Predictive Value of Combined Positive Score and Tumor Proportion Score for Immunotherapy Response in Advanced NSCLC

INTRODUCTION: In advanced-stage NSCLC, tumor proportion score (TPS) is typically used to predict the efficacy of immune checkpoint inhibitors (ICIs). Nevertheless, in other cancer types, the combined positive score (CPS), which covers programmed death-ligand 1 (PD-L1) expression on both tumor and surrounding immune cells, is used. We investigated the predictive value of CPS in comparison to TPS in advanced NSCLC. METHODS: A monocenter, retrospective study was performed in patients with advanced NSCLC treated with ICI monotherapy between 2015 and 2021. Hematoxylin and eosin and PD-L1 were stained on baseline tumor biopsy samples to score PD-L1 by both TPS and CPS. Positivity for TPS and CPS was defined as a score of 1% or above. Progression-free survival and overall survival (OS) were assessed for TPS and CPS scores. RESULTS: Among the 187 included patients, PD-L1 positivity was found in 112 patients (59.9%) by TPS and 135 patients (72.2%) by CPS. There was no significant difference in OS between TPS(−) and TPS(+) patients (p = 0.20). Nevertheless, CPS(+) patients did have a longer OS than CPS(−) patients (p = 0.006). OS was superior in both TPS(−)/CPS(+) and TPS(+)/CPS(+) as compared with TPS(−)/CPS(−) cases (p = 0.018 and p = 0.015, respectively), whereas no considerable differences in OS were found between TPS(−)/CPS(+) and TPS(+)/CPS(+) cases. CONCLUSIONS: This retrospective real-world population study revealed that CPS differentiated OS better than TPS in patients with advanced NSCLC with ICI monotherapy. Remarkably, this was driven by the performance of the TPS(−)/CPS(+) subgroup, indicating that CPS may be a better predictive biomarker for ICI efficacy.