PD-L1 Expression and Survival among Patients with Advanced Non–Small Cell Lung Cancer Treated with Chemotherapy

Abstract

BACKGROUND: Recent clinical trial results have suggested that programmed cell death ligand 1 (PD-L1) expression measured by immunohistochemistry may predict response to anti–programmed cell death 1 (PD-1) therapy. Results on the association between PD-L1 expression and survival among patients with advanced non–small cell lung cancer (NSCLC) treated with chemotherapy are inconsistent. MATERIAL AND METHODS: We evaluated the relationship between PD-L1 expression and overall survival (OS) among 204 patients with advanced NSCLC treated at Aarhus University Hospital, Aarhus, Denmark, from 2007 to 2012. PD-L1 expression was measured using a prototype immunohistochemistry assay with the anti–PD-L1 22C3 antibody (Merck). PD-L1 strong positivity and weak positivity were defined to be traceable to the clinical trial version of the assay. RESULTS: Twenty-five percent of patients had PD-L1 strong-positive tumors, and 50% had PD-L1 weak-positive tumors. No statistically significant association was found between PD-L1 expression and survival; adjusted hazard ratio of 1.34 (95% confidence interval, 0.88-2.03; median OS, 9.0 months) for the PD-L1 strong-positive group and 1.07 (0.74-1.55; median OS, 9.8 months) for the PD-L1 weak-positive group compared with the PD-L1–negative group (median OS, 7.5 months). No association was seen between PD-L1 expression and OS when PD-L1 expression levels were stratified by median or tertiles. CONCLUSIONS: In concordance with previous studies, we found PD-L1 measured by immunohistochemistry to be frequently expressed in patients with advanced NSCLC. However, PD-L1 expression is not a strong prognostic marker in patients with advanced NSCLC treated with chemotherapy.

PD-L1 expression is a favorable prognostic factor in early stage non-small cell carcinoma

“…High PD-L1 has also been reported to be a favourable prognostic factor in small cell lung carcinomas(43) as well as breast carcinoma (16), colorectal adenocarcinoma (14), gastric cancer(44) and melanoma (23). These results are at odds, however, with two recently presented abstracts on NSCLC (40,45) using the same Merck 22C3 PD-L1 antibody as in our study. One study found high PD-L1 expression was associated with poor overall survival in a Korean population of early and advanced stage NSCLC, particularly in ADCs (40).…”

“…One study found high PD-L1 expression was associated with poor overall survival in a Korean population of early and advanced stage NSCLC, particularly in ADCs (40). In the other study looking at a European population of patients with advanced stage NSCLC M a n u s c r i p t WA Cooper et al 16 treated with chemotherapy, there was no association between PD-L1 expression and overall survival (45). A number of earlier studies found high PD-L1 was associated with a poorer prognosis in NSCLC (8,10,11,40) as well as several other solid human tumors including carcinoma of the pancreas(13), oesophagus (46), liver(47), ovary (17), kidney (19), urothelium (20), and melanoma (21).…”

Lung Cancer Biomarkers

“…Furthermore, IHC PD-L1 positivity in NSCLC has been identified as a potential predictor of response to anti– PD-1 and anti–PD-L1 monoclonal antibody therapy (96) and also as a prognostic biomarker (97). Other studies reported that PD-L1 overexpression cannot be currently considered a robust predictive biomarker for response to immunotherapy or a prognostic biomarker (98). These discrepancies may be due to assay variability and interpretive subjectivity differences for the evaluation of PD-L1 expression, including differences in detection methods, IHC antibody clones, and cut-off values for determining PD-L1 positivity, and heterogeneity in PD-L1 expression and site of PD-L1 expression (tumor cells and tumor inmune cells) (99, 100).…”

Highlights on immune checkpoint inhibitors in non–small cell lung cancer

“…However, when the relationship between PD-L1 expression and OS among chemo-treated patients was evaluated, no obvious association was observed in median or tertile PD-L1 expression levels. 56 Several investigations to ascertain whether polymorphisms of genes involved in immune checkpoints may affect anti-tumor immune activity, thereby influencing clinical outcomes of chemotherapy in NSCLC patients, have been conducted. Lee et al 44 investigated the effects of the genetic polymorphisms of immune checkpoints on patients after first-line chemotherapy.…”