P1.01-106 Clinical Features and Tumor Immune Microenvironment Related to Acquired Resistance to EGFR-TKI in NSCLC Patients with EGFR Mutation

Abstract

First generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) provide significant clinical benefit in advanced non-small cell lung cancer (NSCLC) patients with EGFR mutation. However, patients with initial response to EGFR-TKI ultimately develop acquired resistance to EGFR-TKI treatment, which approximately 50% resistant patients develop second EGFR T790M mutation. New treatment strategy for NSCLC patients harboring EGFR T790M mutation has been available. For those EGFR T790M negative patients, chemotherapy is currently the standard treatment. However, the efficacy of immunotherapy in EGFR T790M mutation NSCLC patients is unknown. Our study focused on the relationship between the clinical features and EGFR T790M mutation status, and the tumor immune microenvironment change before and after acquired resistance to EGFR-TKI in NSCLC patients with EGFR mutation. In this study, we retrospectively evaluated 89 patients with EGFR mutation who received first generation EGFR-TKIs treatment at the First Affiliated Hospital of Zhejiang University between February 2012 and July 2018. All patients were performed second biopsy after acquired resistance to EGFR-TKI. EGFR T790M mutation, epithelial-mesenchymal transition (EMT) and tumor-infiltrating CD4 and CD8 lymphocytes (TILs) in 13 patients with paired biopsy specimens before and after resistance to EGFR-TKI were measured by next generation sequencing (NGS) and immunohistochemistry analyses respectively. Among the 89 eligible patients, EGFR T790M mutation rate was 59.6% (53/89). EGFR T790M mutation was not related with age, gender, smoking status, tumor stage, performance status, but related to the initial EGFR mutation type (EGFR exon 19 deletion or exon 21 L858R mutation). Patients with EGFR exon 19 deletion had significantly higher T790M mutation rate than that with exon 21 L858R mutation (p=0.025). Interestingly, among 11 patients with family cancer history, 10 patients acquired T790M mutation. Furthermore, patients with T790M mutation had longer progression-free survival (PFS) compared to T790M-negative patients (75.5% vs 63.9%, P<0.05). In the small cohort of 13 patients, 6 patients developed EMT after acquired resistance. TILs according to the CD4+ and CD8+ lymphocyte density were not significantly changed in all 13 patients before and after acquired resistance. Our findings indicate that patients with EGFR exon 19 deletion, longer PFS or family cancer history may have higher possibility to develop second EGFR T790M mutation after resistance to EGFR-TKI treatment. The incidence of EMT was higher than we expected, providing further research and clinical treatment ideas. There is no change in TILs after resistance to EGFR-TKI in patients with or without EGFR T790M mutation, but this need further study due to the limited samples in this study.