P2.09-19 Effect of Neoadjuvant (Radio)chemotherapy on PD-L1 Expression in Resected Non-Small Cell Lung Cancers

Abstract

Programmed cell death ligand 1 (PD-L1) expression has been established as a predictive biomarker for checkpoint-inhibitor treatment in advanced non-small-cell lung carcinomas (NSCLC). Inclusion of PD1/PD-L1 inhibitors into existing neoadjuvant regimens is currently evaluated in clinical trials. However, data on the impact of neoadjuvant regimens on tumoral PD-L1 expression is rare. We aimed to assess the PD-L1 expression in NSCLC before/after neoadjuvant treatment, including its prognostic relevance. Our single-center, retrospective study cohort comprised 131 consecutive patients with NSCLC resected after neoadjuvant therapy, diagnosed 2000-2016, including 63 available pretreatment biopsies. Tumor types comprised 59 squamous cell carcinomas (SQCC), 66 adenocarcinomas (ADC) and 7 others. The pathological slides and clinical records were reevaluated assessing tumor-size according to current IASLC-recommendations by multiplying the vital tumor percentage with the macroscopic tumor bed. Biologically matched cohorts of 60 locally advanced (pN2) primary resected ADC and 54 SQCC served as controls. PD-L1 was immunohistochemically stained using the Ventana SP263 KIT and tumoral expression was assessed on whole slides by two investigators using the increments: <1%, 1-<25%, 25-<50%, ≥50%. The results were correlated with clinico-pathological parameters. PD-L1 could be evaluated in 112 specimens after neoadjuvant chemotherapy, including 24 following neoadjuvant radiochemotherapy: 53 cases scored <1%, 31 1-<25%, 4 25-<50% and 24 ≥50%. In pre-treatment biopsies, 50/63 (79.4%) cases scored <50%, 13/63 (20.6%) ≥50%. Eight/63 (12.7%) cases were discordant regarding the clinically relevant cut-off 50%, 4 cases (2 ADC, 2 SQCC) having a higher expression and 4 cases (2 ADC, 2 SQCC) with lower expression after neoadjuvant radiochemotherapy. PD-L1 expression was significantly higher in primary resected SQCC (n=53) compared to neoadjuvantly treated SQCC (n=52, p=0.014; n=41 neoadjuvant chemotherapy only, p=0.033), with 14 cases scoring <1%, 21 1-<25%, 4 25-49% and 14≥50%. There was no significant difference regarding PD-L1 expression for the paired ADC-groups. In neoadjuvantly treated NSCLC, there was no correlation between PD-L1 expression (increments or 50% cut-off) and ypT, ypN, UICC/AJCC-stage, histological tumor regression, tumor size or the size of the tumor bed. PD-L1 expression was not associated with overall survival nor progression free survival in any cohort. We document a discordance of 12.7% regarding the cut-off 50% between pre-treatment biopsies and resections after neoadjuvant therapy, which may be due to tumor-heterogeneity. The higher PD-L1 expression in primary resected SQCC compared to SQCC resected after treatment provides evidence that the influence of neoadjuvant therapy on PD-L1 expression might depend on the histological tumor type.