P2.09-06 Expression of PD-L1 on Routine Non-Small Cell Lung Carcinoma Sections: Comparative Assessment of SP263 (Ventana) and 22C3 (DAKO pharmDx)

Abstract

Background: Programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway-targeted immunotherapy is becoming standard practice in the management of lung cancer. The expression of PD-L1protein is expected to apply to evaluate the prognosis or to predict the response to PD-1-blocking antibodies. The immunohistochemistry(IHC) assay forPD-L1, 22C3 pharmDx, has revealed that about30% of all non-small cell lung cancer (NSCLCs) express the PD-L1 with a high level. The association between PD-L1 positivity and the clinicopathological features in lung adenocarcinoma (ADC) remains unclear, however. Method: We retrospectively evaluated the PD-L1 expression in the surgically resected tumor tissues by IHC with the 22C3 assay, from 233 primary lung ADC patients. The PD-L1 tumor proportion score (TPS) was calculated as the percentage of at least 100 viable tumor cells with complete or partial membrane staining. TPS was reported in three categories (no expression, <1%; low expression, 1-49%; and high expression, 50%). Result: Of the 233 cases analyzed, the median age was 60 (range, 34-82 years), 149 (63.9%) patients were female, 167 (71.7%) patients were never-smokers, and 55 (23.6%) patients had stage Ⅲ (50) and Ⅳ (5) disease. Among them, 139 (59.7%) patients had activating EGFR mutations, and 23 (9.9%) patients were KRAS mutant. Proportions in each PD-L1 TPS category were: <1%, 63.9%(149/233); 1-49%, 23.6%(55/233); 50%, 12.5%(29/233). Wilcoxon rank sum test(Mann-Whitney U test) revealed that PD-L1 positivity had negative correlation with patient age (p ¼ 0.027), and positive correlation with male (p ¼ 0.001), smoker (p ¼ 0.007), advanced stage (p < 0.001). EGFR-mutated tumors (n¼ 139) demonstrated lower rates of PD-L1 expression [TPS <1% (72.7%); 1-49% (22.3%); 50% (5.0%); P<0.001];meanwhile, KRAS-mutated tumors (n¼ 23) showed higher rates of PD-L1 expression [TPS <1% (43.5%); 1-49% (30.4%); 50% (26.1%); P<0.001]. Conclusion: This investigation shows that in primary lung adenocarcinoma the PD-L1 expression was significantly associated with younger age, male, smokers, high stage disease, EGFR wild-type and KRAS mutant. Therefore, it is rational to choose a different checkpoint inhibitor according to the driver gene mutation status and to combine targeted therapies and anti-PD-L1 agents.Background: Four PD-L1 antibodies have been utilized in NSCLC clinical trials, with an analytical comparison demonstrating a high level of concordance between the percentage of PD-L1estained tumor cells with three of these antibodies (22C3, 22C3, 28-8, and SP263), but not a fourth, SP-142 (Hirsch et al, JTO 2017). This finding led us to evaluate the relationship between the percentage of PD-L1estained tumor cells with 22C3 and SP-142, as well as the association between the PD-L1 levels identified by each antibody and clinical outcomes in 28 NSCLC patients treated on KEYNOTE-001. Method: We performed a retrospective analysis of 28 NSCLC patients treated with pembrolizumab on the KEYNOTE-001 trial at UCLA (23pts) or MSKCC (5pts) with...