Association with PD-L1 Expression and Clinicopathological Features in 1000 Lung Cancers: A Large Single-Institution Study of Surgically Resected Lung Cancers with a High Prevalence of EGFR Mutation.

Lee Lee,Choi Choi,Sung Sung,Han Han,Kim Kim

doi:10.3390/ijms20194794

Abstract

Programmed cell death ligand 1 (PD-L1) expression is an important biomarker for predicting response to immunotherapy in clinical practice. Hence, identification and characterization of factors that predict high expression of PD-L1 in patients is critical. Various studies have reported the association of PD-L1 expression with driver genetic status in non-small cell cancer; however, the results have been conflicting and inconclusive. We analyzed the relationship between PD-L1 expression and clinicopathological factors including driver genetic alterations in 1000 resected lung cancers using a clinically validated PD-L1 immunohistochemical assay. PD-L1 expression was significantly higher in squamous cell carcinoma (SCC) compared to adenocarcinomas. PD-L1 expression in adenocarcinoma was associated with higher N-stage, solid histologic pattern, EGFR wild type, and ALK positive, but no significant association with the clinicopathological factors in SCC. EGFR mutant adenocarcinomas with distinctive clinicopathologic features, especially solid histologic pattern and higher stage showed higher PD-L1 expression. To the best of our knowledge, this study is the largest to evaluate the association between PD-L1 expression and clinicopathological and molecular features in lung cancer with a highly prevalent EGFR mutation. Therefore, our results are useful to guide the selection of lung cancer, even EGFR-mutated adenocarcinoma patients with PD-L1 expression, for further immunotherapy.

Highlights

The immune checkpoint inhibitors anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) are currently changing the approach of treatment to patients with non-small cell lung cancer (NSCLC)
In the NCCN guideline, the Food and Drug Administration (FDA)-approved 22C3 IHC assay for PD-L1 utilizes a cutoff of 50% tumor proportion score (TPS) for first-line therapy and 1% TPS for second-line therapy with pembrolizumab in NSCLC [1]
We focused on PD-L1 expression in patients with EGFR mutated lung adenocarcinomas

Summary

Introduction

The immune checkpoint inhibitors anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) (anti–PD-1/PD-L1) are currently changing the approach of treatment to patients with non-small cell lung cancer (NSCLC). Over the last two years, the U.S Food and Drug Administration (FDA) has granted approval to the anti–PD-1 inhibitors, nivolumab (OPDIVO) and pembrolizumab (KEYTRUDA) and the anti–PD-L1 inhibitor, atezolizumab (TECENTRIQ) for the treatment of patients with advanced NSCLC with progression during or after first-line therapy [1,2,3]. Identification of patients who might benefit from immune checkpoint inhibition in NSCLC is significant. In the NCCN guideline, the FDA-approved 22C3 IHC assay for PD-L1 utilizes a cutoff of 50% tumor proportion score (TPS) for first-line therapy and 1% TPS for second-line therapy with pembrolizumab in NSCLC [1]

Methods

Results

Discussion

Conclusion