Abstract 3805: Intestinal microbiome with chemotherapy response and RAS mutation in patients with advanced or metastatic colorectal cancer: a pilot, exploratory study

Abstract Intestinal microbiomes interact with the tumor microenvironment, participating in inflammation and immune regulation, and are associated with the response to anticancer therapy. However, there has been limited research exploring the relationship between changes in the microbiome and treatment response in patients with metastatic colorectal cancer (mCRC) during chemotherapy and radiation therapy. This study included all 15 patients with mCRC treated with first-line systemic therapy between October 2021 and February 2023. We conducted 16S rRNA sequencing on baseline stool samples and investigated the association of intestinal microbiome with chemotherapy response and RAS mutation. The QIIME2 and R packages were used for analysis. As a results, Median age was 61 years (range, 35-73), and there were 8 patients with RAS-mutated mCRC. All patients were treated with first-line systemic therapy; FOLFOX (5-fluorouracil and oxaliplatin) -based (n=13) and FOLFIRI (5-fluorouracil and irinotecan) -based chemotherapy (n=2). Of them, 2 patients received short-course radiotherapy (ScRTx) to primary tumor before systemic chemotherapy, where pre- and post-ScRTx stool samples were collected. Among 15 patients, 9 patients (60%) achieved responses. Non-responders tend to exhibit higher alpha diversity (Chao1, Observed ASV) compared to responders. Firmicutes, Lactobacillus, Faecalibacterium, and the Luminococcusgauvreauiigroup were more prevalent in responders, whereas Bacteroidota, Prevotella, DTU089, Alistipes, ChristensenellaceaeR-7group, and Porphyromonas in non-responders. Despite no statistical significance, alpha diversity decreased in post-ScRTx compared to pre-ScRTx samples. Akkermansia, Prevotella, and Peptostreptococcus were more prevalent in the post-ScRTx compared to pre-ScRTx samples. Regarding the association of intestinal microbiome with RAS mutation, Bray curtis and weighted unifrac analyses revealed significant differences in beta diversity; higher incidence of Faecalibacterium, Lactobacillus, Prevotella, Anaerofilum, and UCG-005 in the RAS-wild type mCRC, while Bacteroides, Collinsella, Holdemanella, and Anaerostipes in RAS-mutated mCRC. This pilot study suggests the prognostic value of gut microbiomes and its association with RAS mutation in patients with mCRC treated with first line systemic therapy. A microbial functional study with immune cytokine change is planned to confirm these findings in future. Citation Format: Jwa Hoon Kim, Boyeon Kim, Soohyeon Lee. Intestinal microbiome with chemotherapy response and RAS mutation in patients with advanced or metastatic colorectal cancer: a pilot, exploratory study abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 3805.