Impact of EGFR mutation on the clinical efficacy of PD-1 inhibitors in patients with pulmonary adenocarcinoma.

Abstract

We evaluated the predictive role of EGFR mutation on the efficacy of PD-1/PD-L1 inhibitor therapy in patients with advanced pulmonary adenocarcinoma while considering clinical factors such as PD-L1 expression, gender, and smoking status. Patients were required to have available data for EGFR mutation, PD-L1 expression, and efficacy of PD-1/PD-L1 inhibitors. Among 178 patients with EGFR-mutant (n = 38) or wild-type (WT) (n = 140) tumors, the EGFR mutation group had a lower objective response rate (ORR) (15.8% vs. 32.9%, p = 0.04) than the EGFR WT group, similar to the pattern observed for other factors: weak/negative PD-L1 expression vs. strong PD-L1 expression (17.3% vs. 39.2%, p = 0.001); never smokers vs. smokers (19.4% vs. 35.1%, p = 0.03); and females vs. males (21.0% vs. 33.6%, p = 0.08). EGFR mutation and weak/negative PD-L1 expression were associated with a significantly shorter median PFS than EGFR WT (1.9 vs. 3.0months, p = 0.04) and strong PD-L1 expression (1.6 vs. 3.9months, p = 0.007), respectively. In multivariate analysis, EGFR mutation predicted worse ORR [hazard ratio (HR) 3.15; 95% confidence interval (CI) 1.15-8.63] and PFS (HR 1.75, 95% CI 1.11-2.75), as did weak/negative PD-L1 expression (ORR, HR 3.46, 95% CI 1.62-7.37; and PFS, HR 1.72, 95% CI 1.17-2.53). Together with PD-L1 expression, EGFR mutation status is an important factor to predict the efficacy of PD-1/PD-L1 inhibitors in patients with pulmonary adenocarcinoma.