A comparative study of PD-L1 diagnostic assays in squamous cell carcinoma of the head and neck (SCCHN)

Abstract

Background: PD-1/PD-L1 directed antibodies are emerging as effective therapeutics in multiple oncology settings. In the SCCHN Checkmate 141 study, improved efficacy with nivolumab, a PD-1 targeted therapy, was observed in pts with tumour PD-L1 expression ≥1% vs pts with PD-L1 expression below this cut off. Multiple diagnostic PD-L1 tests are available using different antibody clones, different staining protocols and different cut offs. A better understanding of the technical performance of these assays will allow appropriate interpretation of clinical outcomes with different drugs. Methods: 108 tumour biopsy samples from stage I-IV SCCHN pts, obtained from a commercial source and including HPV positive and HPV negative, were assessed using 3 PD-L1 diagnostic assays: the Ventana SP263 assay currently being used in durvalumab (anti-PD-L1) clinical trials, the Dako 28-8 and Dako 22C3 assays, commonly used in nivolumab (Opdivo®) and pembrolizumab (Keytruda®) trials, respectively. Assays were performed in an accredited laboratory, following the device protocol. Concordance between tumour membrane staining was assessed across a range of clinically relevant cut offs, including ≥1%, ≥10% and ≥25%. Lower 95% CI were calculated using the Clopper-Pearson method. Results: Data indicated strong association, with a Spearman correlation coefficient of ≥0.9 for each pairwise comparison. Overall percent agreement (OPA) of >90% was seen between the three assays across multiple clinically relevant cut points. Assessment of a further 392 samples is ongoing to complement the current data set with a larger dynamic range of PD-L1 expression. Conclusions: This study indicates that the SCCHN patient population defined by Ventana SP263, Dako 28-8 and Dako 22C3 assays is similar where an identical cut point is used. The findings align with those of a similar study in NSCLC, and build optimism that it may be possible to compare studies using different PD-L1 tests and deliver harmonization of PD-L1 diagnostic testing.(Table Presented).