Cox 比例风险比高估了免疫检查点抑制剂的生存获益：Cox-TEL 调整和程序性死亡配体 1 表达与免疫检查点抑制剂生存获益的荟萃分析。
Cox Proportional Hazard Ratios Overestimate Survival Benefit of Immune Checkpoint Inhibitors: Cox-TEL Adjustment and Meta-Analyses of Programmed Death-Ligand 1 Expression and Immune Checkpoint Inhibitor Survival Benefit.
机构信息
Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, Tennessee; Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan; Department of Medical Research, Taipei Medical University Hospital, Taipei, Taiwan.
Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, Tennessee.
出版信息
J Thorac Oncol. 2022 Dec;17(12):1365-1374. doi: 10.1016/j.jtho.2022.08.010. Epub 2022 Aug 30.
INTRODUCTION
Survival benefit of immune checkpoint inhibitor (ICI) therapy in lung cancer is not fully understood.
METHODS
PubMed-cataloged publications through February 14, 2022, were queried for randomized controlled trials of ICI in lung cancer, and identified publications were reviewed for inclusion. Reported Cox hazard ratios (HRs) for overall survival were transformed to Cox-TEL HR for ICI short-term survivors (ST-HR) and difference in proportions for patients with long-term survival (LT-DP). Meta-analyses were performed using a frequentist random-effect model. Outcomes of interest were pooled overall survival Cox HR, ST-HR, and LT-DP in NSCLC, stratified by programmed death-ligand 1 (PD-L1) level (primary outcome) and ICI treatment line (secondary).
RESULTS
A total of nine publications representing eight clinical trials were selected for meta-analysis. Primary analysis yielded the following metrics for patients with PD-L1 expression less than 1%, more than or equal to 1%, and more than or equal to 50%, respectively: pooled Cox HR, 0.71 (95% confidence interval [CI]: 0.62-0.82), 0.74 (95% CI: 0.68-0.82), and 0.62 (95% CI: 0.54-0.70); pooled ST-HR, 0.91 (95% CI: 0.79-1.05), 0.88 (95% CI: 0.82-0.94), and 0.70 (95% CI: 0.60-0.83); and pooled LT-DP, 0.10 (95% CI: 0.00-0.20), 0.09 (95% CI: 0.06-0.12), and 0.11 (95% CI: 0.05-0.17). Results of secondary analysis revealed LT-DP of approximately 10% across treatment lines.
CONCLUSIONS
This study reveals an approximately 10% long-term survival probability increment in ICI long-term survivors across PD-L1-positive subpopulations in both ICI treatment lines. Furthermore, ST-HR was consistently poorer than Cox HR. For patients with PD-L1 less than 1%, neither LT-DP nor ST-HR achieved statistical significance. The analysis provides greater insight into the treatment effect of ICI in published trials.
简介
免疫检查点抑制剂（ICI）治疗在肺癌中的生存获益尚未完全明确。
方法
通过检索截至 2022 年 2 月 14 日的 PubMed 目录出版物，查询了ICI 治疗肺癌的随机对照试验，并对入选的出版物进行了回顾性审查。报告的总体生存 Cox 风险比（HR）被转化为 ICI 短期存活者的 Cox-TEL HR（ST-HR）和长期存活者的比例差异（LT-DP）。使用频率论随机效应模型进行了荟萃分析。主要研究终点为非小细胞肺癌（NSCLC）的总体生存 Cox HR、ST-HR 和 LT-DP，按程序性死亡配体 1（PD-L1）水平（主要结局）和 ICI 治疗线（次要结局）分层。
结果
共选择了 9 项研究，涉及 8 项临床试验进行荟萃分析。主要分析结果如下：PD-L1 表达<1%、≥1%和≥50%的患者的汇总 Cox HR 分别为 0.71（95%置信区间[CI]：0.62-0.82）、0.74（95% CI：0.68-0.82）和 0.62（95% CI：0.54-0.70）；汇总 ST-HR 分别为 0.91（95% CI：0.79-1.05）、0.88（95% CI：0.82-0.94）和 0.70（95% CI：0.60-0.83）；汇总 LT-DP 分别为 0.10（95% CI：0.00-0.20）、0.09（95% CI：0.06-0.12）和 0.11（95% CI：0.05-0.17）。次要分析结果显示，各治疗线的 LT-DP 约为 10%。
结论
本研究揭示了在 ICI 治疗线的 PD-L1 阳性亚群中，ST-HR 始终劣于 Cox HR。对于 PD-L1<1%的患者，LT-DP 和 ST-HR 均未达到统计学意义。分析结果为已发表试验中 ICI 的治疗效果提供了更深入的了解。
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