EMERGING evidence suggests that gut microbiota composition may influence the efficacy and safety of chemo-immunotherapy in advanced non-small cell lung cancer (NSCLC), offering a potential biomarker for optimising treatment selection.
A Phase III trial (JCOG2007, NIPPON) assessed the impact of gut microbiota on treatment outcomes in patients receiving pembrolizumab plus platinum doublet chemotherapy or nivolumab-ipilimumab plus platinum doublet chemotherapy (NIC). Baseline faecal samples from 270 of the 295 enrolled patients were analysed using 16S rDNA sequencing to evaluate microbial diversity and differential bacterial abundance.
Beta diversity analysis revealed distinct gut microbiota compositions between patients with overall survival beyond 12 and 18 months. LEfSe analysis identified Fusicatenibacter, Butyricicoccus, and Blautia as enriched in patients with extended survival. Lower microbial alpha diversity and specific bacterial taxa correlated with an increased risk of serious (≥ Grade 4) adverse events, while favourable genera, including Fusicatenibacter and Butyricicoccus, were associated with reduced risk.
Regimen-specific analysis showed that higher levels of Fusicatenibacter and Butyricicoccus correlated with improved survival in the nivolumab-ipilimumab combination arm (hazard ratio: 0.56 and 0.52, respectively). In contrast, increased abundance of Prevotellaceae NK3B31 was linked to higher mortality in the same regimen (hazard ratio: 2.33).
These findings suggest that gut microbiota profiling could refine treatment strategies for advanced lung cancer by predicting both efficacy and safety outcomes in chemo-immunotherapy regimens.
Ada Enesco, EMJ
Reference
Hakozaki T et al. Gut microbiota in advanced non-small-cell lung cancer receiving chemo-immunotherapy: an ancillary biomarker study from the phase III trial JCOG2007 (NIPPON). J Thorac Oncol. 2025;DOI:10.1016/j.jtho.2025.02.026.
