Department of Pathology and Laboratory Medicine, King Hussein Cancer Center, Amman, Jordan.
Appl Immunohistochem Mol Morphol. 2021 Jul 1;29(6):462-466. doi: 10.1097/PAI.0000000000000902.
The immune checkpoint inhibitor Pembrolizumab has been FDA-approved for the treatment of gastric cancer (GC) and gastroesophageal junction (GEJ) cancer in patients who fail second-line therapy and test positive by a companion programed death ligand 1 (PD-L1) assay, the 22C3 PharmDx. It would be useful to investigate the potential interchangeability of other PD-L1 assays in order to develop a more sustainable diagnostic strategy. We investigated the possibility of harmonizing different PD-L1 assays, utilizing samples from 94 GC and GEJ patients to compare their expression using 2 laboratory developed tests (LDTs): The Dako 22C3 antibody and the Ventana SP263 run on the Ventana platform with the FDA-approved companion diagnostic test, the 22C3 PharmDx. This would be the first report assessing the 22C3 on Ventana's platform in GC. Pearson correlation coefficients between the Dako 22C3 PharmDx and the 22C3-LDT and the Ventana SP263 assays were 0.965 (P<0.001) and 0.932 (P<0.001), respectively, which indicates an almost perfect correlation. The sensitivity and specificity were also high at different cutoffs [both 100% at combined positive score (CPS)≥1 and 92.59% and 95.52% at CPS≥10, respectively] for the comparison between Dako 22C3/22C3-LDT assays. As for the sensitivity and specificity between the Dako 22C3/Ventana SP263 assays the results were 100% and 95.67% at CPS≥1; and 96.30% and 95.52% at CPS≥10, respectively. In conclusion, the analytical performance of 22C3 and SP263 clones on the Ventana platform was close to that of the reference assay (Dako 22C3 assay), suggesting that the 2 LDTs can be utilized interchangeably with the FDA-approved standard assay as an aid to select GC and GEJ patients for Pembrolizumab treatment.
免疫检查点抑制剂 Pembrolizumab 已获美国食品药品监督管理局批准，用于二线治疗失败且经伴随程序死亡配体 1（PD-L1）检测（22C3 PharmDx）阳性的胃癌（GC）和胃食管交界处（GEJ）癌患者的治疗。研究其他 PD-L1 检测方法的潜在可互换性，以制定更可持续的诊断策略将是很有用的。我们利用 94 例 GC 和 GEJ 患者的样本，研究了不同 PD-L1 检测方法的协调可能性，比较了使用 2 种实验室开发的检测方法（LDT）的表达情况：Dako 22C3 抗体和在 Ventana 平台上运行的 Ventana SP263，同时使用经美国食品药品监督管理局批准的伴随诊断检测，22C3 PharmDx。这将是评估 GC 中 Ventana 平台上的 22C3 的第一份报告。Dako 22C3 PharmDx 与 22C3-LDT 和 Ventana SP263 检测之间的 Pearson 相关系数分别为 0.965（P<0.001）和 0.932（P<0.001），这表明存在几乎完美的相关性。在不同的截止值下，灵敏度和特异性也很高[Dako 22C3/22C3-LDT 检测的组合阳性评分（CPS）≥1时均为 100%，CPS≥10 时分别为 92.59%和 95.52%]。对于 Dako 22C3/Ventana SP263 检测之间的灵敏度和特异性，结果分别为 CPS≥1 时为 100%和 95.67%；CPS≥10 时为 96.30%和 95.52%。总之，22C3 和 SP263 克隆在 Ventana 平台上的分析性能接近参考检测（Dako 22C3 检测），这表明这 2 种 LDT 可以与经美国食品药品监督管理局批准的标准检测互换使用，作为选择 GC 和 GEJ 患者接受 Pembrolizumab 治疗的辅助手段。
