Background PD-L1 22C3 IHC pharmDx (SK006) is a qualitative immunohistochemical (IHC) assay using anti-PD-L1, Clone 22C3 to detect PD-L1 in formalin-fixed, paraffin-embedded (FFPE) tumor tissues using the Autostainer Link 48. PD-L1 expression is determined by Combined Positive Score (CPS), which is the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100. 1 SK006 has been analytically validated using CPS across multiple tumor indications and diagnostic cutoffs and is used as an aid in identifying patients for treatment with KEYTRUDA ® . A previous publication presents the analytical performance of the following indications: gastric or gastroesophageal junction (GC/GEJ) adenocarcinoma (CPS ! 1), cervical cancer (CPS ! 1), head and neck squamous cell carcinoma (HNSCC) (CPS ! 1), esophageal cancer (EC/ESCC) (CPS ! 10), and triple-negative breast cancer (TNBC) (CPS ! 10). 2 This study evaluated the analytical performance of the SK006 assay for an additional five individual tumor indications (ovarian carcinoma (OC), prostate cancer (PC), colorectal carcinoma (CRC), renal cell carcinoma (RCC), biliary tract adeno cancer (BTAC)) and a group of 11 rare tumor indications in a basket trial (BT). 3 Two CPS cutoffs were evaluated: CPS ! 1 (OC, PC, CRC, RCC, BTAC and BT [3]) and CPS ! 10 (OC, CRC and BTAC). Methods Combined precision measured inter-instrument, -operator, -day and -lot variation. Intra-run measured repeatability and Inter/Intra-Observer measured scoring reproducibility. Negative percent agreement (NPA), positive percent agreement (PPA), and overall agreement (OA) with two-sided 95% bootstrap confidence intervals (CIs) were used for data analysis, based on the PD-L1 binary status at the evaluated cutoffs.
BackgroundPD-L1 IHC 22C3 pharmDx uses Tumor Proportion Score (TPS) and Combined Positive Score (CPS) scoring algorithms for the immunohistochemical (IHC) evaluation of PD-L1 protein expression in human cancer tissues; both algorithms include PD-L1 staining tumor cells (TC) in scoring and CPS also includes scoring of PD-L1 staining mononuclear inflammatory cells to aid in the identification of patients for treatment with pembrolizumab (KEYTRUDA®) using indication-specific diagnostic cut-offs. This study evaluated contribution of TC in determining specimen diagnostic status based on the CPS scoring algorithm by looking into four tumor indications approved for use with KEYTRUDA®: gastric or gastroesophageal junction (GEJ) adenocarcinoma (GC/GEJ), urothelial carcinoma (UC), head and neck squamous cell carcinoma (HNSCC), and esophageal squamous cell carcinoma (ESCC). Detection of specimens expressing PD-L1 is significantly dependent on the PD-L1 staining TC component.MethodsA retrospective analysis was done looking at Dako’s internal tumor bank of the mentioned indications that were all stained with PD-L1 IHC 22C3 pharmDx and scored using the TPS, CPS and Quantitative Immune Cell Density (QID) methods described in figure 1. Statistical analysis encompassed looking at the scores generated that met the following criteria: CPS>0, TPS>0 and CPS≠TPS and then evaluating the percentage of those samples that changed from positive to negative diagnostic status upon removal of the TC component from the scoring.ResultsA noticeable downward trend was observed in all four indications in the total number of positives with the removal of the TC component. Table 1 aptly captures this by showing the number of specimens for each indication that had changed from positive to negative around each indication’s diagnostic cut-off(s). The three indications that showed the highest percentages of diagnostic status change were HNSCC (CPS ≥20) with a remarkable 83.3% (130) followed by UC (CPS ≥10) at 46.3% (57) and ESCC (CPS ≥10) at 36.6% (45) of the specimens reclassified as negative.Abstract 81 Figure 1PD-L1 Scoring AlgorithmsThe TPS algorithm (a) is defined as the number of PD-L1 staining tumor cells divided by the total number of viable TC, multiplied by 100. The CPS algorithm (b) includes TC and IC and is defined as the number of PD-L1 staining cells (TC, lymphocytes and macrophages) divided by the total number of viable TC, multiplied by 100. In addition to TPS and CPS, QID (c) was also calculated to quantify the contribution from PD-L1 expressing IC, QID is defined as the CPS minus the TPS.Abstract 81 Table 1Agilent Tumor Bank CPS and QIDConclusionsPD-L1 IHC 22C3 pharmDx (Dako, USA) stains both TC and immune cells. Removal of the PD-L1 staining TC from the CPS algorithm reduces the number of specimens scored as positive for each indication’s respective diagnostic cut-off(s). Scoring only IC reduces the number of specimens scored as positive for each indication’s respective cutoff.
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