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

Emily Pei Ying Lin, Chih Yuan Hsu, Jeng Fong Chiou, Lynne Berry, Leora Horn, Paul Bunn, James Chih Hsin Yang, Pan Chyr Yang, Alex A. Adjei, Yu Shyr

研究成果: Article同行評審

1 引文 斯高帕斯(Scopus)

摘要

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.

原文English
頁(從 - 到)1365-1374
頁數10
期刊Journal of Thoracic Oncology
17
發行號12
DOIs
出版狀態Published - 2022 12月

All Science Journal Classification (ASJC) codes

  • 腫瘤科
  • 肺和呼吸系統醫學

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