Comparison of primary and metastatic site-related PD-L1 expression in predicting ORR in patients with advanced NSCLC who received ICB-based therapy.

Abstract

Whether the value of PD-L1 expression from metastatic sites to predict the efficacy of immune checkpoint blockade (ICB)-based treatment is equivalent to that from a primary tumor is uncertain. This study aimed to compare the utility of PD-L1 TPS from a primary lung tumor and metastatic sites to predict the overall response rate (ORR) of first-line ICB-based treatment. This study included 249 patients with advanced non-small cell lung cancer (NSCLC) who received first-line ICB-based treatment. All subjects underwent PD-L1 testing prior to ICB-based treatment and were divided into two cohorts corresponding to the different biopsy sites: lung primary site-sampled cohort (PT cohort, n = 167) and metastatic site-sampled cohort (MT cohort, n = 82). There was no statistical significance in PD-L1 TPS distribution between the two cohorts (p = 0.742). PD-L1 TPS ≥50% was also related to high ORR compared with PD-L1 < 50% in the PT cohort (34.3% vs. 14.1%, p = 0.004). In contrast, ICB-based therapy could bring comparable ORR (35.1% vs. 33.3%, p = 0.871) in the MT cohort regardless of PD-L1 TPS status (≥50%, or <50%). As supported, when the cutoff value of TPS was selected as 50%, it was suggested that PT-related PD-L1 was the independent predictor of ORR (OR 2.870, 95% CI: 1.231-6.694, p = 0.015) rather than MT-related PD-L1 (OR 0.689, 95% CI: 0.236-2.013, p = 0.495). Furthermore, ROC proved that PT-related PD-L1 expression manifested a better AUC of 0.621 (p = 0.026) than that of MT-related PD-L1 (AUC = 0.565, p = 0.362). Compared with PT-related PD-L1 expression, MT-related PD-L1 expression showed limited value in predicting ORR in patients with advanced NSCLC receiving ICB-based therapy. It was concluded that even patients with low MT-related PD-L1 expression could benefit from ICB-based therapy.