Gut microbiome composition and response to sunitinib in metastatic renal cell carcinoma (mRCC).
657 Background: Recent evidence supports a link between stool microbiome composition and immunotherapy response. However, it is unclear how the microbiome may influence clinical outcome in mRCC where vascular endothelial growth factor-targeted therapies remains a standard of care. Methods: Five consecutive stool samples were collected at baseline and at weeks 2, 3, 4 and 12 of treatment with sunitinib in patients (pts) with mRCC. In responders (R: complete/partial response and stable disease) and non-responders (P: primary progression), gut microbiota composition was assessed through extraction of microbial DNA where 16s RNA gene tags (v4) were generated by PCR amplification and sequenced using MiSeq (Illumina). Sequence reads were processed by Mothur software, assembled in Operational Taxonomic Units (OTUs), taxonomically annotated to the genus level, and used to construct Bray-Curtis dissimilarity matrix. The similarity of samples was visualized by principle coordinate (PCo) analysis and further confirmed by k-means clustering and ANOSIM tests. Differentially abundant taxa were determined by METASTATS. Results: Stool bacteriomic profiling identified 25,304 OTUs attributable to 165 genera from 8 phyla in 4 of 6 pts evaluable for response. PCo analysis revealed clear separation of R and P (accounting for 28.9 % of dataset variation) where subsequent k-means clustering confirmed the difference of microbiota in 2 clusters that perfectly align with R and P groups. The significance of this separation was confirmed by ANOSIM analysis (p = 0.005). Analysis of microbiota composition in P and R groups revealed 14 differentially abundant taxonomic units at the genus level. Of those at ≥1% abundance, Bacteroides, Barnesiella and Phascolarctobacterium were elevated in R, while Bifidobacterium and Dorea were elevated in P (p < 0.01 for all). Of those at < 1% abundance, Lactococcus, Sporobacter, Acidaminococcus, Actinomyces, and Asaccharobacter were elevated in P (p < 0.01 for all). Conclusions: Although limited by sample size, we report the first in-human study to suggest a link between microbiota and response to sunitinib as we identified a significant discrepancy in stool bacteriomic distribution between P and R.