PD-L1, PD-1, and CTLA-4 as Prognostic Biomarkers in Resected NSCLC

Conference Correspondent - ASCO 2015 - Lung Cancer

Immune checkpoint inhibitors have become established as therapy for certain subsets of patients with NSCLC. However, development of reliable predictive or prognostic biomarkers is critical for successful incorporation of immune checkpoint inhibitors into lung cancer management. In a presentation by Owonikoko and colleagues,a the prognostic relevance of immune checkpoint mediators in resected NSCLC was assessed. PD-L1 expression was determined by immunohistochemistry using the authors’ institutional tumor bank samples. Mutations, expression and copy number variations (CNV) in genes encoding for PD1, PD-L1 and CTLA-4 were assessed using the Cancer Genome Atlas (TCGA) data. The prognostic impact of genetic alterations was assessed in the overall population and in subsets of adenocarcinoma, squamous cell carcinoma, smokers and non-smokers. A total of 208 institutional NSCLC samples were used in the study (199 Caucasian, 9 African Americans; male/female 101/107; squamous 63, nonsquamous 138) plus 763 NSCLC cases from the TCGA database. PD-L1 protein expression was higher in smokers, nonsquamous cancers and females but not significantly different by race, tumor stage or grade. Low PD-L1 immunoscore in cancer cells (< 10 vs ? 10, < 35 vs ? 35, or < 50 vs ? 50) and in adjacent normal tissue (0 vs > 0, < 10 vs ? 10, or < 2 vs ? 2) was significantly associated with a higher risk of recurrence and poor overall survival (OS). High tumor PD-L1 staining was also associated with higher risk of recurrence and poorer OS. Mutations in CTLA4, PD-1 and PD-L1 genes were very rare. There was no association of CTLA-4 or PD-L1 gene expression differences or CNV with survival in patients groups defined by histology or smoking status. A higher normalized PD-1 gene expression was associated with higher median OS (3.8 [1.8, 6.6] vs 1.6 [0.5, 5.4] years; P = 0.022). This study showed that PD-L1 protein expression is higher in females, in nonsquamous NSCLC, and in smokers. Importantly, PD-L1 protein expression, but not PD-L1 gene expression, may be a useful prognostic marker in resectable, early-stage NSCLC.

  1. Owonikoko TK, et al. ASCO 2015. Abstract 7551.