Pd-L1 Expression and Survival Among Advanced Non–Small Cell Lung Cancer (Nsclc) Patients Treated with Chemotherapy

Abstract

ABSTRACT Aim: Recent clinical trial results suggest programmed cell death ligand-1 (PD-L1) expression measured by immunohistochemistry (IHC) may predict response to anti-PD-1 therapy. There are inconsistent results on whether PD-L1 expression is associated with survival among patients with advanced NSCLC treated with chemotherapy. Methods: We evaluated the relationship between PD-L1 expression and overall survival (OS) among 204 advanced NSCLC patients treated at Aarhus University Hospital from 2007 to 2012. PD-L1 expression was measured using a prototype IHC assay with the 22C3 antibody. PD-L1-strong and -weak positivity were defined to be traceable to the clinical trial version of the assay. Kaplan-Meier methods, log-rank test, and Cox proportional hazards models were used for survival analysis, adjusting for age, gender, histology, smoking history, and performance status. Results: Median (range) age was 65 years (33-86), 55% were female, 22% had squamous cell carcinoma, and 88% were stage IV. All patients received chemotherapy as initial therapy, including 83% treated with carboplatin/vinorelbine, 15% with carboplatin/vinorelbine/bevacizumab, and 2% with others; 32% of patients also received radiotherapy with initial therapy. Twenty-five percent of patients were PD-L1-strong–positive, and 50% were PD-L1-weak–positive. There was no statistically significant association between PD-L1 expression and survival, with an adjusted hazard ratio (AHR) of 1.34 (95% CI, 0.88-2.03; median OS, 9.0 mo) for the PD-L1-strong–positive group and 1.07 (95% CI, 0.74-1.55; median OS, 9.8 mo) for the PD-L1-weak–positive group when compared with the PD-L1-negative group (median OS, 7.5 mo). There was no association between PD-L1 expression and OS when PD-L1 expression levels were stratified by the median or tertiles. Conclusions: Using a preliminary IHC assay and cutoff, the results did not suggest that PD-L1 expression is a strong prognostic marker among advanced NSCLC patients treated with chemotherapy. The inconsistent results observed in previous studies may be due to different antibodies, cutoff values, or patient population characteristics. Disclosure: W. Zhou: Full-time employment at Merck & Co., Inc., with stock ownership; M. Dolled-Filhart: Full-time employment at Merck & Co., Inc.; J.B. Georgsen: Corporate sponsored research–Merck Sharp & Dohme; Z. Wang: Full-time employment–Merck Sharp & Dohme; K. Emancipator: Full-time employment–Merck & Co., Inc.; D. Wu: Full-time employment at Merck & Co., Inc., with stock ownership; M. Busch-Sorensen: Full-time employment–Merck & Co., Inc. All other authors have declared no conflicts of interest.