LAUSR

Introduction: It has demonstrated that gut microbiome could affect the response to anti-programmed death 1 (PD-1) immunotherapy in the Western population. And one study has suggested that the diversity of gut microbiome was associated with responses to immunotherapy in China. However, there were some conflicts in these previous studies. This study is aimed to further explore the relationship between gut microbiome and clinical response in advanced non-small cell lung cancer (NSCLC) patients. Methods: From 30th/January/2018, advanced NSCLC patients with anti-PD-1 immunotherapy were enrolled. Fecal samples were collected prior to starting therapy and serially after immunotherapy. Total DNA was extracted and 16S ribosome RNA gene sequencing was applied to assess gut microbiome composition. Results: Clinical response rate was determined by radiography according to Response Evaluation Criteria in Solid Tumor Version 1.1. There were sixteen responders (referred to as R, thirteen with stable disease and three with partial response), and thirteen non-responders (NR), yielding a response rate of 55.2%. Firmicutes, Bacteroidetes, Actinobacteria and Proteobacoteria were the main microbial composition in baseline stool samples. Gut microbiome diversity at baseline was not statistically different between responders and non-responders. However, the relative abundance of Akkermansia genus at baseline was significantly enriched in R cohort (p=0.0363). The count of OTUs at progression increased significantly during the treatment. (p=0.012). Of note, Alloprevotellal and Capnocytophaga were overrepresented significantly at progression, indicating that they were associated with unfavorable clinical outcome. Conclusions: This study illustrated that the relationship between clinical outcomes and gut microbiome by dynamic monitoring. Akkermansia present at baseline feces was related with better clinical response to immunotherapy. The increase of some bacteria abundance, especially Alloprevotellal and Capnocytophaga, may predict disease progression during the immunotherapy. This study will continue to collect fecal samples and further verify these conclusions. Citation Format: Lu Yang, Huihui Yin, Yan Wang, Yuchen Jiao. Gut microbiome predicts response to immunotherapy in advanced NSCLC [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6098.