Gut microbiome predicts efficacy and immune-related toxicities of advanced non-small cell lung cancer patients treated with anti-PD-1/PD-L1 Ab-based immunotherapy

The gut microbiome (GM) plays an important role in shaping systemic immune responses. Preclinical and clinical data suggest that GM influences anti-PD-1/PD-L1 or -CTLA-4 Ab-mediated anti-cancer responses. Furthermore, there is strong evidence that antibiotics (ATB) worsen clinical outcomes based on multiple retrospective and one prospective studies using immune checkpoint inhibition (ICI). However, whether GM profiling, at baseline or post-ATB, could represent a biomarker of response in advanced non-small cell lung cancer (NSCLC) during ICI therapy remains unknown. Moreover, the relationship between specific gut microbiota and incidence of immune-related adverse events (irAEs) remain to be precisely elucidated. The objective of the present study was to characterize the impact of ATB on specific GM signatures using metagenomics sequencing in a cohort of 70 patients with advanced NSCLC treated with anti-PD-1/anti-PD-L-1. Primary endpoints were to define specific gut microbiota associated with response and non-response, progression-free survival (PFS), overall survival (OS), and irAEs in both patients who received ATB and those who did not receive ATB.