Immune checkpoint inhibitors versus chemotherapy as second-line therapy for advanced oesophageal squamous cell carcinoma: a systematic review and economic evaluation
发布日期：2024-04-29
阅读次数：
摘要：Background: Recently, several novel programmed cell death protein 1 (PD-1) inhibitors have been approved for second-line treating advanced or metastatic oesophageal squamous cell carcinoma (OSCC), including camrelizumab, nivolumab, pembrolizumab, sintilimab and tislelizumab. However, the optimal treatment regimen remained ambiguous. Objectives: The purpose of this study was to investigate the efficacy, safety and economy of available PD-1 inhibitors to determine the optimal treatment from the Chinese healthcare system perspective. Design: A systematic review and economic evaluation. Data sources and methods: A systematic review was undertaken utilizing PubMed, Web of Science, Cochrane Library, Embase and Scopus databases to identify eligible studies until 31 August 2023. Primary outcomes were progression-free survival (PFS), overall survival (OS) and adverse events (AEs). We also developed a partitioned survival model at 3-week intervals based on five clinical trials to predict long-term costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios for various treatment options. Direct medical costs and utility values were obtained from public drug bidding databases, clinical trials or published literature. The parameter uncertainties within the model were determined via one-way and probabilistic sensitivity analyses. Results: Five randomized controlled trials involving 2837 patients were included in the analysis. Compared with other treatments examined, camrelizumab provided the best PFS benefits [hazard ratio (HR): 0.69, 95% confidence interval (CI): 0.56-0.86], and pembrolizumab provided the best OS benefits (HR: 0.55, 95% CI: 0.37-0.82). Nivolumab caused a relatively lower incidence of treatment-related AEs (HR: 0.10, 95% CI: 0.05-0.20) and grade 3-5 AEs (HR: 0.13, 95% CI: 0.08-0.21) than other immunotherapy regimens. In the economic evaluation, average 10-year costs ranged from $5,433.86 (chemotherapy) to $50,617.95 (nivolumab) and mean QALYs ranged from 0.55 (chemotherapy) to 0.82 (camrelizumab). Pembrolizumab was eliminated because of dominance. Of the remaining strategies, when the willingness-to-pay thresholds were 1, 2 and 3 times GDP per capita in 2022, sintilimab, tislelizumab and camrelizumab were the most cost-effective treatment options, respectively. Conclusion: Sintilimab might be the optimal treatment alternative for second-line therapy of advanced OSCC in China, followed by tislelizumab and camrelizumab.
摘要中译：
（1）背景：近年来，新型程序性细胞死亡蛋白1（PD-1）抑制剂被批准二线治疗晚期或转移性食管鳞状细胞癌（OSCC），包括卡瑞利珠单抗、纳武利尤单抗、帕博利珠单抗、信迪利单抗和替雷利珠单抗。然而，《中国临床肿瘤学会食管癌诊疗指南2023》尚未明确最优的治疗方案。
（2）目的：本研究从中国卫生体系的角度评估可获得的PD-1抑制剂二线治疗晚期OSCC的有效性、安全性和经济性，以确定最优的治疗方案。
（3）设计：一项系统综述和经济学评价。
（4）数据来源和研究方法：系统检索PubMed、Web of Science、Cochrane Library、Embase和Scopus数据库来确定相关的研究，检索时间自建库至2023年8月31日。主要产出包括无进展生存期（PFS）、总生存期（OS）和不良事件（AEs）。基于5项临床试验构建3状态分区生存模型（PFS、进展疾病和死亡）来预测不同治疗方案长期的成本、质量调整生命年（QALYs）和增量成本-效果比（ICER）。直接医疗成本和健康效用值来源于公开的药品中标数据库、临床试验和已发表的文献。模型参数的不确定性通过单因素和概率敏感性分析进行评估。
（5）结果：5项临床试验包含2837名OSCC患者。与其他治疗方案相比，卡瑞利珠单抗提供了最优的PFS（风险比（HR）:0.69，95%置信区间（CI）：0.56-0.86），帕博利珠单抗提供了最优的OS（HR：0.55，95%CI：0.37-0.82）。纳武利尤单抗发生治疗相关的不良事件（OR：0.10，95%CI：0.05-0.20）和3-5级不良事件（OR：0.13，95%CI：0.08-0.21）的风险较其他免疫方案更低。经济学评价方面，各治疗方案10年成本范围为$5433.86（化疗）至$50617.96（纳武利尤单抗），QALYs范围为0.55（化疗）至0.82（卡瑞利珠单抗）。帕博利珠单抗由于绝对劣势被剔除，当意愿支付阈值分别为1、2、3倍2022年人均GDP时，信迪利单抗、替雷利珠单抗和卡瑞利珠单抗分别是最具有成本-效果的治疗方案。
（6）结论：在中国，信迪利单抗可能是OSCC二线治疗的最佳选择，其次是替雷利珠单抗和卡瑞利珠单抗。
作者：刘世贤、窦蕾、李顺平
当前位置：
