Abstract 2004: Comparison of PD-L1 expression in primary and metastatic lung cancer biopsies
Authors: Prince Emily A. , Chizhevsky Vladislav , Ragheb Josette William , Pratt James L. , Pandya Dimple , Huron David 
Published: September 2020

Abstract
Background: Programmed death-1/programmed death ligand 1 (PD-1/PD-L1) inhibitors are approved in a range of tumor types, including non-small cell lung cancer, with PD-L1 immunohistochemistry (IHC) diagnostic assays approved to inform treatment in some settings. There is evidence that PD-L1 expression can vary between primary tumors and metastatic sites, but the relationship remains unclear. In this real-world study, we compared PD-L1 expression between matched primary tumor and metastatic site biopsies in patients with lung cancer.
Methods: NeoGenomics Laboratories Inc (Fort Myers, FL), a US national reference laboratory, provided results for PD-L1 tests performed on samples from 21,224 patients with lung cancer between Oct 2015 and Mar 2018. Test results were linked to clinical characteristics provided by Symphony Healthcare Solutions using unique identifiers. PD-L1 tests were performed using the Dako PD-L1 IHC 28-8 or 22C3 pharmDx assays according to the manufacturers' protocols at the time. The percentage of tumor cells (TCs) expressing PD-L1 was determined by trained pathologists. Patients were included in the analysis if they had matched biopsies from a primary lung tumor and a metastatic site that were collected in any order within a 3-month period, and if both samples were tested with the same PD-L1 assay ≤ 3 months apart. Patients were excluded if they received treatment between biopsies or had &gt; 2 biopsies. Statistical analysis was performed by BioStat Solutions Inc.
Results: In total, 121 patients had matched primary and metastatic biopsy samples, with sites biopsied in any order; a subgroup of 59 patients had their second biopsy obtained after the PD-L1 test result for the first biopsy was reported. Matched biopsy pairs showed modest concordance (Kendall's tau 0.43 [95% CI, 0.33–0.54]; Spearman's correlation 0.56 [95% CI, 0.42–0.67]). Overall percentage agreement was 69–80% (Cohen's kappa 0.34–0.53) across a range of PD-L1 expression cutoffs (1%, 5%, 10%, 25%, and 50% of TCs). Identical PD-L1 expression was observed in 26% of matched biopsy pairs; 44% of sample pairs had a &lt; 5% difference and 35% of sample pairs had a &gt; 20% difference in PD-L1 expression scores between primary and metastatic sites. PD-L1 expression in primary tumor and metastatic sites was heterogeneous, with no clear trends across biopsy sites. In the subgroup of 59 patients whose second biopsy was obtained after the test result for their first biopsy was reported, 50% of patients (15/30) with PD-L1 expression on &lt; 1% of TCs in their first biopsy had PD-L1 expression on ≥ 1% of TCs in their second biopsy.
Conclusion: This real-world study suggests that agreement of PD-L1 expression between matched primary and metastatic biopsy sites is low, further highlighting PD-L1 expression heterogeneity in lung cancer. Variation in PD-L1 expression between biopsy sites may affect treatment decisions relating to PD-1/PD-L1 inhibitors.
Citation Format: Emily A. Prince, Vladislav Chizhevsky, Josette William Ragheb, James L. Pratt, Dimple Pandya, David Huron. Comparison of PD-L1 expression in primary and metastatic lung cancer biopsies [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2004.