P52.02 High SHP2 Expression Determines the Efficacy of PD-1/PD-L1 Inhibitors in Advanced KRAS Mutant Non-Small Cell Lung Cancer

Src homology region 2 domain-containing phosphatase 2 (SHP2) is a novel target for KRAS mutant cancer but the clinical effect of SHP2 remain largely unknown. We retrospectively studied the predictive significance of SHP2 in KRAS mutant NSCLC treated with immune checkpoint inhibitor (ICI). Advanced KRAS mutant NSCLC patients who underwent immunotherapy were enrolled. Next-generation sequencing (NGS) was used to profile mutation status of the tumors. The expression of SHP2 and programmed death ligand 1 (PD-L1) was analyzed by immunohistochemistry (IHC). Treatment responses were assessed by specialists according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. 61 advanced KRAS mutant NSCLC patients treated with immunotherapy were enrolled. SHP2 was heterogeneously expressed in 32 samples and highly expressed (H-score>10) in 25 (78.1%) samples. Patients with high SHP2 expression made up 100.0% of the partial response (PR) and 80.0% of the stable disease (SD), while 50.0% of the progress disease (PD). High expression level of SHP2 was associated with longer progression-free survival (PFS) and overall survival (OS) (P < 0.001, P = 0.013). Patients with high expression of both SHP2 and PD-L1 had a longer PFS (P < 0.001).View Large Image Figure ViewerDownload Hi-res image Download (PPT) High expression of SHP2 could predict the efficacy of ICI and better survival in advanced KRAS mutant NSCLC patients.