Companion Diagnostics, Merck & Co., Inc., Kenilworth, NJ, USA.
Health Economics and Outcomes Research, Merck & Co., Inc., Kenilworth, NJ, USA.
Mod Pathol. 2021 Mar;34(3):532-541. doi: 10.1038/s41379-020-00710-9. Epub 2020 Nov 25.
Tumor proportion score (TPS) and combined positive score ([CPS] includes immune cells), 2 methods for scoring programmed death ligand 1 (PD-L1) expression, have been used in clinical trials investigating the immune checkpoint inhibitor pembrolizumab in head and neck squamous cell carcinoma (HNSCC). These trials resulted in regulatory approval for pembrolizumab in the first- and second-line setting outside the United States. We performed a post hoc analysis of the KEYNOTE-040 study (NCT02252042) to determine whether CPS is a practical and suitable alternative scoring method to TPS. In KEYNOTE-040, patients with metastatic HNSCC received pembrolizumab or investigator choice of standard of care (SOC). The relative utility and equivalence of CPS ≥ 50 and TPS ≥ 50% for defining PD-L1 expression status in patients with HNSCC and comparability of scoring methods by tandem receiver operating characteristic (ROC) analysis were analyzed. The cutoff for each method was also evaluated. CPS ≥ 50 appeared equivalent to TPS ≥ 50% for predicting objective response rate (ORR), overall survival, and progression-free survival. ORR for pembrolizumab versus SOC was 26.2 versus 8.5% for TPS ≥ 50%, 28.1 versus 7.7% for CPS ≥ 50, 10.6 versus 11.6% for TPS < 50%, and 10.0 versus 12.0% for CPS < 50. Tandem ROC analysis showed that TPS 50% and CPS 50 maximized delta Youden index and suggested that CPS is more sensitive than TPS at lower cutoffs (i.e., CPS ≥ 1). In conclusion, CPS 50 can be used interchangeably with TPS 50% to determine PD-L1 status in patients with HNSCC. CPS may be more sensitive than TPS at lower cutoffs.
肿瘤比例评分（TPS）和联合阳性评分（[CPS]包括免疫细胞）是用于评估程序性死亡配体 1（PD-L1）表达的 2 种评分方法，已用于评估免疫检查点抑制剂 pembrolizumab 在头颈部鳞状细胞癌（HNSCC）中的临床试验。这些试验导致在美国以外的一线和二线治疗环境中监管机构批准 pembrolizumab。我们对头颈部鳞状细胞癌患者接受 pembrolizumab 或研究者选择的标准护理（SOC）治疗的 KEYNOTE-040 研究（NCT02252042）进行了事后分析，以确定 CPS 是否是 TPS 的一种实用且合适的替代评分方法。在 KEYNOTE-040 中，转移性 HNSCC 患者接受 pembrolizumab 或研究者选择的 SOC 治疗。分析 CPS≥50 和 TPS≥50%用于定义 HNSCC 患者 PD-L1 表达状态的相对效用和等效性，以及通过串联接受者操作特征（ROC）分析比较评分方法的可比性。还评估了每种方法的截止值。CPS≥50 似乎与 TPS≥50%等效，可预测客观缓解率（ORR）、总生存期和无进展生存期。对于 TPS≥50%，pembrolizumab 与 SOC 的 ORR 为 26.2%比 8.5%，CPS≥50 为 28.1%比 7.7%，TPS<50%为 10.6%比 11.6%，CPS<50%为 10.0%比 12.0%。串联 ROC 分析表明，TPS 50%和 CPS 50%最大限度地提高了 delta Youden 指数，并表明 CPS 在较低的截止值（即 CPS≥1）下比 TPS 更敏感。总之，CPS 50 可以与 TPS 50%互换使用，以确定 HNSCC 患者的 PD-L1 状态。CPS 在较低的截止值下可能比 TPS 更敏感。
