Combined positive score using 28-8 predicts nivolumab efficacy in HNSCC

The predictive value of programmed death-ligand 1 (PD-L1) expression for nivolumab efficacy in head and neck squamous cell carcinoma (HNSCC) remains controversial, partly due to variability among antibody clones. This study compared the SP142 and 28-8 PD-L1 antibody clones using multiple scoring systems to identify the most informative parameters for predicting nivolumab efficacy.

We retrospectively analyzed 26 patients with recurrent or metastatic HNSCC treated with nivolumab. PD-L1 expression was evaluated using SP142 and 28-8 antibody clones and quantified by four scoring systems: tumor proportion score (TPS), combined positive score (CPS), tumor cell (TC) score, and immune cell (IC) score. Associations between PD-L1 indices and clinical outcomes, including progression-free survival (PFS) and overall survival (OS), were assessed.

The SP142 clone yielded lower tumor-associated PD-L1 scores (TPS and TC score) and higher immune cell-associated scores (IC score) compared with the 28-8 clone. None of the PD-L1 parameters assessed using SP142 were significantly associated with PFS or OS. In contrast, the 28-8 clone demonstrated clear predictive value: CPS assessed with 28-8 was significantly associated with both improved PFS and OS, while TPS and TC score assessed with 28-8 predicted PFS but not OS. These findings indicate that SP142 may underestimate tumor cell PD-L1 expression, whereas 28-8 provides a more balanced assessment of PD-L1 distribution across tumor and immune compartments.

Clone selection is critical in PD-L1 immunohistochemistry, and 28-8-based CPS appears to be a practical biomarker for guiding nivolumab treatment in this setting.

Level 5.