A retrospective evaluation of PD-L1 expression on primary non-small cell lung cancer (NSCLC) samples and associated involved hilar or mediastinal lymph nodes (N1 or N2) (REPLICA).

Abstract

9044 Background: Little is known about the PD-L1 expression in early stage NSCLC as well as the possible heterogeneity of PD-L1 expression in different sites. This study provides information on both PD-L1 expression in stage II and III NSCLC and the relationship between PD-L1 expression in the primary site (lung) and metastatic lymph nodes (LNs) N1 and/or N2. Methods: Samples (primary tumor and N1/N2) from 500 patients who underwent lung resection and lymphadenectomy for NSCLC without prior treatments were collected and analyzed for PD-L1 expression using the 22C3 pharmdx Agilent assay. The tumor proportion score (TPS) is documented for each sample according to the following categories: PD-L1: < 1%, 1-49%, ≥ 50%. PD-L1 stained slides were reviewed by two pathologists independently; for discrepant cases the two pathologists reviewed the stains jointly and the consensus score used for the data analysis. Agreement between the two pathologists was assessed by overall agreement and kappa statistic. The association between PD-L1 expression in the primary tumor and lymph node was assessed by cross-tabulation. Results: A total of 456 tumors and involved LNs were included in the analysis. Pathologist one assessed 435 primary tumor and LN pairs and pathologist 2 assessed 453 tumor and LNs pairs. The overall agreement between pathologists on PD-L1 expression in primary tumor samples was 77%; K = 0.59 (95% CI 0.57 – 0.63) and in LNs 83%; k = 0.62 (95% CI 0.56 – 0.70). Primary tumors showed PD-L1 < 1% in 235/422 (55,6%), PD-L1 1-49% in 146/422 (34,6%) and PD-L1 > = 50% in 41/422 (9.8%). 77% (327/422) showed no heterogeneity in PD-L1 expression between the primary tumor and involved LNs. In tumors with PD-L1 < 1% expression, 94% of the LNs showed PD-L1 < 1% expression and less than 1% showed PD-L1 > = 50%, 6% of the LNs showed PD-L1 1-49%. When the primary tumor was PD-L1 > = 50% nearly half (46%) of the involved LNs showed the same degree of PD-L1 positivity and 10% of them showed PD-L1 < 1%; 44% of the LNs showed PD-L1 1-49%. When the primary tumor showed 1-49% PD-L1 staining, 60% of the LNs showed the same staining pattern, 36% showed PD-L1 < 1% and only 4% showed PD-L1 > = 50% expression. Conclusions: In stage II and III NSCLC, half of the primary tumors show negative PD-L1 expression. Discrepant PD-L1 expression between primary tumors and LN metastases was seen in 23% of the cases, and when present, PD-L1 expression in LN tumors tended to be lower than that in primary tumors.