1037P Tumour mutational burden and HLA diversity by TruSight oncology 500 (TSO500) next generation sequencing panel and clinical outcome in non-small cell lung cancer

Abstract

Background: The microbiota community is considered as an organ of the human body. Recent studies have found that gut microbiota may impact on the interaction between immune regulation and tumor treatment. The aim of this study is to characterize the gut microbiota in advanced NSCLC patients, and its relationship with response to immune checkpoint blockade (ICB). Methods: Stool samples from 84 advanced NSCLC patients were collected prior ICB as first or second line treatment. 16S rRNA gene sequencing and SILVA_release_132 database were used for taxonomic profiling. Diversity indices, including Chao1, Shannon and Inverse Simpson index (IDI), abundance of certain taxa, clinicopatho-logical characteristics, dietary habits and antibiotic usage were evaluated for association with clinical benefit (CB) [complete or partial response, stable disease vs. progressive disease (PD), according to RECIST1.1]. Continuous variables were stratified into high or low using median as cutoff. For survival analysis, Cox Regression and Kaplan Meier curves with log-rank test were performed. Results: From 84 NSCLC patients, 60 presented PD-L1 positive tumors and 39 were treated with ICB as first line. A total of 8872307 sequencing reads were obtained and clustered in 357 genera, being the most frequent Bacteroides (27.9%) and Alistipes (7.1%). Patients with CB exhibited higher IDI compared with those with PD (p¼0.004). Moreover, higher IDI was associated with prolonged progression-free survival (PFS) (p¼0.014). High abundance of Butyricimonas in the samples was correlated with increased RR (p¼0.01) and longer PFS (p¼0.011) compared to low abundance. On the other hand, high frequency of Dialister was associated with reduced RR (p¼0.002) and shorter PFS (p¼0.003). Finally, the expression of PD-L1 was associated with increased response rate (RR) (p¼0.020). Conclusions: This study shows that diversity of gut microbiota is related to the ICB treatment response. In addition, high abundance of Butyricimonas and low abundance of Dialister could be considered as potential predictors of clinical benefit and PFS. Further analyses are being undertaken to find a compositional signature with predictive value. Funded by CB16/12/00350 from CIBEROnc, Arnal Planelles Foundation , AMACMA, GIDO group and PI18/00226 from ISCIII. Background: This study investigated the role of programmed death-ligand 1 (PD-L1) expression in the sex-related differences in immune checkpoint inhibitor (ICI) efficacy. Methods: We first pooled individual patient-level data from prospective clinical trials to evaluate ICI efficacy between male and female stratified by PD-L1 expression. We further combined individual patient-level data with meta-analysis of randomized controlled trials (RCTs) to assess the efficacy of ICI versus chemotherapy in each of the sexes. Finally, we assessed sex associated with landscape of tumor microenvironment among PD-L1 expression-negative patients. Results: In total, 1,594 patients were included from five clinical trials, and nine RCTs with 4,718 patients were included in meta-analysis. Among patients with PD-L1 expression<1%, individual patient-level analysis showed that overall survival (OS) with ICI was significantly longer for female compared with male (HR 0.58, 95% CI 0.42-0.80; P<.001). The OS benefit of ICI over chemotherapy was significantly different in female (HR 0.57, 95% CI 0.38-0.85; P¼.006), but not in male. Among patients with PD-L1 expression1%, individual patient-level analysis combined with meta-analysis showed that the OS benefit of ICI over chemotherapy was significantly different in male (HR 0.76, 95% CI 0.67-0.85; P<.01), both in first-line patients (HR 0.79, 95% CI 0.65-0.97; P¼0.02) and subsequent-line patients (HR 0.73, 95% CI 0.62-0.85; P<.01); however, this benefit for female was only significant in subsequent-line patients (HR 0.77, 95% CI 0.62-0.96; P¼.02). Additionally, the central memory T cell was potentially correlated with the OS differences between the sexes at PD-L1 expression<1%. Conclusions: The association of sex with OS benefits of ICIs in cancer were greatly influenced by PD-L1 expression. At PD-L1 expression<1%, ICI should be recommended for female but not for male. At PD-L1 expression1%, ICI should be recommended for male regardless of treatment lines; whereas for female, ICI could be only recommended in subsequent-line setting. Sex and PD-L1 expression should be jointly considered in the clinical decision making for ICI in cancer. Legal entity responsible for the study: Herui Yao. Funding: Has not received any funding. Background: TMB predicts response to PD-1 immunotherapy (IO). High HLA class I diversity correlates with better responses in NSCLC. Standard to determine TMB and HLA diversity, is WES. We describe the correlation between TMB and HLA-diversity score by targeted NGS (TSO500) and outcome in immunotherapy treated NSCLC.