The Significance Of PD-L1 Expression In A Cohort Of Patientswith EGRF Mutation-positive Lung Adenocarcinoma

Objective:To explore the clinical significance of PD-L1 expression in patients with lung adenocarcinoma bearing EGFR mutations. Methods:1. A total of 56 patients with EGFR mutation-positive advanced lung adenocarcinoma who have then had received the EGFR-TKI therapy(gefitinib or erlotinib) were collected, between April 2010 and July 2014 at Fuzhou General Hospital.2. EGFR gene mutations in exons 18, 19, 20, and/or 21 were examined in tumor samples obtained from biopsy or surgical resection, using the amplification refractory mutation system(ARMS) and the fluorescence polymerase-chain-reaction(PCR) diagnostic kit.3. Immunohistochemistry was performed to evaluate expression of PD-1, PD-L1, CD4+ and CD8+ tumor-infiltrating T lymphocytes(TILs).4. Objective response rate(ORR) and DCR were measured according to Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1. Patients’ PFS and OS were calculated.5. Relationship between PD-L1 expression and various clinicopathologic parameters was analyzed using the χ2 test. The Kaplan-Meier method was used to estimate survival probability, and the log-rank test used to determine statistical significance. The multivariate analysis using the Cox regression model was conducted to analyze the clinicopathologic features. All tests were two-sided. P < 0.05 was considered as statistically significant. Statistical analyses were done using a SPSS software package(version 19.0). Results:1. In a cohort of 56 patients, PD-L1 and PD-1 were positive in 53.6% and 32.1% tumor specimens, respectively.2. Expression of either PD-L1 or PD-1 did not correlate with various clinical characteristics of patients in this cohort, including age at diagnosis, gender, smoking, ECOG performance status when receive EGFR-TKIs, prior chemotherapy, tumor grade(differentiation), and brain metastases(P > 0.05 for all cases). However, there was a significant correlation between PD-1 and Ki-67 expression, for which Ki-67 >15% had higher PD-1 expression, compared to Ki-67 ≤ 15%(P = 0.005).3. No significant correlation between PD-L1 expression and CD4+ or CD8+ TIL scores was found in patients with EGFR-mutation-positive NSCLC(P > 0.05 for each case).4. The DCR of patients(n = 30) with PD-L1-positive tumors was significantly higher than those(n = 26) with PD-L1-negative tumors(93.3%, 28/30 versus 61.5%, 16/26; P = 0.004), while no statistical significance observed for the difference in ORR(36.7%, 11/30 versus 15.4%, 4/26; P = 0.073).5. PD-L1-positive patients displayed significantly higher disease-control rate(DCR, P = 0.004), after the TKI therapy, as well as longer progression-free survival(PFS, P = 0.001) and overall survival(OS, P = 0.004), while no correlation between PD-1 positivity and clinical outcomes was observed.Conclusions:The subtype of EGFR-mutation-positive NSCLC is highly eligible for PD-1/PD-L1 immunotherapy. PD-L1 might represent a favorable biomarker candidate for response to EGFR-TKIs and outcome of these NSCLC patients.