Time is up for PD-L1 testing standardization in lung cancer

The treatment options for patients with advanced non-small-cell lung carcinoma have undergone major changes in the recent years, particularly after the FDA approval of PD-1/PD-L1 immune checkpoint inhibitors nivolumab, pembrolizumab and atezolizumab) [1–8]. Each PD-1/PD-L1 inhibitor was approved together with a specific PD-L1 immunohistochemistry assay used in the clinical trials. In addition to unique primary antibody, each assay is optimized for use with a different detection system (i.e. Dako Link 48 and Ventana BenchMark) and a different diagnostic kit. Furthermore, the unique scoring algorithms for immunohistochemical assays were co-developed with each immune checkpoint inhibitor based on predictive values shown in the clinical trials. The one drug–one assay approach is challenging to implement in clinical practice as most laboratories do not use all of the staining platforms and such practice leads to avoidable escalation of laboratory testing cost and health care in general. The main question is whether laboratories will make effort to implement the FDA approved predictive assays for one or more anti-PD-1/PD-L1 checkpoint inhibitors or implement one or more affordable laboratory developed tests (LDTs) using already available testing platforms. To find the answer to this question it is essential to determine analytical concordance between commercially available PD-L1 immunohistochemical assays. Several studies showed an excellent analytical concordance between either FDA approved or LDTs [9–13]. Three assays SP263, 22C3 and 28-8 showed a high concordance in percentage of PD-L1 membrane staining of tumor cells at any intensity. In contrast, lower expression of PD-L1 on tumor cells was observed with SP142 clone. In terms of interpretation, interobserver concordance was high for tumor cell PD-L1 expression, while it was low for immune cells.