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<p>PD-L1 expression is an important biomarker for the management of non-small cell lung cancer (NSCLC) but has been highly heterogeneous across studies. We developed a statistical model to reconcile conflicting estimates of PD-L1 prevalence by accounting for between-study variation in test sensitivity, specimen age, and laboratory count. In doing so, we obtained refined estimates for PD-L1 expression prevalence and identified differences by histological subtype, mutational status, and stage. Across 92 studies published between 2015 and 2023, the detectability of PD-L1 declined with increasing specimen age while the consistency of detection rates was greater for studies incorporating data from a higher number of laboratories. Using the 22C3 antibody as a benchmark, we predicted that 58.3% (95% CrI 49.8–66.1%) and 27.0% (95% CrI 21.2–33.1%) of NSCLC will have PD-L1 tumour proportion scores at the ≥ 1% and ≥ 50% threshold. PD-L1 expression was lower in <i>EGFR</i>-mutated NSCLC and higher in NSCLC with <i>ALK</i>, <i>KRAS</i>, <i>MET</i>, <i>ROS1</i>, and <i>RET</i> alterations. PD-L1 expression was more common with later-stage disease. Overall, this work highlights the continuing challenge of consistency in PD-L1 testing. Although the underlying prevalence of PD-L1 expression varies in the lung cancer population based on tumour-related factors, controllable differences in testing parameters also account for variations in PD-L1 prevalence.</p>

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Why PD-L1 expression varies between studies of lung cancer: results from a Bayesian meta-analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月4日

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  • Preston Ngo,
  • Wendy A. Cooper,
  • Stephen Wade,
  • Kwun M. Fong,
  • Karen Canfell,
  • Deme Karikios,
  • Marianne Weber

摘要

PD-L1 expression is an important biomarker for the management of non-small cell lung cancer (NSCLC) but has been highly heterogeneous across studies. We developed a statistical model to reconcile conflicting estimates of PD-L1 prevalence by accounting for between-study variation in test sensitivity, specimen age, and laboratory count. In doing so, we obtained refined estimates for PD-L1 expression prevalence and identified differences by histological subtype, mutational status, and stage. Across 92 studies published between 2015 and 2023, the detectability of PD-L1 declined with increasing specimen age while the consistency of detection rates was greater for studies incorporating data from a higher number of laboratories. Using the 22C3 antibody as a benchmark, we predicted that 58.3% (95% CrI 49.8–66.1%) and 27.0% (95% CrI 21.2–33.1%) of NSCLC will have PD-L1 tumour proportion scores at the ≥ 1% and ≥ 50% threshold. PD-L1 expression was lower in EGFR-mutated NSCLC and higher in NSCLC with ALK, KRAS, MET, ROS1, and RET alterations. PD-L1 expression was more common with later-stage disease. Overall, this work highlights the continuing challenge of consistency in PD-L1 testing. Although the underlying prevalence of PD-L1 expression varies in the lung cancer population based on tumour-related factors, controllable differences in testing parameters also account for variations in PD-L1 prevalence.