Abstract
The introduction of immunotherapy targeting the programmed death-1 (PD-1)/programmed death-ligand-1 (PD-L1) axis has represented a turning point in the treatment of HNSCC. Harmonization studies comparing the different antibodies and immunohistochemistry platforms available for the evaluation of PD-L1 expression with Combined Positive Score (CPS) in HNSCC are strongly required. Tissue microarrays (TMA) constructed from formalin-fixed, paraffin-embedded (FFPE) tissue blocks of HNSCC tumor were stained with two commercial in-vitro diagnostic (IVD) PD-L1 immunohistochemical assays (22C3 pharmDx on Autostainer Link48 and Omnis platforms, and SP263) and were reviewed by seven trained pathologists to assess CPS. We found a very similar distribution for PD-L1 expression between 22C3 pharmDx assay with both platforms and SP263 assay and a strong significant correlation between the two assays in different platforms (p < 0.0001). The interobserver reliability among pathologists for the continuous scores of CPS with intraclass correlation coefficient (ICC) and the correlation between the two assays were both good. Moreover, the agreement rate between assays was high at all cut-offs, while the kappa values were from substantial to almost perfect. These data suggest the interchangeability of the two antibodies and of the different immunohistochemical platforms in the selection of patients with HNSCC for immunotherapy.
Highlights
With approximately 880,000 new patients each year, head and neck squamous cell carcinoma (HNSCC) represents the sixth-most common type of cancer worldwide [1]
programmed death-ligand-1 (PD-L1) IHC was performed using the 22C3 pharmDx, on two different platforms, and the SP263 assays and the Combined Positive Score (CPS) per patient were calculated by taking the mean of all Tissue microarrays (TMA) cores (Figure 1)
When we considered the cut-off of ≥1, 37 cases (92.5%) had a positive CPS score with both 22C3 pharmaDx tests and SP263 assays
Summary
With approximately 880,000 new patients each year, head and neck squamous cell carcinoma (HNSCC) represents the sixth-most common type of cancer worldwide [1]. The subsequent KEYNOTE-048 phase 3 trial compared pembrolizumab alone or in combination with platinum and 5-fluorouracil-based chemotherapy [5] In this trial the combined positive score (CPS), considering both PD-L1-positive tumor cells and tumor-infiltrating leukocytes (TIL), was used to assess PD-L1 expression levels [5]. Pembrolizumab was approved in monotherapy for patients with CPS ≥ 1 assessed with an IHC test approved by FDA-, and in combination with platinum and fluorouracil regardless of PD-L1 status. In 2020, the European Medicines Agency (EMA) approved the use of pembrolizumab as first-line treatment for R/M HNSCC in patients with CPS ≥ 1 in monotherapy or in combination with chemotherapy, and as second-line therapy for tumors with TPS ≥ 50%, regardless of the test (antibody and IHC platform) used [7]. An increased benefit from therapy was seen in tumors with CPS ≥ 20 [5]
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