P1.01-60 Prognostic Impact of PD-L1 Expression on EGFR Tyrosine Kinase Inhibition in Lung Adenocarcinoma

Abstract

EGFR tyrosine kinase inhibitors (TKIs) are recommended as first-line systemic therapy for advanced non-small cell lung cancer (NSCLC) with sensitizing EGFR mutations. The programmed death-ligand 1 (PD-L1) expression on tumor cells has emerged as a prognostic marker after surgical resection in various tumors including NSCLC. This study investigated the predictive value of PD-L1 expression on the duration of treatment and the emergence of T790M mutation in patients treated with EGFR-TKIs. We retrospectively enrolled 109 patients with advanced NSCLC who had been treated with EGFR-TKIs as first-line systemic treatment at Seoul National University Bundang Hospital and Seoul National University Hospital between December 2012 and October 2018. Patients without sensitizing EGFR gene mutations (exon 19 deletion, exon 21 L858R, and L861Q) were excluded. The PD-L1 expression on tumor cells was scored using two immunohistochemistry assays (22C3 or SP263). The Kaplan-Meier survival estimation and log rank test were used for survival analyses. Among the 109 patients (Median age 65; Male:Female = 37:72), 17 (15.6%), 37 (33.9%) and 55 (50.5%) patients had strong (≥50%), weak (1%-49%), and negative (<1%) PD-L1 expression, respectively. In univariate analysis, the median time-to-treatment failure (TTF) of EGFR-TKI treatment was 7.6 months in strong expression, 14.2 months in weak expression, and 13.0 months in negative expression (log-rank; Strong vs. Weak, P=0.008; Strong vs. Negative, P=0.031). There was no statistically significant difference of TTF between the patients with weak expression and negative expression (log-rank, p=0.191). After adjustment of age, sex, and smoking status, strong PD-L1 expression remained as a significant predictor of short TTF (hazard ratio [HR] for strong vs. weak, 2.68; 95% CI, 1.35-5.33; P=0.005). The detection rates of T790M mutation after EGFR-TKI failure were similar in three groups (23.53% in strong, 29.73% in weak, and 32.73% in negative PD-L1 expression; P=0.478). In patients treated with 3rd generation EGFR-TKIs (n=35), there was no statistically significant difference of TTF according to PD-L1 expression (p=0.889). Figure. Kaplan-Meier survival curve for TTF of 1st line EGFR-TKIs according to PD-L1 expression Strong PD-L1 expression of tumor might be a surrogate indicator of poor response to EGFR-TKIs in NSCLC patients with sensitizing EGFR mutations.