Contribution of the microbiome to differential drug efficacy and clinical trial outcomes between the US and Japan
Abstract
3086 Background: The gut microbiome is a source of patient variation that influences the efficacy of anticancer drugs (Spanogiannopoulos et al., 2022) . The microbiome also varies at a population level (Pasolli et al., 2019) .There is a limited understanding of the impact of this variation. We show for the first time that differences in drug-microbiome interactions may translate to differential clinical trial outcomes. For extensive-stage, small cell lung cancer (SCLC), irinotecan-cisplatin is a first-line treatment in Japan, based on data from Japan Clinical Oncology Group (JCOG) 9511 (Noda et al., 2002) demonstrating superior efficacy to etoposide-cisplatin (RR 87% vs 68%; PFS 12.8 vs 9.4 months). Despite employing an identical study design, the Southwest Oncology Group (SWOG) 0124 (Lara et al., 2009) failed to confirm this benefit for a US population. The reasons for this discrepancy are unclear. Methods: Microbiome analysis was performed using BioCorteX’s industry-leading knowledge graph and integrated proprietary engines v20231108_220940. 56,171 stool microbiome samples from the US adult population and 3,558 stool samples from the Japanese adult population were included. A database built on existing literature was used to identify proteins produced by organisms in these samples. These microbial-derived proteins were analysed for sequence similarity to human proteins that interact with irinotecan, etoposide and cisplatin. Interactions were ranked by the abundance of…
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