patient-reported outcomes (PROs) between ICIs and standard chemotherapy (CT) in patients with advanced solid tumours.

METHODS

Clinical trials comparing the efficacy of ICIs (either programmed death receptor-1 and programmed death-ligand 1 inhibitors or cytotoxic T-lymphocyte antigen 4 inhibitors, as single agent or in combination) versus CT were included. Trials evaluating treatment with ICIs plus CT versus CT alone were also included, whereas studies in which the control arm included other anticancer agents (such as targeted therapy and other ICIs) or placebo alone were excluded. The aim of our meta-analysis was to compare PROs in subjects treated with ICIs or ICIs plus CT (intervention) with those reported by patients receiving CT (control). The co-primary endpoints were time from baseline to first deterioration in PROs, defined as the time from baseline to the first clinically significant deterioration in PROs, and the changes in PROs from baseline to follow-up between ICI and CT treatment groups (PROSPERO registration number CRD42021247440).

RESULTS

A total of 8341 patients from 17 randomised trials of ICI versus CT were included in the analysis. Treatment with ICI delayed clinical deterioration over standard CT in Global Health Status/QoL EORTC QLQ-C30 (hazard ratio [HR] 0.81; 95% confidence interval [CI], 0.74-0.89), and in both EQ-5D utility index (HR 0.65; 95% CI, 0.52-0.82) and EQ-5D visual analogue scale (VAS; HR 0.70; 95% CI, 0.61-0.80). The difference in mean change between the ICI-treated group and the CT-treated group was 5.82 (95% CI, 4.11-7.53) in favour of ICI. Similarly, in the EQ-5D, the mean change differences favoured treatment with ICIs in both Utility Index and VAS, with differences of 0.05 (95% CI, 0.03-0.07) and 5.41 (95% CI, 3.39-7.43), respectively.

CONCLUSIONS

ICIs are associated with higher levels of quality of life and longer time to clinical deterioration on several PROs scales compared with CT in different types of solid tumours.

摘要

背景

免疫检查点抑制剂(ICIs)在过去几年中彻底改变了肿瘤学的临床实践,使几种肿瘤类型的患者生存获益。为了探究这些获益是否与生活质量的改善有关,我们进行了一项系统评价和荟萃分析,比较了晚期实体瘤患者中,ICI 与标准化疗(CT)相比的患者报告结局(PROs)。

方法

纳入比较 ICI(包括程序性死亡受体-1 和程序性死亡配体 1 抑制剂或细胞毒性 T 淋巴细胞相关抗原 4 抑制剂,单药或联合用药)与 CT 疗效的临床试验。还纳入了评估 ICI 联合 CT 与 CT 单独治疗效果的试验,但排除了对照组采用其他抗癌药物(如靶向治疗和其他 ICI)或安慰剂的研究。我们的荟萃分析旨在比较接受 ICI 或 ICI 联合 CT(干预)治疗的患者的 PROs 与接受 CT 治疗的患者报告的 PROs(对照)。主要终点是从基线到 PRO 首次恶化的时间,定义为从基线到 PRO 首次出现临床显著恶化的时间,以及 ICI 和 CT 治疗组之间从基线到随访的 PROs 变化(PROSPERO 注册号 CRD42021247440)。

结果

共有来自 17 项 ICI 与 CT 比较的随机试验的 8341 名患者纳入分析。与标准 CT 相比,ICI 治疗延迟了 EORTC QLQ-C30 全球健康状况/生活质量(HR 0.81;95%置信区间 [CI],0.74-0.89)以及 EQ-5D 效用指数(HR 0.65;95% CI,0.52-0.82)和 EQ-5D 视觉模拟量表(VAS;HR 0.70;95% CI,0.61-0.80)的临床恶化。ICI 治疗组和 CT 治疗组之间的平均变化差异有利于 ICI,为 5.82(95% CI,4.11-7.53)。同样,在 EQ-5D 中,效用指数和 VAS 的平均变化差异均有利于 ICI 治疗,差异分别为 0.05(95% CI,0.03-0.07)和 5.41(95% CI,3.39-7.43)。

结论

与 CT 相比,ICI 在不同类型的实体瘤中与多种 PROs 评分的更高生活质量水平和更长的临床恶化时间相关。

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