Immune Microenvironment Change After Acquiring Resistance To Egfr Tki Therapy In Egfr Mutant Non-Small Cell Lung Cancer

Introduction: The efficacy of anti-programmed death-1 therapy in EGFR mutant NSCLC is limited. We hypothesized that immune microenvironment was different before and after developing acquired resistance to EGFR-TKI (tyrosine kinase inhibitor) therapy. We evaluated the change of the tumor proportion score (TPS) of programmed death-ligand 1 (PD-L1) and intratumoral CD8 + tumor-infiltrating lymphocyte (TIL) in EGFR mutant NSCLC. Materials and Methods: We identified 44 patients with sufficient paired tumor tissues before and after EGFR-TKI therapy available for analysis. PD-L1 expression on tumor cells was defined by immunohistochemical (IHC) stain with 22C3 pharmDx assay. Intratumoral CD8 + TIL score was also defined by IHC stain. Results: According to paired pre- and post-TKI biopsies comparison, the degree of PD-L1 expression was consistent in both biopsies in 26 (59.1%) patients, but varied upon the development of resistance in 18 (40.9%), with 10 showing higher levels of PD-L1 expression in the resistant biopsy. The score of CD8 + TIL was consistent in both biopsies in 15 (34.1%) patients, but varied upon the development of resistance in 29 (65.9%), with 11 (25%) showing higher levels CD8 + TIL score in the resistant biopsy. Regarding exon 20T790M acquired mutation, only 2 (14.2%) of 14 specimens observed higher TPS of PD-L1 in post-TKI biopsies. We defined high post-TKI TPS of PD-L1 group who observed high TPS of PD-L1 in post-TKI compared to paired pre-TKI biopsies or post- TKI TPS of PD-L1 ≥50%. The post-TKI high TPS of PD-L1 group tended to decrease CD8 + TIL score . 8 observed post-TKI TPS of PD-L1 ≥50% and 7 of 8 observed low CD8 + TIL score. The median progression-free survival of first-generation EGFR-TKI in these 7 patients was statistically significantly lower than the others (6.6 months vs 14.0 months, respectively; P=0.0105). Conclusions: The TPS of PD-L1 and CD8 + TIL score changed after EGFR-TKI therapy. High TPS of PD-L1 and low CD8 + TIL in post-TKI EGFR mutant NSCLC could be related to EGFR-TKI resistance. Before considering anti-PD-1 therapy, reevaluation of PD-L1 should be considered. Citation Format: Tae-Jung Kim, Jin-Hyoung Kang, Sook-hee Hong. Immune microenvironment change after acquiring resistance to EGFR TKI therapy in EGFR mutant non-small cell lung cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B195.