Gupta Kush, Roy Arya Mariam, Attwood Kristopher, Nipp Ryan David, Mukherjee Sarbajit
Department of Internal Medicine, University of Massachusetts Chan Medical School-Baystate, Springfield, MA 01109, USA.
Department of Hematology and Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA.
Healthcare (Basel). 2024 Jul 28;12(15):1496. doi: 10.3390/healthcare12151496.
Immune checkpoint inhibitors (ICIs) have revolutionized cancer care, with increasing data demonstrating improved survival outcomes using ICIs among patients with advanced gastroesophageal cancer (GEC). ICIs are also associated with a lower incidence of grade ≥ 3 adverse events (AEs) compared to chemotherapy, suggesting that ICIs may have favorable effects on health-related quality of life (HRQoL). This meta-analysis sought to evaluate the effects of ICIs on the HRQoL of patients with advanced GEC.
We conducted an online bibliographic search on Medline via PubMed using MeSH-based terms to retrieve randomized controlled trials (RCTs) that evaluated the effects of ICIs on HRQoL in patients with advanced GEC (we searched for all studies between 2018 and 2021). We included RCTs that incorporated ICIs as part of the intervention arm either as monotherapy (first or second line) or as a combination therapy (first-line) with another ICI or chemotherapy. We combined the HRQoL measures into a meta-analysis using standard random effects models, from which estimates of the average mean difference (MD) were obtained with 95% confidence intervals. We assessed the heterogeneity of the study outcomes using the Q and I statistics.
We identified 11 phase 3 RCTs that met the inclusion criteria, with a mean enrollment of 820 patients. Eight RCTs used an ICI plus chemotherapy combination in the intervention arm, three had ICIs as monotherapy, and one had doublet ICI therapy in the intervention arm. All RCTs used chemotherapy for the control arm. Collectively, the trials reported 37 HRQoL measures using five different HRQoL tools. The pooled analysis favored the intervention over the control arm in terms of the Functional Assessment of Cancer Therapy-Esophageal (FACT-E) scores [MD 2.7 (95% CI 0.1 to 5.3), < 0.041]. In a subgroup analysis of eight RCTs comparing combination therapy with ICIs plus chemotherapy versus chemotherapy alone, the effect estimates favored the ICI arm regarding the FACT-E [MD 2.7 (95% CI 0.1 to 5.3), < 0.041] and the EORTC QLQ-OES18 pain scale [MD -2.2 (95% CI -4.3 to -0.2), < 0.030]. Likewise, the effect estimates favored the ICI monotherapy arm over the chemotherapy arm regarding the QLQ-STO22 hair loss subscale [MD -23.2 (95% CI -29.7 to -16.7), < 0.001], QLQ-STO22 dysphagia subscale [MD 6.7 (95% CI 1.7 to 11.7), = 0.009], EQ-5D pain scale [MD 6.9 (95% CI 2.9 to 10.9), < 0.001], and QLQ-OES18 saliva subscale [MD 5.8 (95% CI 0.1 to 11.6), = 0.046].
In this meta-analysis, we found that the inclusion of ICIs as a first-line treatment for advanced GEC yielded better HRQoL outcomes than chemotherapy alone. Further research on the impact of ICIs on HRQoL is needed, with increasing evidence that ICIs improve the survival outcomes in patients with advanced GEC.
免疫检查点抑制剂（ICIs）彻底改变了癌症治疗模式，越来越多的数据表明，晚期胃食管癌（GEC）患者使用ICIs可改善生存结局。与化疗相比，ICIs≥3级不良事件（AEs）的发生率也较低，这表明ICIs可能对健康相关生活质量（HRQoL）有积极影响。本荟萃分析旨在评估ICIs对晚期GEC患者HRQoL的影响。
我们通过PubMed在Medline上进行了在线文献检索，使用基于医学主题词表（MeSH）的术语检索评估ICIs对晚期GEC患者HRQoL影响的随机对照试验（RCTs）（我们检索了2018年至2021年间的所有研究）。我们纳入了将ICIs作为干预组一部分的RCTs，ICIs作为单一疗法（一线或二线）或与另一种ICIs或化疗联合使用的联合疗法（一线）。我们使用标准随机效应模型将HRQoL测量结果合并为荟萃分析，从中获得平均平均差（MD）的估计值及95%置信区间。我们使用Q和I统计量评估研究结果的异质性。
我们确定了11项符合纳入标准的3期RCTs，平均入组820例患者。8项RCTs在干预组使用ICIs加化疗联合方案，3项将ICIs作为单一疗法，1项在干预组使用双联ICI疗法。所有RCTs在对照组使用化疗。总体而言，这些试验使用五种不同的HRQoL工具报告了37项HRQoL测量结果。在癌症治疗功能评估-食管（FACT-E）评分方面，汇总分析显示干预组优于对照组[MD 2.7（95%CI 0.1至5.3），<0.041]。在八项比较ICIs加化疗联合疗法与单纯化疗的RCTs亚组分析中，关于FACT-E[MD 2.7（95%CI 0.1至5.3），<0.041]和欧洲癌症研究与治疗组织QLQ-OES18疼痛量表[MD -2.2（95%CI -4.3至-0.2），<0.030]，效应估计值有利于ICI组。同样，在QLQ-STO22脱发子量表[MD -23.2（95%CI -29.7至-16.7），<0.001]、QLQ-STO22吞咽困难子量表[MD 6.7（95%CI 1.7至11.7），=0.009]、EQ-5D疼痛量表[MD 6.9（95%CI 2.9至10.9），<0.001]和QLQ-OES18唾液子量表[MD 5.8（95%CI 0.1至11.6），=0.046]方面，效应估计值有利于ICI单一疗法组而非化疗组。
在本荟萃分析中，我们发现将ICIs作为晚期GEC的一线治疗方法比单纯化疗产生更好的HRQoL结局。需要进一步研究ICIs对HRQoL的影响，越来越多的证据表明ICIs可改善晚期GEC患者的生存结局。
