Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Mod Pathol. 2021 Sep;34(9):1719-1727. doi: 10.1038/s41379-021-00823-9. Epub 2021 May 17.
Recent clinical trials have shown the promising therapeutic effects of pembrolizumab and nivolumab in patients with advanced gastric cancer. Currently, the programmed death ligand-1 (PD-L1) 22C3 pharmDx assay is the only companion diagnostic assay for assessing the safety and effectiveness of pembrolizumab. The purpose of this study was to compare 22C3 pharmDx and 28-8 pharmDx, a complementary diagnostic assay for nivolumab, in gastric cancer. In this study, 22C3 and 28-8 pharmDx assays were performed on the same formalin-fixed, paraffin-embedded tissue blocks of gastric adenocarcinoma clinical samples (n = 55). The concordance rate was evaluated using combined positive score (CPS) cutoffs of 1, 10, and 50. PD-L1 positivity with CPS ≥ 1 was 45.5% using the 22C3 pharmDx assay and 49.1% using the 28-8 pharmDx assay. At a CPS cutoff of 1, the overall percentage agreement was 96.4%. The positive and negative percentage agreements were 93.3% and 100%, respectively. All cases positive for PD-L1 using the 22C3 pharmDx assay were also positive using the 28-8 pharmDx assay. At a CPS cutoff of 10, the overall percentage agreement was 96.4%. At a CPS cutoff of 50, the two assays exhibited 100% concordance. Nonspecific cytoplasmic staining in the background tissues and tumor cells was often observed in the 28-8 pharmDx assay. When the results of the two assays were matched for response to immunotherapy, the overall response rate was higher in patients with a PD-L1 CPS ≥ 1 than in PD-L1-negative patients (22C3 pharmDx, P = 0.001; 28-8 pharmDx, P = 0.002). In conclusion, PD-L1 22C3 and 28-8 pharmDx assays were highly comparable at CPS cutoffs of 1, 10, and 50 in gastric cancer. These results provide evidence for the potential interchangeability of the two PD-L1 assays in gastric cancer.
最近的临床试验表明，帕博利珠单抗和纳武利尤单抗在晚期胃癌患者中具有有前景的治疗效果。目前，程序性死亡配体-1（PD-L1）22C3 pharmDx 检测是评估帕博利珠单抗安全性和有效性的唯一伴随诊断检测。本研究旨在比较 PD-L1 22C3 pharmDx 和纳武利尤单抗的互补诊断检测 28-8 pharmDx 在胃癌中的应用。在这项研究中，对 55 例胃腺癌临床样本的同一块福尔马林固定、石蜡包埋组织块进行了 22C3 和 28-8 pharmDx 检测。使用联合阳性评分（CPS）截断值 1、10 和 50 来评估一致性率。使用 22C3 pharmDx 检测时，PD-L1 阳性的 CPS≥1 的比例为 45.5%，使用 28-8 pharmDx 检测时为 49.1%。在 CPS 截断值为 1 时，总百分比一致性为 96.4%。阳性和阴性百分比一致性分别为 93.3%和 100%。使用 22C3 pharmDx 检测为阳性的所有 PD-L1 病例也使用 28-8 pharmDx 检测为阳性。在 CPS 截断值为 10 时，总百分比一致性为 96.4%。在 CPS 截断值为 50 时，两种检测方法完全一致。在 28-8 pharmDx 检测中，背景组织和肿瘤细胞中经常观察到非特异性细胞质染色。当两种检测方法的结果与免疫治疗反应相匹配时，PD-L1 CPS≥1 的患者总体反应率高于 PD-L1 阴性患者（22C3 pharmDx，P=0.001；28-8 pharmDx，P=0.002）。总之，在胃癌中，PD-L1 22C3 和 28-8 pharmDx 检测在 CPS 截断值为 1、10 和 50 时高度可比。这些结果为两种 PD-L1 检测在胃癌中的潜在可互换性提供了证据。
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