P2.03b-075 PD-1 Protein Expression Predicts Survival in Resected Adenocarcinomas of the Lung: Topic: Biomarkers

Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) have demonstrated clinical activity in patients with advanced non-small cell lung carcinoma (NSCLC). The ability of PD-1 and PD-L1 immunohistochemistry (IHC) to predict benefit of immune checkpoint inhibitors remains controversial. We assessed the prognostic value of PD-1 and PD-L1 IHC in patients with completely resected adenocarcinoma of the lung. We determined protein expression of PD-1 and PD-L1 in formalin-fixed paraffin-embedded surgical specimens of 161 NSCLC patients with adenocarcinoma histology by IHC. We used the EH33 antibody (Cell Signaling) for PD-1 and the E1L3N antibody (Cell Signaling) for PD-L1 IHC. Cut-points of ≥1% PD-1-positive immune cells at any staining intensity and ≥1% PD-L1-positive tumor cells at any staining intensity were correlated with clinicopathological features and patient survival. Positive PD-1 immunostaining in immune cells was observed in 71 of 159 (45%) evaluable tumor samples. PD-1 positive staining was not significantly associated with any of the clinicopathological features. Positive PD-1 immunostaining was associated with longer recurrence-free and overall survival of the patients. Multivariate Cox proportional hazards regression analyses identified PD-1 to be an independent prognostic factor for recurrence (adjusted hazard ratio [HR] for recurrence 0.58; 95% confidence interval [CI] 0.36 to 0.94; P = 0.026) and death (adjusted HR for death 0.46; 95% CI 0.26 to 0.82; P = 0.008). PD-L1 positive staining in tumor cells was seen in 59 of 161 (37%) cases. Positive PD-L1 immunostaining correlated with KRAS mutation (P = 0.019) and type of surgery (P = 0.01) but was not significantly associated with any of the other clinicopathological parameters. Positive PD-L1 immunostaining was not associated with survival of the patients (adjusted HR for recurrence 0.92; 95% CI 0.58 to 1.47; P = 0.733; adjusted HR for death 0.61; 95% CI 0.34 to 1.07; P = 0.084). Positive PD-1 but not PD-L1 immunostaining is a favorable independent prognostic factor in patients with completely resected adenocarcinoma of the lung.