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

比较原发灶和转移灶相关PD-L1表达在预测接受免疫检查点抑制剂治疗的晚期非小细胞肺癌患者的客观缓解率中的作用

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Abstract

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSION: 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.

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